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.

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

Cold preservation with hyperbranched polyglycerol-based solution improves kidney functional recovery with less injury at reperfusion in rats

PubMed Central

Li, Shadan; Liu, Bin; Guan, Qiunong; Chafeeva, Irina; Brooks, Donald E; Nguan, Christopher YC; Kizhakkedathu, Jayachandran N; Du, Caigan

2017-01-01

Minimizing donor organ injury during cold preservation (including cold perfusion and storage) is the first step to prevent transplant failure. We recently reported the advantages of hyperbranched polyglycerol (HPG) as a novel substitute for hydroxyethyl starch in UW solution for both cold heart preservation and cold kidney perfusion. This study evaluated the functional recovery of the kidney at reperfusion after cold preservation with HPG solution. The impact of HPG solution compared to conventional UW and HTK solutions on tissue weight and cell survival at 4°C was examined using rat kidney tissues and cultured human umbilical vein endothelial cells (HUVECs), respectively. The kidney protection by HPG solution was tested in a rat model of cold kidney ischemia-reperfusion injury, and was evaluated by histology and kidney function. Here, we showed that preservation with HPG solution prevented cell death in cultured HUVECs and edema formation in kidney tissues at 4°C similar to UW solution, whereas HTK solution was less effective. In rat model of cold ischemia-reperfusion injury, the kidneys perfused and subsequently stored 1-hour with cold HPG solution showed less leukocyte infiltration, less tubular damage and better kidney function (lower levels of serum creatinine and blood urea nitrogen) at 48 h of reperfusion than those treated with UW or HTK solution. In conclusion, our data show the superiority of HPG solution to UW or HTK solution in the cold perfusion and storage of rat kidneys, suggesting that the HPG solution may be a promising candidate for improved donor kidney preservation prior to transplantation. PMID:28337272

[Skin necrosis resulting from the extravasation of intravenous injections].

PubMed

Ikhefoulma, Soumaya; Mahiou, Abelhamid; Perillat, Isabelle

2012-09-01

Extravasation is the diffusion of a product injected intravenously into the perivascular or subcutaneous spaces. Skin necrosis of iatrogenic origin can be observed for example with a subcutaneous perfusion of solution containing potassium chloride or the extravasation of 30% hypertonic glucose serum. Whenever a product is injected, the administration route for which the product has obtained marketing authorisation must be respected and a perfusion time of at least 4 to 5 hours per litre of solution perfused must be observed.

Preparation of Kupffer cell enriched non-parenchymal liver cells with high yield and reduced damage of surface markers by a modified method for flow cytometry.

PubMed

Xu, Fan; Zhen, Peng; Zheng, Yu; LIjuan, Feng; Aiting, Yang; Min, Cong; Hong, You; Jidong, Jia

2013-04-01

The aim of this study was to optimise a collagenase perfusion protocol for the isolation of a liver non-parenchymal cell (NPC) suspension enriched for Kupffer cells that reduced damage to F4/80 antigen cell surface expression to allow analysis by flow cytometry. Kupffer cell-enriched liver NPCs were isolated from C57BL/6 mice using different protocols. Flow cytometry was used to examine the effect of collagenase digestion on F4/80 expression on Kupffer cells, and results were represented by the percentage of F4/80 positive cells and by the F4/80 mean fluorescence intensity (MFI). The perfusion temperature, concentration of collagenase solution and total dosage of collagenase for liver perfusion influenced the effect of collagenase perfusion on the expression of F4/80 antigen on Kupffer cells. Collagenase perfusion at 28°C resulted in an increased percentage of F4/80 positive cells (P = 0.001) and MFI (P = 0.005) compared with 37°C. Perfusion with a total dose of 1.0 g/kg BW collagenase (using a 0.75 mg/mL solution) resulted in the highest percentage of F4/80 positive cells (P = 0.001) compared with 0.8 g/kg BW and 1.2 g/kg BW collagenase. Isolation of cells using the modified protocol resulted in a higher percentage of Kupffer cells (P < 0.001) and a higher MFI of F4/80 antigen (P < 0.001) compared with the common protocol. © 2013 International Federation for Cell Biology.

Modification of Rat Lung Decellularization Protocol Based on Dynamic Conductometry of Working Solution.

PubMed

Kuevda, E V; Gubareva, E A; Gumenyuk, I S; Sotnichenko, A S; Gilevich, I V; Nakokhov, R Z; Rusinova, T V; Yudina, T G; Red'ko, A N; Alekseenko, S N

2017-03-01

We modified the protocol of obtaining of biological scaffolds of rat lungs based on dynamic recording of specific resistivity of working detergent solution (conductometry) during perfusion decellularization. Termination of sodium deoxycholate exposure after attaining ionic equilibrium plateau did not impair the quality of decellularization and preserved structural matrix components, which was confirmed by morphological analysis and quantitative assay of residual DNA.

HOCl causes airway substance P hyperresponsiveness and neutral endopeptidase hypoactivity.

PubMed

Murlas, C G; Murphy, T P; Lang, Z

1990-06-01

We investigated whether exposure of guinea pig tracheal tissue to hypochlorous acid (HOCl) or hydrogen peroxide (H2O2) by perfusion through the airway lumen affected the responsiveness of airway muscle to ACh, KCl, or substance P in the presence or absence of 1 microM phosphoramidon, an inhibitor of neutral endopeptidase (NEP). Pairs of tracheal segments were immersed in a Krebs solution (pH 7.40 at 37 degrees C) and connected to perfusion circuits so that the lumen of one segment of each pair could be perfused with Krebs solution while the other was perfused for the same time (10 min) with either 0.1 microM HOCl or 10 mM H2O2. Segments after perfusion were cut into rings of similar size and placed in muscle chambers so that airway muscle force generation in vitro could be measured on stimulation by cumulative agonist doses. In addition, cell homogenates were made from other, similarly perfused tracheal segments to assess NEP activity using reverse-phase, high-pressure liquid chromatography (HPLC). We found that smooth muscle of mucosa-intact guinea pig airways perfused with HOCl, but not H2O2, was hyperresponsive to substance P but not to ACh or KCl. HOCl-perfused rings were not different from Krebs solution-exposed rings pretreated with phosphoramidon. There was no increase in substance P responsiveness of HOCl-exposed airways in which the mucosa had been removed before testing in vitro. The substance P hyperresponsiveness of HOCl-exposed, mucosa-intact airways was associated with decreased NEP activity.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Changes in body temperature of the unanaesthetized monkey produced by sodium and calcium ions perfused through the cerebral ventricles

PubMed Central

Myers, R. D.; Veale, W. L.; Yaksh, T. L.

1971-01-01

1. In the unanaesthetized Rhesus monkey, solutions containing sodium, calcium, potassium or magnesium in excess of the normal concentration of extracellular fluid were perfused from a lateral to the fourth ventricle through chronically implanted cannulae. 2. Sodium (11·0-88·0 mM in excess of the physiological concentration) perfused through the ventricles, caused an immediate rise in body temperature which was accompanied by vasoconstriction, piloerection and shivering. The latency of the hyperthermia was related directly to the rate of perfusion and the concentration of sodium, whereas the magnitude of the response depended upon the concentration only. When the perfusion was terminated, shivering ceased and the temperature of the monkey returned to the base line level. 3. When calcium ions were perfused in concentrations 2·5-47·9 mM in excess of that of extracellular fluid, a fall in the temperature of the animal occurred. The magnitude of the decreases depended upon the concentration of calcium in the perfusion fluid. Vasodilatation, sedation and a reduction in withdrawal reflexes accompanied the calcium-induced hypothermia. After the perfusion ended, the temperature continued to fall until the monkey began to shiver and vasoconstriction was observed in many skin areas. 4. The perfusion through the cerebral ventricles with modified Krebs solution alone or with the Krebs solution which contained potassium or magnesium ions in concentrations five to ten times normal had virtually no effect on the temperature of the monkey. 5. Since the temperature of the monkey was unchanged as long as the physiological ratio of sodium to calcium in the perfusion fluid remained constant, we conclude that the balance between these two essential cations within the brain stem could determine the neural mechanism whereby the set-point for body temperature of the primate is established. PMID:4999638

Responses to the lowering of magnesium and calcium concentrations in the cerebrospinal fluid of unanesthetized sheep.

PubMed

Allsop, T F; Pauli, J V

1975-12-01

A technique for ventriculolumbar perfusion of the cerebrospinal fluid space has been used to study the neuromuscular effects of low concentrations of magnesium and calcium in the cerebrospinal fluid of conscious sheep. Perfusion with synthetic cerebrospinal fluid solutions containing less than 0-6 mg magnesium/100 ml produced episodes of tetany which were abolished by perfusion with a solution of normal magnesium concentration. This suggests that the low cerebrospinal fluid magnesium concentrations reported in cases of hypomagneseamic tetany may result in changes within the central nervous system that could produce the nervous signs. Perfusates with a calcium concentration below 2-0 mg/100 ml caused hyperpnoea and continuous muscle tremors. Magnesium (0-6 mg/100 ml) and calcium (2-0 mg/100 ml) perfused simultaneously acted synergistically to produce signs characteristic of low levels of each of the ions.

Effect of specific antibodies on the excitability of internally perfused squid axons.

PubMed

Huneeus, F C; Fernandez, H L

1967-11-01

Giant axons from the squid Dosidicus gigas were internally perfused with rabbit antiaxoplasm antibodies and their effect upon the action potential and the membrane potential was studied. Necessary requirements for the antibodies to affect these parameters in a consistent manner were: (a) removal of the bulk of axoplasm from the perfused zone, accomplished by initially perfusing with a cysteine-rich (400 mM) solution, and (b) addition of small amounts of cysteine (30 mM) to the antibody-containing solution. When these experimental conditions were met, conduction block ensued generally within 3 hr of the first contact of the axon inner surface with the antibody Antineurofilament antibodies and nonspecific antibodies had no effect. External application of antiaxoplasm antibodies had no effect.

On the mode of action of ACTH on the isolated perfused adrenal gland

PubMed Central

Jaanus, Siret D.; Rosenstein, M. J.; Rubin, R. P.

1970-01-01

1. Isolated cat adrenal glands were perfused with Locke solution, and the corticosteroid outputs in response to adrenocorticotrophin (ACTH) were studied. 2. Steroid outputs varied with the ACTH concentration, as well as with the duration of exposure to a given ACTH concentration. 3. Omission of calcium from the perfusion medium markedly depressed ACTH-evoked steroid release. The steroid output was directly related to the extracellular calcium concentration up to 0·5 mM. 4. During a constant exposure to ACTH, steroid output was maintained for at least 2-3 hr, provided that calcium was present in the perfusion medium. 5. Strontium, but not barium or magnesium, replaced calcium in maintaining the secretory response to ACTH. 6. Magnesium depressed ACTH-evoked secretion in the presence of calcium, and this depression of secretion was antagonized by increasing the calcium concentration. 7. Prolonged perfusion with sodium-free or potassium-free solutions did not markedly inhibit steroid output in response to ACTH. Excess potassium (56 mM) did not produce a consistent or marked increase in spontaneous steroid output and did not affect the response to ACTH. 8. The steroid content of adrenal glands perfused with Locke solution and exposed to ACTH was about 10% of the amount which was secreted. By contrast, adrenal glands perfused with calcium-free media and exposed to ACTH contained much higher amounts of steroid, despite the negligible amount secreted. 9. These data suggest that calcium plays a critical role in the mechanism of corticosteroid secretion from the adrenal cortex. PMID:4322584

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

PubMed

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

2003-03-01

Crotalidae Polyvalent Immune Fab (CroFab; FabAV) antivenom prevents a decrease in perfusion pressures in intramuscular crotaline envenomation compared with normal saline solution. We used a randomized, blinded, controlled acute animal preparation. Twenty anesthetized and instrumented swine were injected intramuscularly with 6 mg/kg Crotalus atrox venom into the anterior tibialis muscle of each hind limb (time 0). One hour after envenomation (time 1 hour), animals were randomized to receive 8 vials of reconstituted FabAV or an equal volume of normal saline solution (control) through a central venous line. The main outcome variable was the area under the perfusion-time curve (AUC) of the anterior compartment of the hind limb measured from time 1 hour to time 8 hours. Perfusion pressure was defined as mean arterial pressure-compartment pressure. Additionally, physiologic variables, including pulse rate, prothrombin time, fibrinogen level, platelet count, hemoglobin level, and hematocrit level, were monitored. Venom injection resulted in a decrease in average perfusion pressures from 54.1 mm Hg (time 0) to 31.7 mm Hg (time 1 hour). Comparison of AUC between groups from time 1 hour (time of treatment) to the completion of the study at time 8 hours revealed a 57% greater AUC in animals that received FabAV (mean+/-SD: 211.1+/-67.9 versus 134.5+/-55.8 mm Hg/h; P =.036; 95% confidence interval for difference 5.9 to 147.3). Comparison of the time curves for the mean prothrombin time from time 1 hour to the completion of the study by means of repeated-measures analysis of variance revealed a significant increase in the control group (P =.02). No significant difference was detected in the time curves for the means of mean arterial pressure, compartment pressure, pulse rate, hemoglobin level, hematocrit level, fibrinogen level, or platelet count over the course of the study. FabAV was found to significantly increase survival time when compared with the effect of the normal saline solution control from time 1 hour to time 8 hours, as determined by means of Kaplan-Meier estimation and the log-rank test (P =.029). FabAV limits the decrease in perfusion pressures in the anterior leg compartment after intramuscular crotaline venom injection in swine compared with saline solution. In addition, FabAV might prevent the development of coagulopathy and increase survival time in this model.

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 ...

Evaluation of a pyridoxylated hemoglobin polyoxyethylene conjugate solution as a perfusate for small intestine preservation.

PubMed

Liu, H; Agishi, T; Kawai, T; Hayashi, T; Fujita, S; Fuchinoue, S; Takahashi, K; Teraoka, S; Ota, K

1992-01-01

A new type of artificial blood, pyridoxylated hemoglobin-polyoxyethylene conjugate (PHP) solution, (developed by PHP research group of the department of health and welfare of Japan, and produced by Ajinomoto Co., Inc. Tokyo) as an oxygen-carrying component, has been recently devised using hemoglobin obtained from hemolyzed human erythrocytes. Recently, the studies using this solution as a preservation solution were performed in some instances. To examine the mechanism of improved viability using this solution as a preservation solution, we developed a model of orthotopic small intestine transplantation (OIT) in the rat. As a baseline study, we compared parameters of viability of the grafts preserved in Collins and UW solution to those preserved in PHP solution including a survival rate, a serum level total protein and albumin, and a change in body weight after transplantation. In our study, the simple hypothermia storage together with intestinal perfusion preservation with PHP solution was performed. Animals were divided into 6, 12, and 24 hr preservation groups. All of the rats survived after 6 hr preservation following transplantation. However, in 12 hr storage, five of six rats in PHP solution preservation survived and recovery in body weight after grafting was better than those with Collins and UW solution. We conclude that the PHP solution is, therefore, considered to possibly be a more suitable perfusate for small intestine preservation than Collins and UW solution.

Numerical solution of non-linear dual-phase-lag bioheat transfer equation within skin tissues.

PubMed

Kumar, Dinesh; Kumar, P; Rai, K N

2017-11-01

This paper deals with numerical modeling and simulation of heat transfer in skin tissues using non-linear dual-phase-lag (DPL) bioheat transfer model under periodic heat flux boundary condition. The blood perfusion is assumed temperature-dependent which results in non-linear DPL bioheat transfer model in order to predict more accurate results. A numerical method of line which is based on finite difference and Runge-Kutta (4,5) schemes, is used to solve the present non-linear problem. Under specific case, the exact solution has been obtained and compared with the present numerical scheme, and we found that those are in good agreement. A comparison based on model selection criterion (AIC) has been made among non-linear DPL models when the variation of blood perfusion rate with temperature is of constant, linear and exponential type with the experimental data and it has been found that non-linear DPL model with exponential variation of blood perfusion rate is closest to the experimental data. In addition, it is found that due to absence of phase-lag phenomena in Pennes bioheat transfer model, it achieves steady state more quickly and always predict higher temperature than thermal and DPL non-linear models. The effect of coefficient of blood perfusion rate, dimensionless heating frequency and Kirchoff number on dimensionless temperature distribution has also been analyzed. The whole analysis is presented in dimensionless form. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluation of chloride/bicarbonate. Exchange in the human colon in vivo.

PubMed Central

Davis, G R; Morawski, S G; Santa Ana, C A; Fordtran, J S

1983-01-01

During perfusion of a plasma-like solution, colonic absorption rate of chloride was much higher than the secretion rate of bicarbonate (34 vs. 3.5 meq/h, respectively). This might suggest that anion exchange (Cl/HCO3) accounts for only a small fraction of total chloride absorption. However, if the colon absorbs as well as secretes bicarbonate, this reasoning would underestimate the magnitude of the anion exchange. To see if the colon absorbs bicarbonate, we perfused a chloride-free solution (which would eliminate bicarbonate secretion via (Cl/HCO3 exchange) and found that the colon absorbed bicarbonate at a rate of 5.1 meq/h. Calculation of electrochemical gradients and measurement of luminal fluid PCO2 indicated that this bicarbonate absorption was mediated passively in response to electrical gradients, rather than via reversed Cl/HCO3 exchange or acid secretion. The combined results of the plasma-like and chloride-free perfusion experiments suggest Cl/HCO3 exchange at a rate of 8.6 meq/h (the sum of bicarbonate movements, 3.5 and 5.1 meq/h, observed in the two experiments). To obtain a second estimate under different experimental conditions, a choline chloride-choline bicarbonate (sodium-free) solution was perfused; with this solution, chloride and bicarbonate absorption dependent on active sodium transport should be eliminated or markedly reduced, and the magnitude of Cl/HCO3 exchange should be revealed. This experiment suggested a Cl/HCO3 exchange rate of 9.3 meq/h, similar to the first estimate. As chloride was absorbed at a rate of 34 meq/h during perfusion of the plasma-like solution, the Cl/HCO3 exchange provides for approximately one-fourth of total chloride absorption. PMID:6401766

Evaluation of chloride/bicarbonate. Exchange in the human colon in vivo.

PubMed

Davis, G R; Morawski, S G; Santa Ana, C A; Fordtran, J S

1983-02-01

During perfusion of a plasma-like solution, colonic absorption rate of chloride was much higher than the secretion rate of bicarbonate (34 vs. 3.5 meq/h, respectively). This might suggest that anion exchange (Cl/HCO3) accounts for only a small fraction of total chloride absorption. However, if the colon absorbs as well as secretes bicarbonate, this reasoning would underestimate the magnitude of the anion exchange. To see if the colon absorbs bicarbonate, we perfused a chloride-free solution (which would eliminate bicarbonate secretion via (Cl/HCO3 exchange) and found that the colon absorbed bicarbonate at a rate of 5.1 meq/h. Calculation of electrochemical gradients and measurement of luminal fluid PCO2 indicated that this bicarbonate absorption was mediated passively in response to electrical gradients, rather than via reversed Cl/HCO3 exchange or acid secretion. The combined results of the plasma-like and chloride-free perfusion experiments suggest Cl/HCO3 exchange at a rate of 8.6 meq/h (the sum of bicarbonate movements, 3.5 and 5.1 meq/h, observed in the two experiments). To obtain a second estimate under different experimental conditions, a choline chloride-choline bicarbonate (sodium-free) solution was perfused; with this solution, chloride and bicarbonate absorption dependent on active sodium transport should be eliminated or markedly reduced, and the magnitude of Cl/HCO3 exchange should be revealed. This experiment suggested a Cl/HCO3 exchange rate of 9.3 meq/h, similar to the first estimate. As chloride was absorbed at a rate of 34 meq/h during perfusion of the plasma-like solution, the Cl/HCO3 exchange provides for approximately one-fourth of total chloride absorption.

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.

Assessing viability of extracorporeal preserved muscle transplants using external field stimulation: a novel tool to improve methods prolonging bridge-to-transplantation time

PubMed Central

Taeger, Christian D.; Friedrich, Oliver; Dragu, Adrian; Weigand, Annika; Hobe, Frieder; Drechsler, Caroline; Geppert, Carol I.; Arkudas, Andreas; Münch, Frank; Buchholz, Rainer; Pollmann, Charlotte; Schramm, Axel; Birkholz, Torsten; Horch, Raymund E.; Präbst, Konstantin

2015-01-01

Preventing ischemia-related cell damage is a priority when preserving tissue for transplantation. Perfusion protocols have been established for a variety of applications and proven to be superior to procedures used in clinical routine. Extracorporeal perfusion of muscle tissue though cumbersome is highly desirable since it is highly susceptible to ischemia-related damage. To show the efficacy of different perfusion protocols external field stimulation can be used to immediately visualize improvement or deterioration of the tissue during active and running perfusion protocols. This method has been used to show the superiority of extracorporeal perfusion using porcine rectus abdominis muscles perfused with heparinized saline solution. Perfused muscles showed statistically significant higher ability to exert force compared to nonperfused ones. These findings can be confirmed using Annexin V as marker for cell damage, perfusion of muscle tissue limits damage significantly compared to nonperfused tissue. The combination of extracorporeal perfusion and external field stimulation may improve organ conservation research. PMID:26145230

Ion Fluxes and Short-Circuit Current in Internally Perfused Cells of Valonia ventricosa

PubMed Central

Gutknecht, John

1967-01-01

Ion transport in the giant celled marine alga, Valonia ventricosa, was studied during internal perfusion and short-circuiting of the vacuole potential. The perfusing and bathing solutions were similar to natural Valonia sap and contained the following concentrations of major ions: Na 51, K 618, and Cl 652 mM. The average short-circuit current (I sc) was 97 pEq/cm2 sec (inward positive current), and the average open-circuit potential difference (PD) was 74 mv (vacuole positive to external solution). Perfused and short-circuited cells showed a small net influx of Na (2.0 pEq/cm2 sec) and large net influxes of K (80 pEq/cm2 sec) and Cl (50 pEq/cm2 sec). Unidirectional K influx was proportional to I sc, but more than one-half of the I sc remained unaccounted for. Both the I sc and PD were partly light-dependent, declining rapidly during the first 1–2 min of darkness. Ouabain (5 x 10-4 M) had little effect on the influx of Na or K and had no effect on I inf or PD. Fluid was absorbed at a rate of about 93 pliter/cm2 sec. Reversing the direction of fluid movement by adding mannitol to the outside solution had little effect on ion movements. The ionic and electrical properties of normal and perfused cells of Valonia are compared. PMID:6050968

Vascular perfusion of reproductive organs in pony mares and heifers during sedation with detomidine or xylazine.

PubMed

Araujo, Reno R; Ginther, O J

2009-01-01

To assess the vascular effects of detomidine and xylazine in pony mares and heifers, respectively, as determined in a major artery and by extent of vascular perfusion of reproductive organs. 10 pony mares and 10 Holstein heifers. Pony mares were assigned to receive physiologic saline (0.9% NaCl) solution (n = 5) or detomidine (3.0 mg/mare, IV; 5). Heifers were assigned to receive saline solution (5) or xylazine (14 mg/heifer, IM; 5). Color Doppler ultrasonographic examinations were performed immediately before and 10 minutes after administration of saline solution or sedative. In spectral Doppler mode, a spectral graph of blood flow velocities during a cardiac cycle was obtained at the internal iliac artery and at the ovarian pedicle. In color-flow mode, color signals of blood flow in vessels of the corpus luteum and endometrium were assessed. Systemic effects of sedation in the 2 species were evident as a decrease in heart rate; increase in duration of systole, diastole, or both; decrease in volume of blood flow; and decrease in velocity of blood flow within the internal iliac artery. However, an effect of sedatives on local vascular perfusion in the ovaries and endometrium was not detected. Sedation with detomidine in pony mares and xylazine in heifers did not affect vascular perfusion in reproductive organs. These sedatives can be used in experimental and clinical color Doppler evaluations of vascular perfusion of the corpus luteum and endometrium.

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.

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

PubMed

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

2014-01-01

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

Capacity Planning for Batch and Perfusion Bioprocesses Across Multiple Biopharmaceutical Facilities

PubMed Central

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

2014-01-01

Production planning for biopharmaceutical portfolios becomes more complex when products switch between fed-batch and continuous perfusion culture processes. This article describes the development of a discrete-time mixed integer linear programming (MILP) model to optimize capacity plans for multiple biopharmaceutical products, with either batch or perfusion bioprocesses, across multiple facilities to meet quarterly demands. The model comprised specific features to account for products with fed-batch or perfusion culture processes such as sequence-dependent changeover times, continuous culture constraints, and decoupled upstream and downstream operations that permit independent scheduling of each. Strategic inventory levels were accounted for by applying cost penalties when they were not met. A rolling time horizon methodology was utilized in conjunction with the MILP model and was shown to obtain solutions with greater optimality in less computational time than the full-scale model. The model was applied to an industrial case study to illustrate how the framework aids decisions regarding outsourcing capacity to third party manufacturers or building new facilities. The impact of variations on key parameters such as demand or titres on the optimal production plans and costs was captured. The analysis identified the critical ratio of in-house to contract manufacturing organization (CMO) manufacturing costs that led the optimization results to favor building a future facility over using a CMO. The tool predicted that if titres were higher than expected then the optimal solution would allocate more production to in-house facilities, where manufacturing costs were lower. Utilization graphs indicated when capacity expansion should be considered. © 2013 The Authors Biotechnology Progress published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers Biotechnol. Prog., 30:594–606, 2014 PMID:24376262

The Effect of Polyhexanide, Octenidine Dihydrochloride, and Tea Tree Oil as Topical Antiseptic Agents on In Vivo Microcirculation of the Human Skin: A Noninvasive Quantitative Analysis.

PubMed

Rothenberger, Jens; Krauss, Sabrina; Tschumi, Christian; Rahmanian-Schwarz, Afshin; Schaller, Hans-Eberhard; Held, Manuel

2016-10-01

Antiseptics are indispensable for wound management and should focus not only on the efficacy in reducing the bacterial burden but also on how much they interfere in wound healing. In this study, the authors analyzed the direct effect of topical antiseptic agents on the microcirculation of intact human skin. The perfusion dynamics were assessed before, and 10 minutes after, the volunteers' fingers of the right hand (n = 20) were immersed in the following solutions - octenidine dihydrochloride, polyhexanide, tea tree oil, and saline solution. The authors used the Oxygen to See (LEA Medizintechnik GmbH, Giessen, Germany) diagnostic device for noninvasive determination of oxygen supply in microcirculation of blood perfused tissues, which combines a laser light to determine blood flow, as well as white light to determine hemoglobin oxygenation and the relative amount of hemoglobin. Tea tree oil (÷19.0%) (B. Braun Melsungen AG, Melsungen, Germany) and polyhexanide (÷12.4%) (Lavanid, Serag Wiessner GmbH, Naila, Germany) caused a significant increase in blood flow compared to the negative control (-25.6%). Octenidine (Octenisept, Schülke & Mayr GmbH, Norderstedt, Germany) showed a nonsignificant trend towards an increase in blood flow (÷7.2%). There were alterations in the values of hemoglobin oxygenation and the relative amount of hemoglobin, but these were not significant. Perfusion is an important factor for wound healing. Therefore, it might be advantageous if antiseptic agents would increase blood flow. Tea tree oil and polyhexanide have a positive effect on skin blood flow and can therefore be used especially in critically perfused wounds, provided the adverse reactions and the antimicrobial efficacy are comparable.

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.

Detection of myocardial ischemia by automated, motion-corrected, color-encoded perfusion maps compared with visual analysis of adenosine stress cardiovascular magnetic resonance imaging at 3 T: a pilot study.

PubMed

Doesch, Christina; Papavassiliu, Theano; Michaely, Henrik J; Attenberger, Ulrike I; Glielmi, Christopher; Süselbeck, Tim; Fink, Christian; Borggrefe, Martin; Schoenberg, Stefan O

2013-09-01

The purpose of this study was to compare automated, motion-corrected, color-encoded (AMC) perfusion maps with qualitative visual analysis of adenosine stress cardiovascular magnetic resonance imaging for detection of flow-limiting stenoses. Myocardial perfusion measurements applying the standard adenosine stress imaging protocol and a saturation-recovery temporal generalized autocalibrating partially parallel acquisition (t-GRAPPA) turbo fast low angle shot (Turbo FLASH) magnetic resonance imaging sequence were performed in 25 patients using a 3.0-T MAGNETOM Skyra (Siemens Healthcare Sector, Erlangen, Germany). Perfusion studies were analyzed using AMC perfusion maps and qualitative visual analysis. Angiographically detected coronary artery (CA) stenoses greater than 75% or 50% or more with a myocardial perfusion reserve index less than 1.5 were considered as hemodynamically relevant. Diagnostic performance and time requirement for both methods were compared. Interobserver and intraobserver reliability were also assessed. A total of 29 CA stenoses were included in the analysis. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for detection of ischemia on a per-patient basis were comparable using the AMC perfusion maps compared to visual analysis. On a per-CA territory basis, the attribution of an ischemia to the respective vessel was facilitated using the AMC perfusion maps. Interobserver and intraobserver reliability were better for the AMC perfusion maps (concordance correlation coefficient, 0.94 and 0.93, respectively) compared to visual analysis (concordance correlation coefficient, 0.73 and 0.79, respectively). In addition, in comparison to visual analysis, the AMC perfusion maps were able to significantly reduce analysis time from 7.7 (3.1) to 3.2 (1.9) minutes (P < 0.0001). The AMC perfusion maps yielded a diagnostic performance on a per-patient and on a per-CA territory basis comparable with the visual analysis. Furthermore, this approach demonstrated higher interobserver and intraobserver reliability as well as a better time efficiency when compared to visual analysis.

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.

PROTOPLASMIC POTENTIALS IN HALICYSTIS

PubMed Central

Blinks, L. R.

1935-01-01

Perfusion of the vacuole of living cells of Halicystis is described, the method employing two longitudinally fused capillaries as entrance and exit tubes. Natural sap, artificial sap, and sea water have been successfully perfused, with various additions and deficiencies, within the limits of physiological balance. In H. ovalis the P.D. remains positive and scarcely reduced in value when normal sea water, at pH 8.1, is perfused in the vacuole. In H. Osterhoutii the P.D. reverses in sign when the perfused solution has a higher pH than 6.5. In both cases a large P.D. persists when the solutions are the same on both sides of the protoplasm. In the absence of external gradients, there must be some internal gradient or asymmetry of the protoplasm itself to account for the P.D. Since appreciable currents are produced, there must be some metabolic activity as a source of energy. The higher normal P.D. in H. ovalis is not due to the higher KCl content of its sap (as earlier suggested by the author) since it persists nearly unchanged when sea water is substituted for sap. PMID:19872853

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

Jejunal and ileal absorption of oxprenolol in man: influence of nutrients and digestive secretions on jejunal absorption and systemic availability.

PubMed Central

Godbillon, J; Vidon, N; Palma, R; Pfeiffer, A; Franchisseur, C; Bovet, M; Gosset, G; Bernier, J J; Hirtz, J

1987-01-01

1 Study I evaluated the absorption of oxprenolol in the ileum, compared to jejunum, in healthy volunteers by an intestinal perfusion technique. Around 80 mg of drug were delivered as a saline solution directly in the small bowel. 2 Samples taken 30 cm distally to the site of perfusion showed that 63% of perfused oxprenolol was absorbed in the jejunum and 48% in the ileum; the differences were significant. 3 The plasma concentration-time profiles were similar for the two perfusions. The AUC and Cmax values of free and conjugated oxprenolol for the jejunal perfusion were significantly lower than those of ileum. They showed large but consistent intersubject variations in the two treatments. 4 Study II investigated, using the same technique, the influence of nutrients and digestive secretions on jejunal absorption and systemic availability of this drug. A saline (in treatments A and B) or a nutrient (in treatment C) solution containing oxprenolol was perfused into the jejunum below a balloon either inflated (A) or deflated (B and C). 5 The disappearance rate of oxprenolol from the jejunum was unaffected by endogenous secretions. The mean amount of drug absorbed along a 30-cm jejunal segment accounted for 52 (A) and 57% (B) of the total amount perfused. The intestinal absorption rate was markedly increased in the presence of nutrients (mean amount absorbed 96% for C). 6 The change in the rate of disappearance from the intestine had no effect on the systemic availability of oxprenolol (mean AUC values 8740, 8250 and 8020 nmol l-1 h for A, B and C, respectively) or its elimination from plasma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3663450

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

Controlled destruction and temperature distributions in biological tissues subjected to monoactive electrocoagulation.

PubMed

Erez, A; Shitzer, A

1980-02-01

An analysis of the temperature fields developed in a biological tissue undergoing a monoactive electrical coagulating process is presented, including thermal recovery following prolonged heating. The analysis is performed for the passage of alternating current and assumes a homogeneous and isotropic tissue model which is uniformly perfused by blood at arterial temperature. Solution for the one-dimensional spherical geometry is obtained by a Laplace transform and numerical integrations. Results obtained indicate the major role which blood perfusion plays in determining the effects of the coagulating process; tissue temperatures and depth of destruction are drastically reduced as blood perfusion increases. Metabolic heat generation rate is found to have negligible effects on tissue temperatures whereas electrode thermal inertia affects temperature levels appreciably. However, electrodes employed in practice would have a low thermal inertia which might be regarded as zero for all practical purposes. It is also found that the depth of tissue destruction is almost directly proportional to the electrical power and duration of application. To avoid excessively high temperatures and charring, it would be advantageous to reduce power and increase the time of application. Results of this study should be regarded as a first approximation to the rather complex phenomena associated with electrocoagulation. They may, nevertheless, serve as preliminary guidelines to practicing surgeons applying this technique.

Improved Recovery of Hepatocytes Isolated From Warm Ischemic Rat Liver by Citrate Phosphate Dextrose (CPD)-Supplemented Euro-Collins Solution

PubMed Central

Hsu, Huai-Che; Matsuno, Naoto; Machida, Noboru; Enosawa, Shin

2013-01-01

Demand for human primary hepatocytes is increasing, particularly for clinical trials of hepatocyte transplantation. However, due to the severe shortage of organ transplant donors, the source of cells for these endeavors is restricted to untransplantable livers, such as those from non-heart-beating donors and surgically resected liver tissues. To improve cell recovery from such sources after warm ischemia, we evaluated the efficacy of applying perfusion solutions, focusing on improvement of hepatocyte recovery. Warm ischemia was induced by clamping both portal vein and hepatic artery for 10 or 15 min in rats. The liver was perfused with either Euro-Collins (EC) or extracellular-type trehalose-containing Kyoto (ETK) solutions supplemented with an anticoagulant, either heparin or citrate phosphate dextrose solution (CPD), compared to Ca2+, Mg2+-free Hanks solution. While the viability of recovered cells was 81.5 ± 4.2% and cell yield was 2.27 ± 0.53 × 108 in nonwarm ischemia controls (n = 11), these values were only 74.7 ± 2.9% and 0.38 ± 0.17 × 108, respectively, in the 10-min warm ischemia group, using the Hanks as the perfusion solution. Although the addition of heparin increased the live cell number only twofold (0.71 ± 0.40 × 108, n = 4), the best improvement was achieved by adding CPD to EC. This resulted in a recovery of 1.41 ± 0.50 × 108 in the 10-min ischemia group (n = 7) and 1.37 ± 0.28 × 108 in the 15-min group (n = 3). Macroscopic observation showed that blood had been completely flushed out by the solution, suggesting good restoration of the microcirculation in ischemic liver. Using ETK instead of EC resulted in a slight decrease in efficacy. These results demonstrate that CPD, as opposed to heparin, is effective in ensuring liver microcirculation and flushing out the blood and that EC is the best perfusion solution for obtaining hepatocytes from ischemic liver. PMID:26858872

[Effect of hypertonic-hyperoncotic solution infusion on tissue perfusion during surgical treatment of the abdominal aorta].

PubMed

Soskić, Ljiljana; Davidović, Lazar; Milicić, Biljana; Kocica, Mladen; Kovacević, Natasa; Simić, Tijana

2007-10-01

Decreasing of arterial flow below the critical level leads to capillary endothelium edema and to further worsening of tissue perfusion. Hypertonic solution infusion provides mild and short plasma osmolality increasing, while colloidal solutions intensify that effect. The aim of this study was to investigate the effect of hypertonic-hyperoncotic solution (HH) on the organs perfusion during reconstructive surgical procedure on the abdominal aorta (AA). The study included 40 patients submitted to AA reconstruction due to aneurysm or Leriche's syndrome. A clamp was put transversally to the aorta, under the outlets of the renal arterias. According to the solution received when a clamp was on the aorta, the patients were divided into two groups containing 20 patients each: the tested group (A) which received 4 ml/kg of the solution (7.2% NaCl/10% dextran), and the control group (B) which received 0.9% NaCl. The study excluded the patients with the preoperative creatinine level more than 139 micromol/l, and ejection heart fraction less than 40%. The mixed venous blood oxygen saturation increased from 73.3+/-7.33 to 74.95+/-6.19% in the group A, while it decreased from 65.35+/-10.39 to 62.65+/-10.42% in the group B (p = 0.001). The quantity of the provided oxygen in the group A increased significantly from 684.44+/-244.34 to 1362.45+/-2351.01 ml/min, while it decreased from 668.2+/-382.12 to 651.7+/-313.98 ml/min in the group B (p = 0.016). Alveolo-arterial difference in oxygen decreased from 23.12+/-14.74 to 21.1+/-10 mmHg in the group A, while it increased from 23.79+/-15.22 to 26.33+/-13.78 mmHg in the group B (p = 0.05). Satisfactory perfusion of organs during the AA surgery is obtained by using both HH and an isotonic solution. Due to maintaining the optimal values of the minute heart volume, saturation of vein blood blended with oxygen, and al-veolo-arterial difference in oxygen, it is recommended to use HH solution for reanimation of patients in declamping shock.

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.

Effects of saliva from chronically reserpinized rat on Na and K transport in perfused main excretory duct of submandibular gland of normal rat.

PubMed

Jirakulsomchok, D; Schneyer, C A

1987-09-01

Reserpine (RES) (0.5 mg/kg body wt, ip) was administered to rats for 7 days. On Day 8 saliva was evoked from these animals by intraperitoneal injection of pilocarpine nitrate (10 mg/kg body wt) and saliva from submandibular and parotid glands was collected separately. These collected salivas were used to perfuse through the main ducts of the submandibular glands of normal rats. After a control period of perfusion of the main duct with bicarbonate saline solution, parotid saliva from RES rats was perfused through the duct followed by regular perfusion. There was inhibition of Na absorption (22%) and K secretion (23%). Moreover, when submandibular saliva from treated rat was perfused through the main duct prior to regular perfusion, there was a decrease in Na absorption (31%) and K secretion (28%). In contrast, perfusion of the main duct with either parotid or submandibular saliva from normal rats caused no significant changes in Na and K transport. The present experiments confirm previous studies that there is some Na-inhibitory factor(s) present in saliva of the chronically RES-treated rat.

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.

Cardiotonic action of two tannins

PubMed Central

Broadbent, J. L.

1962-01-01

A tannin isolated from Paullinia pinnata Linn., and tannic acid, have cardiotonic actions on the isolated perfused frog heart. Paullinia tannin is more firmly “fixed” than tannic acid. Tannin solutions contain peroxide, but the cardiotonic action is not dependent on this, since drugs believed to prevent peroxide formation, and sodium pyruvate which destroys peroxides, do not prevent the cardiotonic action. Maximal stimulation by tannin greatly reduces subsequent stimulation by ouabain. If calcium is omitted from the Ringer solution tannins cannot stimulate the heart. In this respect they differ from ouabain. However, the ouabain stimulation can be prevented by prior perfusion with tannin. It is suggested that the antagonism between tannin and ouabain is due to the former preventing ouabain from reaching its receptor sites, and that tannin stimulation is dependent on the formation of a calcium-tannin complex at the heart surface. In the isolated perfused mammalian heart preparation tannins increase diastolic tonus and coronary flow. PMID:13873207

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.

Biolasol: novel perfusion and preservation solution for kidneys.

PubMed

Cierpka, L; Ryszka, F; Dolińska, B; Smorąg, Z; Słomski, R; Wiaderkiewicz, R; Caban, A; Budziński, G; Oczkowicz, G; Wieczorek, J

2014-10-01

Biolasol solution (Pharmaceutical Research and Production Plant "Biochefa," Sosnowiec, Poland) is a novel extracellular perfusion and ex vivo hypothermic kidney preservation solution. It ensures maintenance of homeostasis, reduces tissue edema, has low viscosity, and allows the graft to preserve structural and functional integrity. It minimizes ischemia-reperfusion damage. Perfundates from control and transplanted kidneys flushed with Biolasol or ViaSpan solutions (Arkas, Warszawa, Poland) were analyzed. Parameters of serum and urine collected from 12 pigs after auto-transplantation were also analyzed. Renal medulla was investigated for structural alterations by analyzing hematoxylin and eosin-stained slides. The mean survival time of pigs after the auto-transplantation procedure was the measure for the novel Biolasol solution effectiveness. We observed a statistically significant decrease in marker enzyme levels alanine transaminase, aspartate transaminase, lactic dehydrogenase, and ions (Na and K) in pigs with grafts flushed with Biolasol. Histopathologic examination revealed that the renal cortex structure was not damaged after the use of Biolasol solution. Biolasol solution protects kidneys against ischemia damage and does not differ significantly from the "golden standard" ViaSpan solution.

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.

Performance assessment of an opto-fluidic phantom mimicking porcine liver parenchyma

NASA Astrophysics Data System (ADS)

Akl, Tony J.; King, Travis J.; Long, Ruiqi; McShane, Michael J.; Nance Ericson, M.; Wilson, Mark A.; Coté, Gerard L.

2012-07-01

An implantable, optical oxygenation and perfusion sensor to monitor liver transplants during the two-week period following the transplant procedure is currently being developed. In order to minimize the number of animal experiments required for this research, a phantom that mimics the optical, anatomical, and physiologic flow properties of liver parenchyma is being developed as well. In this work, the suitability of this phantom for liver parenchyma perfusion research was evaluated by direct comparison of phantom perfusion data with data collected from in vivo porcine studies, both using the same prototype perfusion sensor. In vitro perfusion and occlusion experiments were performed on a single-layer and on a three-layer phantom perfused with a dye solution possessing the absorption properties of oxygenated hemoglobin. While both phantoms exhibited response patterns similar to the liver parenchyma, the signal measured from the multilayer phantom was three times higher than the single layer phantom and approximately 21 percent more sensitive to in vitro changes in perfusion. Although the multilayer phantom replicated the in vivo flow patterns more closely, the data suggests that both phantoms can be used in vitro to facilitate sensor design.

Demonstration of the production of oxygen-centered free radicals during electrolysis using E.S.R. spin-trapping techniques: effects on cardiac function in the isolated rat heart.

PubMed

Lecour, S; Baouali, A B; Maupoil, V; Chahine, R; Abadie, C; Javouhey-Donzel, A; Rochette, L; Nadeau, R

1998-03-01

The present study was designed to identify the free radicals generated during the electrolysis of the solution used to perfuse isolated rat heart Langendorff preparations. The high reactivity and very short half-life of oxygen free radicals make their detection and identification difficult. A diamagnetic organic molecule (spin trap) can be used to react with a specific radical to produce a more stable secondary radical or "spin adduct" detected by electron spin resonance (ESR). Isovolumic left ventricular systolic pressure (LVSP) and left ventricular end diastolic pressure (LVEDP) were measured by a fluid-filled latex balloon inserted into the left ventricle. The coronary flow was measured by effluent collection. Electrolysis was performed with constant currents of 0.5, 1, 1.5, 3, 5, 7.5, and 10 mA generated by a Grass stimulator and applied to the perfusion solution for 1 min. A group of experiments was done using a 1.5 mA current and a Krebs-Henseleit (K-H) solution containing free radical scavengers (superoxide dismutase (SOD): 100 IU/ml or mannitol: 50 mM). Heart function rapidly declined in hearts perfused with K-H buffer that had been electrolyzed for 1 min. The addition of mannitol (50 mM) to the perfusion solution had no effect on baseline cardiac function before electrolysis while SOD (100 IU/ml) increased the coronary flow. However, SOD was more effective than the mannitol in protecting the heart against decreased of cardiac function, 5 min after the end of electrolysis. Samples of the K-H medium subjected to electrolysis were collected in cuvettes containing a final concentration of 125 mM 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and analyzed by spectroscopy. The ESR spectrum consisted of a quartet signal (hyperfine couplings aN = aH = 14.9 G) originating from the hydroxyl adduct signal, DMPO-OH. The intensity of the DMPO-OH signal remained stable during the 60 s of electrolysis and the quantity of free radicals induced by electrolysis was directly proportional to the intensity of the current. The addition of mannitol and SOD to the perfusate scavenged the hydroxyl radicals present in the solution, suggesting that both hydroxyl and superoxide radicals were formed during electrolysis.

Analysis of the Effects of Calcium or Magnesium on Voltage-Clamp Currents in Perfused Squid Axons Bathed in Solutions of High Potassium

PubMed Central

Rojas, Eduardo; Taylor, Robert E.; Atwater, Illani; Bezanilla, Francisco

1969-01-01

Isolated axons from the squid, Dosidicus gigas, were internally perfused with potassium fluoride solutions. Membrane currents were measured following step changes of membrane potential in a voltage-clamp arrangement with external isosmotic solution changes in the order: potassium-free artificial seawater; potassium chloride; potassium chloride containing 10, 25, 40 or 50, mM calcium or magnesium; and potassium-free artificial seawater. The following results suggest that the currents measured under voltage clamp with potassium outside and inside can be separated into two components and that one of them, the predominant one, is carried through the potassium system. (a) Outward currents in isosmotic potassium were strongly and reversibly reduced by tetraethylammonium chloride. (b) Without calcium or magnesium a progressive increase in the nontime-dependent component of the currents (leakage) occurred. (c) The restoration of calcium or magnesium within 15–30 min decreases this leakage. (d) With 50 mM divalent ions the steady-state current-voltage curve was nonlinear with negative resistance as observed in intact axons in isosmotic potassium. (e) The time-dependent components of the membrane currents were not clearly affected by calcium or magnesium. These results show a strong dependence of the leakage currents on external calcium or magnesium concentration but provide no support for the involvement of calcium or magnesium in the kinetics of the potassium system. PMID:5823216

Analysis of the effects of calcium or magnesium on voltage-clamp currents in perfused squid axons bathed in solutions of high potassium.

PubMed

Rojas, E; Taylor, R E; Atwater, I; Bezanilla, F

1969-10-01

Isolated axons from the squid, Dosidicus gigas, were internally perfused with potassium fluoride solutions. Membrane currents were measured following step changes of membrane potential in a voltage-clamp arrangement with external isosmotic solution changes in the order: potassium-free artificial seawater; potassium chloride; potassium chloride containing 10, 25, 40 or 50, mM calcium or magnesium; and potassium-free artificial seawater. The following results suggest that the currents measured under voltage clamp with potassium outside and inside can be separated into two components and that one of them, the predominant one, is carried through the potassium system. (a) Outward currents in isosmotic potassium were strongly and reversibly reduced by tetraethylammonium chloride. (b) Without calcium or magnesium a progressive increase in the nontime-dependent component of the currents (leakage) occurred. (c) The restoration of calcium or magnesium within 15-30 min decreases this leakage. (d) With 50 mM divalent ions the steady-state current-voltage curve was nonlinear with negative resistance as observed in intact axons in isosmotic potassium. (e) The time-dependent components of the membrane currents were not clearly affected by calcium or magnesium. These results show a strong dependence of the leakage currents on external calcium or magnesium concentration but provide no support for the involvement of calcium or magnesium in the kinetics of the potassium system.

Fibrinolytic preflush upon liver retrieval from non-heart beating donors to enhance postpreservation viability and energetic recovery upon reperfusion.

PubMed

Minor, T; Hachenberg, A; Tolba, R; Pauleit, D; Akbar, S

2001-06-27

Our objective was to evaluate graft equilibration with high viscosity (University of Wisconsin solution [UW]) or low viscosity (Bretschneider's histidine-tryptophan-ketoglutarate [HTK]) during liver procurement from non-heart beating donors (NHBD) and the potential impact of a preceding fibrinolysis with streptokinase on postpreservation viability. After 60 min of cardiac arrest, rat livers were perfused by gravity (60 cm H2O) via the portal vein with either 60 ml of HTK, 20 ml of UW, or 20 ml of Ringer's solution (22 degrees C including 7500U of streptokinase) and, subsequently, 20 ml of UW. After 24 h of storage at 4 degrees C, viability of the livers was assessed upon isolated reperfusion in vitro. Magnetic resonance imaging revealed severe perfusion deficits, which were mildly attenuated with HTK, upon flush-out with UW. After preflush with streptokinase, a mostly homogenous distribution of the preservation solution was observed throughout the liver tissue. The choice of the flush-out solution (UW or HTK) had no influence on parenchymal enzyme leakage, hepatic bile production, or tissue levels of ATP after reperfusion of the livers. Fibrinolytic preflush, however, resulted in a relevant and significant improvement of structural integrity as well as functional and metabolic recovery. Compromised vascular tissue perfusion upon organ harvest in NHBD triggers graft dysfunction after cold storage and can easily be circumvented by temporary fibrinolysis before graft retrieval.

Hypothermic in situ perfusion of the porcine liver using Celsior or Ringer-lactate solution.

PubMed

Dinant, S; Roseboom, H J; Levi, M; van Vliet, A K; van Gulik, T M

2009-01-01

Hypothermic perfusion (HP) of the liver is applied during total vascular exclusion (TVE) to reduce ischemic injury during liver resection. No studies have been performed comparing different perfusion solutions for HP. The aim of this experimental study was to compare Ringer-lactate solution (RL) with Celsior solution (Cs) for HP in a pig model of 60-min TVE. Twenty pigs underwent 60-min TVE of the liver. Groups were TVE without HP (no-HP, n = 9), TVE with HP using RL (n = 6), and TVE with HP using Cs (n = 5). Blood and liver tissue samples were taken before TVE and during 24-h reperfusion. In the no-HP group, plasma aspartate aminotransferase values were significantly increased during reperfusion (p < 0.05), while liver tissue pO(2) levels (p < 0.01) were decreased when compared to the HP groups. After 24-h reperfusion, bile production and liver tissue glutathione content were significantly higher (p < 0.05) in the Cs group (42.0 +/- 1.7 mL/h and 44.9 +/- 2.2 nmol/mg, respectively) as compared to the RL group (31.5 +/- 3.5 mL/h and 19.6 +/- 1.8 nmol/mg, respectively). The protective effect of HP during TVE was confirmed in this study. HP with Cs was more effective in reducing ischemic injury as compared to HP with RL.

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

Effect of dimethylaminoethanol, an inhibitor of betaine production, on the disposition of choline in the rat kidney

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

Lohr, J.; Acara, M.

1990-01-01

The choline metabolite betaine has been shown to be an important organic osmoregulatory solute in the kidney. The isolated perfused rat kidney and kidney slice incubations were used to investigate the effect of 2-dimethylaminoethanol (DMAE), a choline oxidase inhibitor, on the renal excretion and metabolism of choline. In the isolated perfused kidney, ({sup 14}C)choline, at an initial perfusate concentration of 300 microM, was effectively removed from the perfusate over 25 min, with nearly all the {sup 14}C in the perfusate accounted for by betaine during the remainder of the 90-min perfusion. DMAE at concentrations of 3.0 or 5.0 mM significantlymore » decreased the rate of removal of ({sup 14}C)choline from the perfusate and the rate of addition of ({sup 14}C)betaine to the perfusate, yet (14C)betaine remained the only metabolite of choline in perfusate and urine. In kidney tissue slice experiments, conversion of ({sup 14}C)choline to ({sup 14}C)betaine was found in cortical, outer medullary and inner medullary regions of rat kidney. DMAE at 5.0 mM significantly inhibited ({sup 14}C)betaine production in each of the three regions studied. These data show that DMAE is an effective inhibitor of betaine production by the kidney and, as such, may be an important agent for the study of osmoregulation by the kidney.« less

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 established risk factors, potentially representing an important step forward in the translation of quantitative CMR perfusion analysis to the clinical setting. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

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.

Lubiprostone stimulates small intestinal mucin release

PubMed Central

2012-01-01

Background Lubiprostone is a synthetic bicyclic fatty acid derivative of prostaglandin E1 (PGE1) used for chronic constipation. The best known action of lubiprostone is simulation of Cl- dependent fluid secretion. In a mouse model of the genetic disease cystic fibrosis, we previously showed that in vivo administration of lubiprostone resulted in greater mucus accumulation in the small intestine. The aim of this study was to directly test whether lubiprostone stimulates intestinal mucin release. Methods Mucin release was measured by mounting segments (4-5 cm) of mouse proximal-mid small intestine in an organ bath, allowing access to the perfusate (luminal) and the bath (serosal) solutions. Nifedipine (10-6 M) and indomethacin (10-5 M) were included in all solutions to inhibit smooth muscle activity and endogenous prostaglandin production, respectively. The tissue was equilibrated under flow for 30 min, using the perfusate collected during the final 10 min of the equilibration period to measure unstimulated release rate. Stimulus was then added to either the perfusate or the bath and the perfusate was collected for another 30 min to measure the stimulated mucin release rate. Mucin in perfusates was quantified by periodic acid-Schiff's base dot-blot assay, using purified pig gastric mucin as a standard. Results When applied luminally at 1 μM lubiprostone was ineffective at stimulating mucin release. When added to the serosal solution, 1 μM lubiprostone stimulated mucin release to ~300% of the unstimulated rate. As a positive control, serosal 1 μM prostaglandin E2 increased mucin release to ~400% of the unstimulated rate. Conclusions These results support the idea that lubiprostone has prostaglandin-like actions on the intestine, which includes stimulation of mucin release. Stimulation of mucin release by lubiprostone may be protective in gastrointestinal conditions where loss of mucus is believed to contribute to pathogenesis. Thus, in addition to chronic constipation, there is greater potential for the therapeutic applications of lubiprostone. PMID:23130661

Lubiprostone stimulates small intestinal mucin release.

PubMed

De Lisle, Robert C

2012-11-06

Lubiprostone is a synthetic bicyclic fatty acid derivative of prostaglandin E1 (PGE1) used for chronic constipation. The best known action of lubiprostone is simulation of Cl- dependent fluid secretion. In a mouse model of the genetic disease cystic fibrosis, we previously showed that in vivo administration of lubiprostone resulted in greater mucus accumulation in the small intestine. The aim of this study was to directly test whether lubiprostone stimulates intestinal mucin release. Mucin release was measured by mounting segments (4-5 cm) of mouse proximal-mid small intestine in an organ bath, allowing access to the perfusate (luminal) and the bath (serosal) solutions. Nifedipine (10-6 M) and indomethacin (10-5 M) were included in all solutions to inhibit smooth muscle activity and endogenous prostaglandin production, respectively. The tissue was equilibrated under flow for 30 min, using the perfusate collected during the final 10 min of the equilibration period to measure unstimulated release rate. Stimulus was then added to either the perfusate or the bath and the perfusate was collected for another 30 min to measure the stimulated mucin release rate. Mucin in perfusates was quantified by periodic acid-Schiff's base dot-blot assay, using purified pig gastric mucin as a standard. When applied luminally at 1 μM lubiprostone was ineffective at stimulating mucin release. When added to the serosal solution, 1 μM lubiprostone stimulated mucin release to ~300% of the unstimulated rate. As a positive control, serosal 1 μM prostaglandin E2 increased mucin release to ~400% of the unstimulated rate. These results support the idea that lubiprostone has prostaglandin-like actions on the intestine, which includes stimulation of mucin release. Stimulation of mucin release by lubiprostone may be protective in gastrointestinal conditions where loss of mucus is believed to contribute to pathogenesis. Thus, in addition to chronic constipation, there is greater potential for the therapeutic applications of lubiprostone.

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.

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 +/- 28 x 10(3) IE, p < 0.05, two-tailed paired t-test). No difference in in vitro islet viability was observed between the two groups following glucose perifusion with the calculated stimulation index of 4.6 +/- 0.6 for the perfusion group and 4.2 +/- 0.7 for the syringe-loaded group. Controlled perfusion via the pancreatic duct allows the effective delivery of the enzyme achieving maximal distension to all regions of the pancreas leading to an increased recovery of the islets with no detrimental effect on subsequent in vitro islet function.

Continuous Real-time Viability Assessment of Kidneys Based on Oxygen Consumption

PubMed Central

Weegman, B.P.; Kirchner, V.A.; Scott, W.E.; Avgoustiniatos, E.S.; Suszynski, T.M.; Ferrer-Fabrega, J.; Rizzari, M.D.; Kidder, L.S.; Kandaswamy, R.; Sutherland, D.E.R.; Papas, K.K.

2010-01-01

Background Current ex vivo quality assessment of donor kidneys is limited to vascular resistance measurements and histological analysis. New techniques for the assessment of organ quality before transplantation may further improve clinical outcomes while expanding the depleted deceased-donor pool. We propose the measurement of whole organ oxygen consumption rate (WOOCR) as a method to assess the quality of kidneys in real time before transplantation. Methods Five porcine kidneys were procured using a donation after cardiac death (DCD) model. The renal artery and renal vein were cannulated and the kidney connected to a custom-made hypothermic machine perfusion (HMP) system equipped with an inline oxygenator and fiber-optic oxygen sensors. Kidneys were perfused at 8°C, and the perfusion parameters and partial oxygen pressures (pO2) were measured to calculate WOOCR. Results Without an inline oxygenator, the pO2 of the perfusion solution at the arterial inlet and venous outlet diminished to near 0 within minutes. However, once adequate oxygenation was provided, a significant pO2 difference was observed and used to calculate the WOOCR. The WOOCR was consistently measured from presumably healthy kidneys, and results suggest that it can be used to differentiate between healthy and purposely damaged organs. Conclusions Custom-made HMP systems equipped with an oxygenator and inline oxygen sensors can be applied for WOOCR measurements. We suggest that WOOCR is a promising approach for the real-time quality assessment of kidneys and other organs during preservation before transplantation. PMID:20692397

Effects of anions and cations on the resting membrane potential of internally perfused barnacle muscle fibres

PubMed Central

Lakshminarayanaiah, N.; Rojas, E.

1973-01-01

1. Single barnacle muscle fibres from Megabalanus psittacus (Darwin) were internally perfused with a number of K salt solutions (200 mM) which were made isotonic to the barnacle saline with sucrose. 2. 200 mM-K acetate solution, in general, was found to be more effective than other solutions of K salts in generating and maintaining stable resting membrane potential of -56·0 ± 0·7 mV (all potentials are referred to the external solutions as ground). The various K salts, on the basis of the magnitude of the resting potential they generated in the muscle fibres, followed the sequence, acetate > isethionate > aspartate > glutamate > fluoride > monohydrogen phosphate > succinate > citrate > sulphate > oxalate > iodobenzoate > ferrocyanide > chlorate > nitrate > chloride > thiocyanate > iodide > bromide > cyanide. 3. The resting potential in muscle fibres perfused with solutions of acetate, aspartate and glutamate increased linearly with the logarithm of the K concentration (slope = 30·4 mV for K acetate and 27·4 for K aspartate and glutamate) when the ionic strength of the solutions was progressively increased from 50 to 650 mM. On the other hand, similar increase of ionic strength beyond 200 mM of solutions of K isethionate, fluoride, monohydrogen phosphate, succinate and citrate depolarized the muscle fibres. 4. Perfusion of acetate solutions of other alkali metal ions gave low values for the resting potential and followed the sequence K > Na > Rb > Li > Cs. Also NH4 and Tris ions gave low values for the resting potential which underwent oscillations associated with the twitching of the fibre and occasionally became positive in value (action potential). 5. Addition of tetraethyl ammonium chloride (TEA-Cl), 20-100 mM, to K acetate solutions (200 mM) depolarized the fibre membrane and the consequent reduction of resting potential varied linearly with the logarithm of TEA concentration. 6. Replacement of chloride ion by acetate or isethionate in the external solution did not change significantly the resting potential although the values were consistently lower by about 2 mV. 7. Complete elimination of K in the external solution and reduction of its ionic strength using sucrose depolarized the muscle fibres by about 27 mV when Na was changed from 475 to 1 mM. Under these conditions, external solutions completely in acetate form gave resting potentials which were more positive than those observed in completely chloride solutions by 6-8 mV. 8. Replacement of Na by Li, Tris, choline, tetramethyl or tetraethyl ammonium ion in the external solution made the values of the resting potential more positive (depolarization). Similarly increasing the concentration of K (or Cs or Rb in place of K) by correspondingly decreasing the concentration of Na in the outside solution depolarized the fibres and the resting potential became zero at a concentration of 280 mM (or 308 or 1500 mM for Rb or Cs, respectively) on extrapolation. PMID:4754874

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2018-05-01

This study sought to compare the diagnostic accuracy of visual and quantitative analyses of myocardial perfusion cardiovascular magnetic resonance against a reference standard of quantitative coronary angiography. Visual analysis of perfusion cardiovascular magnetic resonance studies for assessing myocardial perfusion has been shown to have high diagnostic accuracy for coronary artery disease. However, only a few small studies have assessed the diagnostic accuracy of quantitative myocardial perfusion. This retrospective study included 128 patients randomly selected from the CE-MARC (Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease) study population such that the distribution of risk factors and disease status was proportionate to the full population. Visual analysis results of cardiovascular magnetic resonance perfusion images, by consensus of 2 expert readers, were taken from the original study reports. Quantitative myocardial blood flow estimates were obtained using Fermi-constrained deconvolution. The reference standard for myocardial ischemia was a quantitative coronary x-ray angiogram stenosis severity of ≥70% diameter in any coronary artery of >2 mm diameter, or ≥50% in the left main stem. Diagnostic performance was calculated using receiver-operating characteristic curve analysis. The area under the curve for visual analysis was 0.88 (95% confidence interval: 0.81 to 0.95) with a sensitivity of 81.0% (95% confidence interval: 69.1% to 92.8%) and specificity of 86.0% (95% confidence interval: 78.7% to 93.4%). For quantitative stress myocardial blood flow the area under the curve was 0.89 (95% confidence interval: 0.83 to 0.96) with a sensitivity of 87.5% (95% confidence interval: 77.3% to 97.7%) and specificity of 84.5% (95% confidence interval: 76.8% to 92.3%). There was no statistically significant difference between the diagnostic performance of quantitative and visual analyses (p = 0.72). Incorporating rest myocardial blood flow values to generate a myocardial perfusion reserve did not significantly increase the quantitative analysis area under the curve (p = 0.79). Quantitative perfusion has a high diagnostic accuracy for detecting coronary artery disease but is not superior to visual analysis. The incorporation of rest perfusion imaging does not improve diagnostic accuracy in quantitative perfusion analysis. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

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

DTIC Science & Technology

2001-10-25

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

Further studies on the role of prostaglandin in fever

PubMed Central

Dey, P. K.; Feldberg, W.; Gupta, K. P.; Milton, A. S.; Wendlandt, Sabine

1974-01-01

1. Experiments were carried out in unanaesthetized cats to find out if a prostaglandin is the mediator (a) for the long lasting fever which often follows injections of phsyiological salt solutions into the cerebral ventricles or into the cisterna magna, as well as their perfusions through the cerebral ventricles, and (b) for the sodium fever which occurs during a perfusion of the cerebral ventricles with calcium-free artificial c.s.f. A fever mediated by prostaglandin should be accompanied by an increase of prostaglandin activity in cisternal c.s.f., and be abolished or prevented by antipyretics like paracetamol or indomethacin which inhibit prostaglandin synthesis. Both criteria were applied. 2. The fever which follows injections or perfusions of physiological salt solutions appears to be mediated by a prostaglandin of the E series, probably E2 (PGE2) because it was accompanied by increased prostaglandin E-like activity in the c.s.f. and abolished by paracetamol and indomethacin. During the first few days after pre-treatment of the cats with intramuscular chloramphenicol the injections were rarely followed by fever. 3. The fever which occurs during a perfusion with calcium-free artificial c.s.f. appears not to be mediated by prostaglandin, because it was not associated with increased prostaglandin activity in the cisternal effluent, and not prevented by paracetamol or indomethacin, although these antipyretics usually attenuated the fever. 4. A perfusion of the cerebral ventricles with artificial c.s.f. containing calcium in an abnormally high concentration (6·25 mM) brought down fever produced by PGE1, or PGE2, or bacterial pyrogen. PMID:4215879

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.

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.

Specificity of neutral amino acid uptake at the basolateral side of the epithelium in the cat salivary gland in situ.

PubMed

Bustamante, J C; Mann, G E; Yudilevich, D L

1981-01-01

1. Amino acid uptake was measured in resting cat submandibular glands with either a natural blood supply or perfused at constant flow with a Krebs-albumin solution. Following a bolus arterial injection of a 3H-labelled amino acid and D-[14C]mannitol (extracellular reference tracer), the venous effluent was immediately sampled sequentially. The maximal uptake, Umax, from the blood or perfusate was determined from the paired-tracer dilution curves using the expression: uptake % = (1 -- (3H/14C) X 100). 2. In glands with a natural blood supply, Umax values up to 46% were measured for short-chain (serine and alanine) and long-chain (valine, methionine, leucine, isoleucine, 1-amino-cyclopentane cyclopentane carboxylic acid, phenylalanine, tryptophan, tyrosine, histidine and glutamine) neutral amino acids. In contrast, Umax was negligible for amino acids of the imino-glycine group (proline and glycine) and the nonmetabolized amino acids, 2-aminoisobutyric acid (AIB) and methylaminoisobutyric acid (MeAIB). 3. In glands with a natural blood supply addition of an unlabelled amino acid to the tracer injectate reduced Umax for the test acid by up to 80%. The pattern of these interactions suggested the presence of two transport systems for neutral amino acids, one preferring short-chain and the other long-chain amino acids. 4. In glands perfused at constant flow rates with an amino acid-free Krebs-albumin solution high Umax values were measured: L-serine (66%), L-alanine (54%), L-leucine (43%), L-phenylalanine (42%) and L-tyrosine (51%). Only a low uptake was observed for L-proline (8%) and glycine (14%). There was no uptake of methylaminoisobutyric acid which confirms the result obtained in glands with an intact circulation. 5. Saturation of L-phenylalanine influx was observed in perfused glands as the perfusate concentration of unlabelled L-phenylalanine was increased from 0.5 to 20 mmol . 1-1. A Michaelis--Menten analysis based on a single entry system indicated an apparent Km of 6.4 +/- 0.8 mmol . 1-1 and a Vmax of 1719 +/- 94 nmol . min-1g.-1 6. Since the fenestrated capillaries in the salivary gland are readily permeable to the test amino acid and D-mannitol, it is most probable that the amino acid carriers are located in the basolateral side of the epithelium. 7. The use of a paired-tracer dilution technique to measure uptake in a single circulatory passage has enabled a detailed characterization of neutral amino acid transport in the salivary gland and has overcome the limitation of previous studies based on solute transfer from blood to saliva.

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

DTIC Science & Technology

2014-07-01

solution. Tissue processing and histological procedures Tissues were excised, weighed, embedded in a talcum- based gel, and flash frozen in 2...the overall level of perfusion was low and was not distributed evenly throughout the defect. GFP MVF transplantation MVFs derived from GFP...support vasculogenesis. However, the levels of VEGF secreted by MVFs were significantly lower than that of ASCs under both normoxic and hypoxic

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.

Acidification of the gill cells of the shore crab Carcinus mediterraneus: Its physiological significance

NASA Astrophysics Data System (ADS)

Lucu, Č.; Siebers, D.

1995-03-01

In a preparation of isolated gills of the shore crab Carcinus mediterraneus perfused with dilute sea water (pH 8.1, 200 mM Na+) which was identical to the bathing solution of the gill, acidification of the collected perfusate was observed. Acidification was not affected by 10-4 M EIPA (5-[N-ethyl-N-isopropyl]amiloride), a strong inhibitor of Na+/H+ exchange. However, in the presence of 10-4 M acetazolamide, acidification was greatly blocked. The significant decrease of the acid load of the perfusate is considered to be a result of inhibition of the branchial intracellular carbonic anhydrase catalyzing the formation of H+ ions.

A comparative analysis of the dependences of the hemodynamic parameters on changes in ROI's position in perfusion CT scans

NASA Astrophysics Data System (ADS)

Choi, Yong-Seok; Cho, Jae-Hwan; Namgung, Jang-Sun; Kim, Hyo-Jin; Yoon, Dae-Young; Lee, Han-Joo

2013-05-01

This study performed a comparative analysis of cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), and mean time-to-peak (TTP) obtained by changing the region of interest's (ROI) anatomical positions, during CT brain perfusion. We acquired axial source images of perfusion CT from 20 patients undergoing CT perfusion exams due to brain trauma. Subsequently, the CBV, CBF, MTT, and TTP values were calculated through data-processing of the perfusion CT images. The color scales for the CBV, CBF, MTT, and TTP maps were obtained using the image data. Anterior cerebral artery (ACA) was taken as the standard ROI for the calculations of the perfusion values. Differences in the hemodynamic average values were compared in a quantitative analysis by placing ROI and the dividing axial images into proximal, middle, and distal segments anatomically. By performing the qualitative analysis using a blind test, we observed changes in the sensory characteristics by using the color scales of the CBV, CBF, and MTT maps in the proximal, middle, and distal segments. According to the qualitative analysis, no differences were found in CBV, CBF, MTT, and TTP values of the proximal, middle, and distal segments and no changes were detected in the color scales of the the CBV, CBF, MTT, and TTP maps in the proximal, middle, and distal segments. We anticipate that the results of the study will useful in assessing brain trauma patients using by perfusion imaging.

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

The role of Rho-kinase and calcium ions in constriction triggered by ET-1.

PubMed

Wiciński, Michał; Szadujkis-Szadurska, Katarzyna; Węclewicz, Mateusz M; Malinowski, Bartosz; Matusiak, Grzegorz; Walczak, Maciej; Wódkiewicz, Eryk; Grześk, Grzegorz; Pawlak-Osińska, Katarzyna

2018-05-05

Endothelin-1 (ET-1) is one of the key factors regulating tension of smooth muscles in blood vessels. It is believed that ET-1 plays an important role in pathogenesis of hypertension, and cardiovascular diseases; therefore, research in order to limit ET-1-mediated action is still in progress. The main objective of this paper was to evaluate the role of Rho-kinase in the ET-1-induced constriction of arteries. The analysis also included significance of intra- and extracellular pool of calcium ions in constriction triggered by ET-1. The studies were performed on perfused Wistar rat tail arteries. Concentration response curve (CRC) was determined for ET-1 in the presence of increased concentrations of Rho-kinase inhibitor (Y-27632) and IP3-receptor antagonist (2APB), both in reference to constriction triggered by solely ET-1. Afterwards, the influence of calcium ions present in the perfusion fluid was evaluated in terms of the effect triggered by 2APB and occurring in arteries constricted by ET-1. ET-1, in concentration dependent manner, leads to increase in perfusion pressure. Y-27632 and 2APB lead to shift of the concentration response curve for ET-1 to the right with simultaneously lowered maximum effect. There was no difference in reaction of the artery constricted by ET-1 and treated with 2APB in solution containing calcium and in calcium-free solution. Vasoconstrictive action of endothelin is not significantly dependent on the inflow of extracellular calcium, but it is proportional to inflow of Ca 2+ related to activation of IP3 receptors and to Rho-kinase activity. Copyright © 2018. Published by Elsevier Inc.

Proximal bicarbonate absorption independent of Na+-H+ exchange: effect of bicarbonate load.

PubMed

Bank, N; Aynedjian, H S; Mutz, B F

1989-04-01

To study proximal tubule bicarbonate absorption that is not due to the neutral Na+-H+ antiporter, mid to late proximal convolutions of the rat kidney were microperfused in vivo with a sodium-free choline solution containing 10(-3) M amiloride. The average sodium concentration resulting from sodium influx was 12 mM. At such low intraluminal [Na+], 10(-3) M amiloride should have inhibited the Na+-H+ antiporter by greater than 95%. When 25 mM HCO3- was in the perfusion fluid, measured total CO2 absorption was 100 pmol.mm-1.min-1. When luminal [HCO3-] was raised to 50 mM, and blood [HCO3-] was also raised to approximately 50 mM to avoid a transepithelial HCO3- concentration gradient, total CO2 absorption increased to greater than 300 pmol.mm-1.min-1. Thus raising intraluminal HCO3- concentration caused a marked increase in total CO2 absorption even though intraluminal [Na+] was low and amiloride was present. Control perfusions containing 140 mM Na+ yielded total CO2 absorption that was approximately 100 pmol.mm-1.min-1 higher than with the respective sodium-free perfusion solutions. In additional experiments, either DCCD or NEM was added to sodium-free perfusion solutions to inhibit H+-ATPase. These inhibitors reduced Na+-H+ independent total CO2 absorption markedly. Our observations suggest that under physiological acid-base conditions, sodium-independent H+ secretion can account for approximately 50% of total HCO3- absorption in mid to late proximal convolutions. This mechanism is stimulated by an increase in ambient HCO(-3) concentration to a degree that might account for the load-dependency of proximal HCO(-3) absorption in these segments of the proximal tubule.(ABSTRACT TRUNCATED AT 250 WORDS)

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

Comprehensive Assessment of Coronary Artery Disease by Using First-Pass Analysis Dynamic CT Perfusion: Validation in a Swine Model.

PubMed

Hubbard, Logan; Lipinski, Jerry; Ziemer, Benjamin; Malkasian, Shant; Sadeghi, Bahman; Javan, Hanna; Groves, Elliott M; Dertli, Brian; Molloi, Sabee

2018-01-01

Purpose To retrospectively validate a first-pass analysis (FPA) technique that combines computed tomographic (CT) angiography and dynamic CT perfusion measurement into one low-dose examination. Materials and Methods The study was approved by the animal care committee. The FPA technique was retrospectively validated in six swine (mean weight, 37.3 kg ± 7.5 [standard deviation]) between April 2015 and October 2016. Four to five intermediate-severity stenoses were generated in the left anterior descending artery (LAD), and 20 contrast material-enhanced volume scans were acquired per stenosis. All volume scans were used for maximum slope model (MSM) perfusion measurement, but only two volume scans were used for FPA perfusion measurement. Perfusion measurements in the LAD, left circumflex artery (LCx), right coronary artery, and all three coronary arteries combined were compared with microsphere perfusion measurements by using regression, root-mean-square error, root-mean-square deviation, Lin concordance correlation, and diagnostic outcomes analysis. The CT dose index and size-specific dose estimate per two-volume FPA perfusion measurement were also determined. Results FPA and MSM perfusion measurements (P FPA and P MSM ) in all three coronary arteries combined were related to reference standard microsphere perfusion measurements (P MICRO ), as follows: P FPA_COMBINED = 1.02 P MICRO_COMBINED + 0.11 (r = 0.96) and P MSM_COMBINED = 0.28 P MICRO_COMBINED + 0.23 (r = 0.89). The CT dose index and size-specific dose estimate per two-volume FPA perfusion measurement were 10.8 and 17.8 mGy, respectively. Conclusion The FPA technique was retrospectively validated in a swine model and has the potential to be used for accurate, low-dose vessel-specific morphologic and physiologic assessment of coronary artery disease. © RSNA, 2017.

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

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

Hubbard, L; Ziemer, B; Sadeghi, B

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

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

PubMed

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

2013-05-01

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

Static inflation attenuates ischemia/reperfusion injury in an isolated rat lung in situ.

PubMed

Kao, Shang Jyh; Wang, David; Yeh, Diana Yu-Wung; Hsu, Kang; Hsu, Yung Hsiang; Chen, Hsing I

2004-08-01

Ischemia (I)/reperfusion (R) lung injury is an important clinical issue in lung transplantation. In the present study, we observed the effects of lung static inflation, different perfusates, and ventilatory gas with nitrogen or oxygen on the I/R-induced pulmonary damage. A total of 96 male Sprague-Dawley rats were used. The lung was isolated in situ. In an isolated lung, the capillary filtration coefficient (Kfc), lung weight gain (LWG), lung weight (LW)/body weight (BW) ratio, and protein concentration in BAL fluid (PCBAL) were measured or calculated to evaluate the degree of lung injury. Histologic examinations with hematoxylin-eosin staining were performed. I/R caused lung injury, as reflected by increases in Kfc, LWG, LW/BW, and PCBAL. The histopathologic picture revealed the presence of hyaline membrane formation and the infiltration of inflammatory cells. These values were significantly attenuated by static lung inflation. The I/R lung damage appeared to be less in the lung perfused with whole blood than in the lung perfused with an isotonic solution. Therapy with ventilatory air (ie, nitrogen or oxygen) did not alter the I/R lung damage. The data suggest that lung inflation is protective to I/R injury, irrespective of the type of ventilatory air used for treatment. The preservation of the lung for transplantation is better kept at a static inflation state and perfused with whole blood instead of an isotonic physiologic solution.

Spinal decompression sickness: mechanical studies and a model.

PubMed

Hills, B A; James, P B

1982-09-01

Six experimental investigations of various mechanical aspects of the spinal cord are described relevant to its injury by gas deposited from solution by decompression. These show appreciable resistances to gas pockets dissipating by tracking along tissue boundaries or distending tissue, the back pressure often exceeding the probable blood perfusion pressure--particularly in the watershed zones. This leads to a simple mechanical model of spinal decompression sickness based on the vascular "waterfall" that is consistent with the pathology, the major quantitative aspects, and the symptomatology--especially the reversibility with recompression that is so difficult to explain by an embolic mechanism. The hypothesis is that autochthonous gas separating from solution in the spinal cord can reach sufficient local pressure to exceed the perfusion pressure and thus occlude blood flow.

[The role of delta-1 opiate receptors in regulation of contractility in isolated rat heart during normal oxygenation and ischemia-reperfusion].

PubMed

Lasukova, T V; Maslov, L N; Lishmanov, Iu B; Gross, G J

2004-01-01

The experiments on isolated rat heart demonstrated significant decrease in reperfusion-induced damage of cardiomyocytes by addition of selective delta 1 receptor agonist DPDPE (0.1 mg/l) to the perfusion solution. On the contrary, no cardioprotective effect was observed for 0.5 mg/l concentration of the peptide or after its intravenous injection. Stimulation of the cardiac delta 1 opioid receptors by intravenous injection of 0.5 mg/kg DPDPE or its addition to the perfusion solution decreased myocardial contractility both in conditions of normal oxygenation and during reperfusion. Thus, the cardioprotective and negative inotropic effect of DPDPE is mediated by activation of the cardiac delta 1 opioid receptors.

Cutaneous interstitial nitric oxide concentration does not increase during heat stress in humans

NASA Technical Reports Server (NTRS)

Crandall, C. G.; MacLean, D. A.

2001-01-01

Inhibition of cutaneous nitric oxide (NO) synthase reduces the magnitude of cutaneous vasodilation during whole body heating in humans. However, this observation is insufficient to conclude that NO concentration increases in the skin during a heat stress. This study was designed to test the hypothesis that whole body heating increases cutaneous interstitial NO concentration. This was accomplished by placing 2 microdialysis membranes in the forearm dermal space of 12 subjects. Both membranes were perfused with lactated Ringer solutions at a rate of 2 microl/min. In both normothermia and during whole body heating via a water perfused suit, dialysate from these membranes were obtained and analyzed for NO using the chemiluminescence technique. In six of these subjects, after the heat stress, the membranes were perfused with a 1 M solution of acetylcholine to stimulate NO release. Dialysate from these trials was also assayed to quantify cutaneous interstitial NO concentration. Whole body heating increased skin temperature from 34.6 +/- 0.2 to 38.8 +/- 0.2 degrees C (P < 0.05), which increased sublingual temperature (36.4 +/- 0.1 to 37.6 +/- 0.1 degrees C; P < 0.05), heart rate (63 +/- 5 to 93 +/- 5 beats/min; P < 0.05), and skin blood flow over the membranes (21 +/- 4 to 88 +/- 10 perfusion units; P < 0.05). NO concentration in the dialysate did not increase significantly during of the heat stress (7.6 +/- 0.7 to 8.6 +/- 0.8 microM; P > 0.05). After the heat stress, administration of acetylcholine in the perfusate significantly increased skin blood flow (128 +/- 6 perfusion units) relative to both normothermic and heat stress values and significantly increased NO concentration in the dialysate (15.8 +/- 2.4 microM). These data suggest that whole body heating does not increase cutaneous interstitial NO concentration in forearm skin. Rather, NO may serve in a permissive role in facilitating the effects of an unknown neurotransmitter, leading to cutaneous vasodilation during a heat stress.

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.

[Determination of H2S in Rat Intestinal Perfusion Solution Based on Fluorescence Analysis].

PubMed

Hou, Jun-feng; Li, Xin-xia; Shen, Xue-ru; Huojia, Miliban; Guan, Ming

2015-08-01

Under alkaline conditions, Fluorescein mercury has strong fluorescence, however, when it met S(2-), its fluorescence would quench, in view of the above, a fluorescence method for determination of H2S in biological samples was established. In the 0.1 mol · L(-1) NaOH dilution, when the concentration of fluorescein Mercury and Na2S was 5.0 × 10(-5) and 1.0 × 10(-5) mol · L(-1) respectively, the fluorescence intensity of system was determined at 522 nm. The results showed that, at the range of 4.0 × 10(-7)~2.0 × 10(-6) mol · L(-1), the concentration decreasing of H2S and fluorescence intensity had good linear relationship, r=0.9980, the RSD of precision test was 4.59% (n=7), the detection limit was 3.5 × 10(-8) mol · L(-1), the content of H2S in the sample were 1.01 × 10(-6) and 1.15 × 10(-6) mol · L(-1), and the recovery rate was 95.8%~101.0%, the method has the advantages of simple operation, high sensitivity, good selectivity, can accurately determine of H2S in intestinal perfused solution, and provides the basis for the determination of endogenous H2S.

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.

Bicarbonate absorption stimulates active calcium absorption in the rat proximal tubule.

PubMed Central

Bomsztyk, K; Calalb, M B

1988-01-01

To evaluate the effect of luminal bicarbonate on calcium reabsorption, rat proximal tubules were perfused in vivo. Perfusion solution contained mannitol to reduce water flux to zero. Total Ca concentration was measured by atomic absorption spectrometry, Ca ion concentration in the tubule lumen (CaL2+) and the peritubular capillary (CaP2+), and luminal pH (pHL) with ion-selective microelectrodes and transepithelial voltage (VTE) with conventional microelectrodes. When tubules were perfused with buffer-free Cl-containing solution, net Ca absorption (JCa) averaged 3.33 pmol/min. Even though VTE was 1.64 mV lumen-positive, CaL2+, 1.05 mM, did not fall below the concentration in the capillary blood, 1.07 mM. When 27 mM of Cl was replaced with HCO3, there was luminal fluid acidification. Despite a decrease in VTE and CaL2+, JCa increased to 7.13 pmol/min, indicating that the enhanced JCa could not be accounted for by the reduced electrochemical gradient, delta CCa. When acetazolamide or an analogue of amiloride was added to the HCO3 solution, JCa was not different from the buffer-free solution, suggesting that HCO3-stimulated JCa may be linked to acidification. To further test this hypothesis, we used 27 mM Hepes as the luminal buffer. With Hepes there was luminal fluid acidification and JCa was not different from the buffer-free solution but delta CCa was significantly reduced, indicating enhanced active calcium transport. We conclude from the results of the present study that HCO3 stimulates active Ca absorption, a process that may be linked to acidification-mediated HCO3 absorption. PMID:3366902

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

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

PubMed

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

2016-10-01

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

Role of glycolysis in maintenance of the action potential duration and contractile activity in isolated perfused rat heart.

PubMed

Opie, L H; Tuschmidt, R; Bricknell, O; Girardier, L

1980-01-01

1. Changing substrates from glucose to pyruvate in paced isolated rat hearts, perfused by the Langendorff technique at 65 cm H2O with a Krebs-Henseleit bicarbonate buffer, produced effects which are opposite to those of ouabain treatment: negative inotropy, decreased work efficiency, hyperpolarization, increased maximum rate of rise and amplitude of the action potential, increased conduction velocity. 2. All the effects resulting from perfusion with pyruvate can be reversed by adding ouabain at a concentration of 100 microM. 3. The correlation between various tissue metabolises and change in contractile force (delta F), rate of tension development [maximum + (dF/dt)] and rate of relaxation [maximum -(dF/dt)] was studied by multiple linear regression. No significant correlation was found with either glycogen content and tissue lactate or with cAMP and cGMP. A weak negative correlation was found with ATP and phosphocreatine. The strongest correlation was found 76 to 807 nM/g in passing from glucose- to pyruvate-containing perfusion solution. 4. In vitro tests performed with a solution containing high energy phosphates and magnesium at concentrations equal to their calculated values in the cytosol (pH 7.0) showed that a significant negative correlation exists between citrate concentration (range: 1 and 1500 M) and free calcium concentration in the micromole range. 5. It is concluded that the effects of pyruvate (non glucose substrate) perfusion could be mediated by a decrease in cytosolic-free calcium resulting from an increase in intracellular citrate. The observation that all these effects can be reversed by ouabain is taken as a circumstantial evidence of a common mechanism.

Dipeptide transport and hydrolysis in isolated loops of rat small intestine: effects of stereospecificity.

PubMed Central

Lister, N; Sykes, A P; Bailey, P D; Boyd, C A; Bronk, J R

1995-01-01

1. Isolated jejunal loops of rat small intestine were perfused by a single pass of bicarbonate Krebs-Ringer solution containing either D- or L-phenylalanine or one of eight dipeptides formed from D- or L-alanine plus D- or L-phenylalanine. 2. At 0.5 mM L-phenylalanyl-L-alanine increased serosal phenylalanine appearance to forty times the control rate giving a value similar to that found with 0.5 mM free L-phenylalanine. No serosal dipeptide could be detected. 3. Perfusions with the two mixed dipeptides with N-terminal D-amino acids (D-alanyl-L-phenylalanine and D-phenylalanyl-L-alanine) gave rise to the appearance of intact dipeptides in the serosal secretions although there were substantial differences in their rates of absorption and subsequent hydrolysis. 4. L-Alanyl-D-phenylalanine was absorbed from the lumen three to five times as fast as L-phenylalanyl-D-alanine. At 1 mM L-alanyl-D-phenylalanine transferred D-phenylalanine across the epithelial layer at more than seven times the rate found with the same concentration of the free D-amino acid. 5. Perfusions with D-alanyl-D-phenylalanine or D-phenylalanyl-D-alanine showed that these two dipeptides are poor substrates for both transport and hydrolysis by the rat small intestine. 6. Analysis of mucosal tissue extracts after perfusion with the two mixed dipeptides with N-terminal D-amino acids revealed that both dipeptides were accumulated within the mucosa and suggested that exit across the basolateral membrane was rate limiting for transepithelial dipeptide transport. Images Figure 5 PMID:7602518

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.

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.

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

NASA Astrophysics Data System (ADS)

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

2011-03-01

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

Histogram based analysis of lung perfusion of children after congenital diaphragmatic hernia repair.

PubMed

Kassner, Nora; Weis, Meike; Zahn, Katrin; Schaible, Thomas; Schoenberg, Stefan O; Schad, Lothar R; Zöllner, Frank G

2018-05-01

To investigate a histogram based approach to characterize the distribution of perfusion in the whole left and right lung by descriptive statistics and to show how histograms could be used to visually explore perfusion defects in two year old children after Congenital Diaphragmatic Hernia (CDH) repair. 28 children (age of 24.2±1.7months; all left sided hernia; 9 after extracorporeal membrane oxygenation therapy) underwent quantitative DCE-MRI of the lung. Segmentations of left and right lung were manually drawn to mask the calculated pulmonary blood flow maps and then to derive histograms for each lung side. Individual and group wise analysis of histograms of left and right lung was performed. Ipsilateral and contralateral lung show significant difference in shape and descriptive statistics derived from the histogram (Wilcoxon signed-rank test, p<0.05) on group wise and individual level. Subgroup analysis (patients with vs without ECMO therapy) showed no significant differences using histogram derived parameters. Histogram analysis can be a valuable tool to characterize and visualize whole lung perfusion of children after CDH repair. It allows for several possibilities to analyze the data, either describing the perfusion differences between the right and left lung but also to explore and visualize localized perfusion patterns in the 3D lung volume. Subgroup analysis will be possible given sufficient sample sizes. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

The effectiveness and cost-effectiveness of methods of storing donated kidneys from deceased donors: a systematic review and economic model.

PubMed

Bond, M; Pitt, M; Akoh, J; Moxham, T; Hoyle, M; Anderson, R

2009-08-01

To review the evidence for the effectiveness and cost-effectiveness of storing kidneys from deceased donors prior to transplantation, using cold static storage solutions or pulsatile hypothermic machine perfusion. Electronic databases were searched in January 2008 and updated in May 2008 for systematic reviews and/or meta-analyses, randomised controlled trials (RCTs), other study designs and ongoing research. Sources included: Cochrane Library, MEDLINE, EMBASE, CINAHL, ISI Web of Knowledge, DARE, NRR, ReFeR, Current Controlled Trials, and (NHS) HTA. Bibliographies of articles were searched for further relevant studies, and the Food and Drugs Administration (FDA) and European Regulatory Agency Medical Device Safety Service websites were searched. Only English language papers were sought. The perfusion machines identified were the LifePort Kidney Transporter (Organ Recovery Systems) and the RM3 Renal Preservation System (Waters Medical Systems). The cold storage solutions reviewed were: University of Wisconsin, ViaSpan; Marshall's hypertonic citrate, Soltran; and Genzyme, Celsior. Each intervention was compared with the others as data permitted. The population was recipients of kidneys from deceased donors. The main outcomes were measures of graft survival, patient survival, delayed graft function (DGF), primary non-function (PNF), discard rates of non-viable kidneys, health-related quality of life and cost-effectiveness. Where data permitted the results of studies were pooled using meta-analysis. A Markov (state transition) model was developed to simulate the main post-transplantation outcomes of kidney graft recipients. Eleven studies were included: three full journal published RCTs, two ongoing RCTs [European Machine Preservation Trial (MPT) and UK Pulsatile Perfusion in Asystolic donor Renal Transplantation (PPART) study], one cohort study, three full journal published retrospective record reviews and two retrospective record reviews published as posters or abstracts only. For LifePort versus ViaSpan, no significant differences were found for DGF, PNF, acute rejection, duration of DGF, creatinine clearance or toxicity, patient survival or graft survival at 6 months, but graft survival was better at 12 months post transplant with machine perfusion (LifePort = 98%, ViaSpan = 94%, p < 0.03). For LifePort versus RM3, all outcomes favoured RM3, although the results may be unreliable. For ViaSpan versus Soltran, there were no significant differences in graft survival for cold ischaemic times up to 36 hours. For ViaSpan versus Celsior, no significant differences were found on any outcome measure. In terms of cost-effectiveness, data from the MPT suggested that machine preservation was cheaper and generated more quality-adjusted life-years (QALYs), while the PPART study data suggested that cold storage was preferable on both counts. The less reliable deterministic outputs of the cohort study suggested that LifePort would be cheaper and would generate more QALYs than Soltran. Sensitivity analyses found that changes to the differential kidney storage costs between comparators have a very low impact on overall net benefit estimates; where differences in effectiveness exist, dialysis costs are important in determining overall net benefit; DGF levels become important only when differences in graft survival are apparent between patients experiencing immediate graft function (IGF) versus DGF; relative impact of differential changes to graft survival for patients experiencing IGF as opposed to DGF depends on the relative proportion of patients experiencing each of these two outcomes. The conclusions drawn for the comparison of machine perfusion with cold storage depend on which trial data are used in the model. Owing to the lack of good research evidence that either ViaSpan or Soltran is better than the other, the cheaper, Soltran, may be preferable. In the absence of a cost-utility analysis, the results of our meta-analysis of the RCTs comparing ViaSpan with Celsior indicate that these cold storage solutions are equivalent. Further RCTs of comparators of interest to allow for appropriate analysis of subgroups and to determine whether either of the two machines under consideration produces better outcomes may be useful. In addition, research is required to: establish the strength and reliability of the presumed causal association between DGF and graft, and patient survival; investigate the utility impacts of renal replacement therapy; determine what the additional cost, survival and QALY impacts are of decreased or increased non-viable kidneys when discarded pre transplantation; and identify a reliable measure for predicting kidney viability from machine perfusion.

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.

Impact of CT perfusion imaging on the assessment of peripheral chronic pulmonary thromboembolism: clinical experience in 62 patients.

PubMed

Le Faivre, Julien; Duhamel, Alain; Khung, Suonita; Faivre, Jean-Baptiste; Lamblin, Nicolas; Remy, Jacques; Remy-Jardin, Martine

2016-11-01

To evaluate the impact of CT perfusion imaging on the detection of peripheral chronic pulmonary embolisms (CPE). 62 patients underwent a dual-energy chest CT angiographic examination with (a) reconstruction of diagnostic and perfusion images; (b) enabling depiction of vascular features of peripheral CPE on diagnostic images and perfusion defects (20 segments/patient; total: 1240 segments examined). The interpretation of diagnostic images was of two types: (a) standard (i.e., based on cross-sectional images alone) or (b) detailed (i.e., based on cross-sectional images and MIPs). The segment-based analysis showed (a) 1179 segments analyzable on both imaging modalities and 61 segments rated as nonanalyzable on perfusion images; (b) the percentage of diseased segments was increased by 7.2 % when perfusion imaging was compared to the detailed reading of diagnostic images, and by 26.6 % when compared to the standard reading of images. At a patient level, the extent of peripheral CPE was higher on perfusion imaging, with a greater impact when compared to the standard reading of diagnostic images (number of patients with a greater number of diseased segments: n = 45; 72.6 % of the study population). Perfusion imaging allows recognition of a greater extent of peripheral CPE compared to diagnostic imaging. • Dual-energy computed tomography generates standard diagnostic imaging and lung perfusion analysis. • Depiction of CPE on central arteries relies on standard diagnostic imaging. • Detection of peripheral CPE is improved by perfusion imaging.

Effects of Eurocollins solution as aortic flush for the procurement of human pancreas.

PubMed

Gonzalez, Adriano M; Filho, Gaspar J Lopes; Pestana, José O M; Linhares, Marcelo M; Silva, Maria Helena G; Moura, Rita Maria A M; Melaragno, Cláudio; de Sá, João Roberto; Rangel, Erica B; Trivino, Tarcisio

2005-11-15

Belzer solution is considered to be the best preservation media used for pancreas transplantation; however, its high cost accounts for approximately 14.5% of all resources allocated by the Brazilian government toward each pancreatic transplant. The objective of the present study was to test a reduction of Belzer solution during pancreas harvest, thereby lowering procedural cost. The patients received pancreas-kidney transplantations during the period from January 2003 to August 2004. Patients were divided into two groups. Patients assigned to Group A (n=30) received only Belzer solution (2 L through the aorta artery), whereas patients in Group B (n=16) were perfused first with 1 L of Eurocollins solution followed by 1 L of Belzer solution. The two groups were assessed for differences in the following clinical parameters: the need for insulin replacement or antifungal and anticytomegalovirus treatment, pancreatitis, acute cellular rejection, graft vascular thrombosis, fistulas, intra-abdominal collection, graft loss, deaths, pancreatic ischemia time, and average hospitalization time. No statistically significant differences were observed in any of the parameters analyzed (P<0.05). The use of Eurocollins solution, followed by Belzer solution during pancreas harvesting, did not result in differences in graft survival or functionality, postsurgical complications, or patient survival and hospitalization time, when compared to the use of Belzer solution alone. Perfusion with 1 L of Eurocollins solution followed by 1 L of Belzer solution during pancreas harvesting seems to be a simple and efficient alternative for reducing the costs of the harvesting process.

Diagnostic performance of semi-quantitative and quantitative stress CMR perfusion analysis: a meta-analysis.

PubMed

van Dijk, R; van Assen, M; Vliegenthart, R; de Bock, G H; van der Harst, P; Oudkerk, M

2017-11-27

Stress cardiovascular magnetic resonance (CMR) perfusion imaging is a promising modality for the evaluation of coronary artery disease (CAD) due to high spatial resolution and absence of radiation. Semi-quantitative and quantitative analysis of CMR perfusion are based on signal-intensity curves produced during the first-pass of gadolinium contrast. Multiple semi-quantitative and quantitative parameters have been introduced. Diagnostic performance of these parameters varies extensively among studies and standardized protocols are lacking. This study aims to determine the diagnostic accuracy of semi- quantitative and quantitative CMR perfusion parameters, compared to multiple reference standards. Pubmed, WebOfScience, and Embase were systematically searched using predefined criteria (3272 articles). A check for duplicates was performed (1967 articles). Eligibility and relevance of the articles was determined by two reviewers using pre-defined criteria. The primary data extraction was performed independently by two researchers with the use of a predefined template. Differences in extracted data were resolved by discussion between the two researchers. The quality of the included studies was assessed using the 'Quality Assessment of Diagnostic Accuracy Studies Tool' (QUADAS-2). True positives, false positives, true negatives, and false negatives were subtracted/calculated from the articles. The principal summary measures used to assess diagnostic accuracy were sensitivity, specificity, andarea under the receiver operating curve (AUC). Data was pooled according to analysis territory, reference standard and perfusion parameter. Twenty-two articles were eligible based on the predefined study eligibility criteria. The pooled diagnostic accuracy for segment-, territory- and patient-based analyses showed good diagnostic performance with sensitivity of 0.88, 0.82, and 0.83, specificity of 0.72, 0.83, and 0.76 and AUC of 0.90, 0.84, and 0.87, respectively. In per territory analysis our results show similar diagnostic accuracy comparing anatomical (AUC 0.86(0.83-0.89)) and functional reference standards (AUC 0.88(0.84-0.90)). Only the per territory analysis sensitivity did not show significant heterogeneity. None of the groups showed signs of publication bias. The clinical value of semi-quantitative and quantitative CMR perfusion analysis remains uncertain due to extensive inter-study heterogeneity and large differences in CMR perfusion acquisition protocols, reference standards, and methods of assessment of myocardial perfusion parameters. For wide spread implementation, standardization of CMR perfusion techniques is essential. CRD42016040176 .

PGE1, dexamethasone, U-74389G, or Bt2-cAMP as an additive to promote protection by UW solution in I/R injury.

PubMed

Chiang, C H; Hsu, K; Yan, H C; Harn, H J; Chang, D M

1997-08-01

A method to reduce ischemia-reperfusion (I/R) injury can be an important criterion to improve the preservation solution. Although University of Wisconsin solution (UW) works as a lung preservation solution, its attenuation effect on I/R injury has not been investigated. We attempted to determine whether, by adding various protective agents, modified UW solutions will enhance the I/R attenuation by UW. We examined the I/R injury in an isolated rat lung model. Various solutions, e.g., physiological salt solution (PSS), UW, and modified UW solutions containing various protective agents such as prostaglandin E1, dexamethasone, U-74389G, or dibutyryl adenosine 3',5'-cyclic monophosphate were perfused individually to evaluate the I/R injury. Isolated rat lung experiments, with ischemia for 45 min, then reperfusion for 60 min, were conducted in a closed circulating system. Hemodynamic changes, lung weight gain (LWG), capillary filtration coefficient (Kfc), protein content of lavage fluid, concentration of cytokines, and lung histopathology were analyzed. Results showed that the acute I/R lung injury with immediate permeability pulmonary edema was associated with an increase in tumor necrosis factor-alpha (TNF-alpha) production. A significant correlation existed between TNF-alpha and Kfc (r = 0.8, P < 0.0001) and TNF-alpha and LWG (r = 0. 9, P < 0.0001), indicating that TNF-alpha is an important cytokine modulating early I/R injury. Significantly lower levels of Kfc, LWG, TNF-alpha, and protein concentration of lung lavage (P < 0.05) were found in the UW-perfused group than in the control group perfused with PSS. Modified UW promoted the protective effect of UW to further decrease Kfc, LWG, and TNF-alpha (P < 0.05). Histopathological observations also substantiated this evidence. In the UW+U-74389G group, bronchial alveolar lavage fluid contained lowest protein concentration. We conclude that the UW solution attenuates I/R injury of rat lung and that the modified UW solutions further enhance the effect of UW in reducing I/R injury. Among modified solutions, UW+U-74389G is the best. Further investigation of the improved effects of the modified UW solutions would be beneficial in lung transplantation.

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

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.

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.

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

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

PubMed

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

2015-08-01

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

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.

TU-G-204-01: BEST IN PHYSICS (IMAGING): Dynamic CT Myocardial Perfusion Measurement and Its Comparison to Fractional Flow Reserve

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

Ziemer, B; Hubbard, L; Groves, E

2015-06-15

Purpose: To evaluate a first pass analysis (FPA) technique for CT perfusion measurement in a swine animal and its validation using fractional flow reserve (FFR) as a reference standard. Methods: Swine were placed under anesthesia and relevant physiologic parameters were continuously recorded. Intra-coronary adenosine was administered to induce maximum hyperemia. A pressure wire was advanced distal to the first diagonal branch of the left anterior descending (LAD) artery for FFR measurements and a balloon dilation catheter was inserted over the pressure wire into the proximal LAD to create varying levels of stenosis. Images were acquired with a 320-row wide volumemore » CT scanner. Three main coronary perfusion beds were delineated in the myocardium using arteries extracted from CT angiography images using a minimum energy hypothesis. The integrated density in the perfusion bed was used to calculate perfusion using the FPA technique. The perfusion in the LAD bed over a range of stenosis severity was measured. The measured fractional perfusion was compared to FFR and linear regression was performed. Results: The measured fractional perfusion using the FPA technique (P-FPA) and FFR were related as P-FPA = 1.06FFR – 0.06 (r{sup 2} = 0.86). The perfusion measurements were calculated with only three to five total CT volume scans, which drastically reduces the radiation dose as compared with the existing techniques requiring 15–20 volume scans. Conclusion: The measured perfusion using the first pass analysis technique showed good correlation with FFR measurements as a reference standard. The technique for perfusion measurement can potentially make a substantial reduction in radiation dose as compared with the existing techniques.« less

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

PubMed

Goo, Hyun Woo; Park, Sang Hyub

2017-11-01

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

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.

Near-infrared voltage-sensitive fluorescent dyes optimized for optical mapping in blood-perfused myocardium.

PubMed

Matiukas, Arvydas; Mitrea, Bogdan G; Qin, Maochun; Pertsov, Arkady M; Shvedko, Alexander G; Warren, Mark D; Zaitsev, Alexey V; Wuskell, Joseph P; Wei, Mei-de; Watras, James; Loew, Leslie M

2007-11-01

Styryl voltage-sensitive dyes (e.g., di-4-ANEPPS) have been used successfully for optical mapping in cardiac cells and tissues. However, their utility for probing electrical activity deep inside the myocardial wall and in blood-perfused myocardium has been limited because of light scattering and high absorption by endogenous chromophores and hemoglobin at blue-green excitation wavelengths. The purpose of this study was to characterize two new styryl dyes--di-4-ANBDQPQ (JPW-6003) and di-4-ANBDQBS (JPW-6033)--optimized for blood-perfused tissue and intramural optical mapping. Voltage-dependent spectra were recorded in a model lipid bilayer. Optical mapping experiments were conducted in four species (mouse, rat, guinea pig, and pig). Hearts were Langendorff perfused using Tyrode's solution and blood (pig). Dyes were loaded via bolus injection into perfusate. Transillumination experiments were conducted in isolated coronary-perfused pig right ventricular wall preparations. The optimal excitation wavelength in cardiac tissues (650 nm) was >70 nm beyond the absorption maximum of hemoglobin. Voltage sensitivity of both dyes was approximately 10% to 20%. Signal decay half-life due to dye internalization was 80 to 210 minutes, which is 5 to 7 times slower than for di-4-ANEPPS. In transillumination mode, DeltaF/F was as high as 20%. In blood-perfused tissues, DeltaF/F reached 5.5% (1.8 times higher than for di-4-ANEPPS). We have synthesized and characterized two new near-infrared dyes with excitation/emission wavelengths shifted >100 nm to the red. They provide both high voltage sensitivity and 5 to 7 times slower internalization rate compared to conventional dyes. The dyes are optimized for deeper tissue probing and optical mapping of blood-perfused tissue, but they also can be used for conventional applications.

The effect of rigor mortis on the passage of erythrocytes and fluid through the myocardium of isolated dog hearts.

PubMed

Nevalainen, T J; Gavin, J B; Seelye, R N; Whitehouse, S; Donnell, M

1978-07-01

The effect of normal and artificially induced rigor mortis on the vascular passage of erythrocytes and fluid through isolated dog hearts was studied. Increased rigidity of 6-mm thick transmural sections through the centre of the posterior papillary muscle was used as an indication of rigor. The perfusibility of the myocardium was tested by injecting 10 ml of 1% sodium fluorescein in Hanks solution into the circumflex branch of the left coronary artery. In prerigor hearts (20 minute incubation) fluorescein perfused the myocardium evenly whether or not it was preceded by an injection of 10 ml of heparinized dog blood. Rigor mortis developed in all hearts after 90 minutes incubation or within 20 minutes of perfusing the heart with 50 ml of 5 mM iodoacetate in Hanks solution. Fluorescein injected into hearts in rigor did not enter the posterior papillary muscle and adjacent subendocardium whether or not it was preceded by heparinized blood. Thus the vascular occlusion caused by rigor in the dog heart appears to be so effective that it prevents flow into the subendocardium of small soluble ions such as fluorescein.

Glutathione S-transferase iso-enzymes in perfusate from pumped kidneys are associated with delayed graft function

PubMed Central

Hall, Isaac E.; Bhangoo, Ronik S.; Reese, Peter P.; Doshi, Mona D.; Weng, Francis L.; Hong, Kwangik; Lin, Haiqun; Han, Gang; Hasz, Rick D.; Goldstein, Michael J.; Schröppel, Bernd; Parikh, Chirag R.

2014-01-01

Accurate and reliable assessment tools are needed in transplantation. The objective of this prospective, multicenter study was to determine the associations of the alpha and pi iso-enzymes of glutathione S-transferase (GST), measured from perfusate solution at the start and end (base and post) of kidney allograft machine perfusion, with subsequent delayed graft function (DGF). We also compared GST iso-enzyme perfusate levels from discarded versus transplanted kidneys. A total of 428 kidneys were linked to outcomes as recorded by the United Network of Organ Sharing. DGF, defined as any dialysis in the first week of transplant, occurred in 141 recipients (32%). Alpha and pi-GST levels significantly increased during machine perfusion. The adjusted relative risks (95% confidence interval) of DGF with each log-unit increase in base and post pi-GST were 1.14 (1.0-1.28) and 1.33 (1.02-1.72), respectively. Alpha-GST was not independently associated with DGF. There were no significant differences in GST values between discarded and transplanted kidneys, though renal resistance was significantly higher in discarded kidneys. We found pi-GST at the end of machine perfusion to be independently associated with DGF. Further studies should elucidate the utility of GST for identifying injured kidneys with regard to organ allocation, discard and recipient management decisions. PMID:24612768

The secretion of alkali metal ions by the perfused cat pancreas as influenced by the composition and osmolality of the external environment and by inhibitors of metabolism and Na+, K+-ATPase activity

PubMed Central

Case, R. M.; Scratcherd, T.

1974-01-01

1. The secretion of sodium, potassium and lithium has been studied in the isolated cat pancreas, perfused with bicarbonate buffered saline solutions of varying composition and osmolality, and stimulated maximally with secretin. 2. Under isosmolal conditions, when perfusate sodium chloride was replaced by sucrose, sodium secretion and potassium secretion were directly related to perfusate sodium concentration, [Na]p. 3. When osmolality was varied by increasing or decreasing perfusate sodium chloride concentration, the secretion of sodium and of potassium were maximal at [Na]p of about 120 and 80 mM respectively. 4. At a given [Na]p, sodium secretion was greater under hypo-osmolal conditions than under isosmolal conditions. 5. When potassium concentration was varied over the range 0-130 mM under isosmolal conditions, by adjusting perfusate NaCl concentration, the secretion of potassium and of sodium were maximal at [K]p of about 50 and 10 mM respectively. Water flux was maximal at a [K]p of 10-15 mM. The concentration of potassium in the secretion was almost identical with that in the perfusate over the whole concentration range. 6. Replacement of perfusate sodium by lithium reduced the volume of secretion, though a small secretion was maintained even in the complete absence of sodium. The concentration of lithium in the secretion was generally slightly greater than that in the perfusate. 7. Omission of potassium from the perfusate reduced secretion by about 65%. Rubidium was a complete substitute for potassium; caesium was not. 8. Energy for secretion is derived largely from oxidative phosphorylation. Secretion was reduced by more than 90% under anaerobic conditions and in the presence of dinitrophenol or cyanide. Removal of glucose from the perfusate reduced secretion by more than 50% within 30 min; lactate was a complete substitute for glucose. 9. Ouabain, ethacrinic acid and frusimide, known inhibitors of Na+, K+-ATPase activity, all inhibited pancreatic electrolyte secretion. 10. The observations are interpreted with reference to the nature of active transport processes involved in pancreatic electrolyte secretion. PMID:4281836

Sialic acids regulate microvessel permeability, revealed by novel in vivo studies of endothelial glycocalyx structure and function

PubMed Central

Betteridge, Kai B.; Arkill, Kenton P.; Neal, Christopher R.; Harper, Steven J.; Foster, Rebecca R.; Satchell, Simon C.; Bates, David O.

2017-01-01

Key points We have developed novel techniques for paired, direct, real‐time in vivo quantification of endothelial glycocalyx structure and associated microvessel permeability.Commonly used imaging and analysis techniques yield measurements of endothelial glycocalyx depth that vary by over an order of magnitude within the same vessel.The anatomical distance between maximal glycocalyx label and maximal endothelial cell plasma membrane label provides the most sensitive and reliable measure of endothelial glycocalyx depth.Sialic acid residues of the endothelial glycocalyx regulate glycocalyx structure and microvessel permeability to both water and albumin. Abstract The endothelial glycocalyx forms a continuous coat over the luminal surface of all vessels, and regulates multiple vascular functions. The contribution of individual components of the endothelial glycocalyx to one critical vascular function, microvascular permeability, remains unclear. We developed novel, real‐time, paired methodologies to study the contribution of sialic acids within the endothelial glycocalyx to the structural and functional permeability properties of the same microvessel in vivo. Single perfused rat mesenteric microvessels were perfused with fluorescent endothelial cell membrane and glycocalyx labels, and imaged with confocal microscopy. A broad range of glycocalyx depth measurements (0.17–3.02 μm) were obtained with different labels, imaging techniques and analysis methods. The distance between peak cell membrane and peak glycocalyx label provided the most reliable measure of endothelial glycocalyx anatomy, correlating with paired, numerically smaller values of endothelial glycocalyx depth (0.078 ± 0.016 μm) from electron micrographs of the same portion of the same vessel. Disruption of sialic acid residues within the endothelial glycocalyx using neuraminidase perfusion decreased endothelial glycocalyx depth and increased apparent solute permeability to albumin in the same vessels in a time‐dependent manner, with changes in all three true vessel wall permeability coefficients (hydraulic conductivity, reflection coefficient and diffusive solute permeability). These novel technologies expand the range of techniques that permit direct studies of the structure of the endothelial glycocalyx and dependent microvascular functions in vivo, and demonstrate that sialic acid residues within the endothelial glycocalyx are critical regulators of microvascular permeability to both water and albumin. PMID:28524373

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.

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.

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.

Sub-band denoising and spline curve fitting method for hemodynamic measurement in perfusion MRI

NASA Astrophysics Data System (ADS)

Lin, Hong-Dun; Huang, Hsiao-Ling; Hsu, Yuan-Yu; Chen, Chi-Chen; Chen, Ing-Yi; Wu, Liang-Chi; Liu, Ren-Shyan; Lin, Kang-Ping

2003-05-01

In clinical research, non-invasive MR perfusion imaging is capable of investigating brain perfusion phenomenon via various hemodynamic measurements, such as cerebral blood volume (CBV), cerebral blood flow (CBF), and mean trasnit time (MTT). These hemodynamic parameters are useful in diagnosing brain disorders such as stroke, infarction and periinfarct ischemia by further semi-quantitative analysis. However, the accuracy of quantitative analysis is usually affected by poor signal-to-noise ratio image quality. In this paper, we propose a hemodynamic measurement method based upon sub-band denoising and spline curve fitting processes to improve image quality for better hemodynamic quantitative analysis results. Ten sets of perfusion MRI data and corresponding PET images were used to validate the performance. For quantitative comparison, we evaluate gray/white matter CBF ratio. As a result, the hemodynamic semi-quantitative analysis result of mean gray to white matter CBF ratio is 2.10 +/- 0.34. The evaluated ratio of brain tissues in perfusion MRI is comparable to PET technique is less than 1-% difference in average. Furthermore, the method features excellent noise reduction and boundary preserving in image processing, and short hemodynamic measurement time.

Effect of perfusion temperature on glucose and electrolyte transport during hyperthermic intraperitoneal chemoperfusion (HIPEC) with oxaliplatin.

PubMed

Ceelen, W; De Somer, F; Van Nieuwenhove, Y; Vande Putte, D; Pattyn, P

2013-07-01

Hyperthermic intraperitoneal chemoperfusion (HIPEC) with oxaliplatin is increasingly used in patients with carcinomatosis from colorectal cancer. For reasons of chemical stability, oxaliplatin can only be administered in a dextrose (D5%) solution, and this causes peroperative glucose and electrolyte shifts. Here, we examined the influence of perfusion temperature on glucose and electrolyte transport, metabolic shifts, and surgical morbidity. Patients with carcinomatosis underwent cytoreduction and HIPEC using oxaliplatin (460 mg/m(2) in D5%, open abdomen) during 30 min at 39°-41 °C. Intraperitoneal (IP) temperature was measured at three locations using thermocouple probes. The area under the temperature versus time curve (AUCt) was calculated using the trapezoid rule. The influence of perfusion temperature on surgical outcome was assessed using linear regression models and the Mann Whitney U test where appropriate. From July 2005 until March 2011, 145 procedures were performed in 139 patients with a diagnosis of CRC (70%), pseudomyxoma peritonei (11%), ovarian cancer (10%), or miscellaneous peritoneal malignancies (9%). Postoperative mortality and major morbidity were 1.4% and 26%, respectively. Higher perfusion temperature was related to more pronounced changes in serum glucose (P = 0.058), sodium (P = 0.017), and lactate (P < 0.001). The median duration of nasogastric drainage was 5 days, and this was unrelated to perfusion temperature (P = 0.76). The GI fistula rate and reoperation rate were 12.4% and 16.5% respectively; neither was related to perfusion temperature. In patients undergoing HIPEC with oxaliplatin, perfusion temperature exacerbates peroperative metabolic shifts but does not affect surgical outcome. Copyright © 2012 Elsevier Ltd. All rights reserved.

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.

Rotating Rod Renewable Microcolumns for Automated, Solid-Phase DNA Hybridization

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

Bruckner-Lea, Cynthia J.; Stottlemyre, Mark R.; Holman, David A.

1999-12-01

The development of a new temperature-controlled renewable microcolumn flow cell for solid-phase nucleic acid analysis in a sequential injection system is described. The flow cell includes a stepper motor-driven rotating rod with the working end cut to a 45 degree angle. In one position, the end of the rod prevents passage of microbeads while allowing fluid flow; rotation of the rod by 180 degrees release the beads. This system was used to rapidly test many hybridization and elution protocols to examine the temperature and solution conditions required for sequence specific nucleic acid hybridization. Target nucleic acids labeled with a near-infraredmore » fluorescent dye were detected immediately post-column using a flow-through fluorescence detector, with a detection limit of 40 pM dye concentration at a flow rate of 5 mu l/s. Temperature control of the column and the presence of Triton X-100 surfactant were critical for specific hybridization. Perfusion of the column with complementary oligonucleotide (200 mu l, 10nM) resulted in hybridization with 8% of the DNA binding sites on the microbeads with a solution residence time of less than a second and a total sample perfusion time of 40 seconds. The use of the renewable column system for detection of an unlabeled PCR product in a sandwich assay was also demonstrated.« less

Water and solute absorption from carbohydrate-electrolyte solutions in the human proximal small intestine: a review and statistical analysis.

PubMed

Shi, Xiaocai; Passe, Dennis H

2010-10-01

The purpose of this study is to summarize water, carbohydrate (CHO), and electrolyte absorption from carbohydrate-electrolyte (CHO-E) solutions based on all of the triple-lumen-perfusion studies in humans since the early 1960s. The current statistical analysis included 30 reports from which were obtained information on water absorption, CHO absorption, total solute absorption, CHO concentration, CHO type, osmolality, sodium concentration, and sodium absorption in the different gut segments during exercise and at rest. Mean differences were assessed using independent-samples t tests. Exploratory multiple-regression analyses were conducted to create prediction models for intestinal water absorption. The factors influencing water and solute absorption are carefully evaluated and extensively discussed. The authors suggest that in the human proximal small intestine, water absorption is related to both total solute and CHO absorption; osmolality exerts various impacts on water absorption in the different segments; the multiple types of CHO in the ingested CHO-E solutions play a critical role in stimulating CHO, sodium, total solute, and water absorption; CHO concentration is negatively related to water absorption; and exercise may result in greater water absorption than rest. A potential regression model for predicting water absorption is also proposed for future research and practical application. In conclusion, water absorption in the human small intestine is influenced by osmolality, solute absorption, and the anatomical structures of gut segments. Multiple types of CHO in a CHO-E solution facilitate water absorption by stimulating CHO and solute absorption and lowering osmolality in the intestinal lumen.

MRI quantification of diffusion and perfusion in bone marrow by intravoxel incoherent motion (IVIM) and non-negative least square (NNLS) analysis.

PubMed

Marchand, A J; Hitti, E; Monge, F; Saint-Jalmes, H; Guillin, R; Duvauferrier, R; Gambarota, G

2014-11-01

To assess the feasibility of measuring diffusion and perfusion fraction in vertebral bone marrow using the intravoxel incoherent motion (IVIM) approach and to compare two fitting methods, i.e., the non-negative least squares (NNLS) algorithm and the more commonly used Levenberg-Marquardt (LM) non-linear least squares algorithm, for the analysis of IVIM data. MRI experiments were performed on fifteen healthy volunteers, with a diffusion-weighted echo-planar imaging (EPI) sequence at five different b-values (0, 50, 100, 200, 600 s/mm2), in combination with an STIR module to suppress the lipid signal. Diffusion signal decays in the first lumbar vertebra (L1) were fitted to a bi-exponential function using the LM algorithm and further analyzed with the NNLS algorithm to calculate the values of the apparent diffusion coefficient (ADC), pseudo-diffusion coefficient (D*) and perfusion fraction. The NNLS analysis revealed two diffusion components only in seven out of fifteen volunteers, with ADC=0.60±0.09 (10(-3) mm(2)/s), D*=28±9 (10(-3) mm2/s) and perfusion fraction=14%±6%. The values obtained by the LM bi-exponential fit were: ADC=0.45±0.27 (10(-3) mm2/s), D*=63±145 (10(-3) mm2/s) and perfusion fraction=27%±17%. Furthermore, the LM algorithm yielded values of perfusion fraction in cases where the decay was not bi-exponential, as assessed by NNLS analysis. The IVIM approach allows for measuring diffusion and perfusion fraction in vertebral bone marrow; its reliability can be improved by using the NNLS, which identifies the diffusion decays that display a bi-exponential behavior. Copyright © 2014 Elsevier Inc. All rights reserved.

From "Gut Feeling" to Objectivity: Machine Preservation of the Liver as a Tool to Assess Organ Viability.

PubMed

Watson, Christopher J E; Jochmans, Ina

2018-01-01

The purpose of this review was to summarise how machine perfusion could contribute to viability assessment of donor livers. In both hypothermic and normothermic machine perfusion, perfusate transaminase measurement has allowed pretransplant assessment of hepatocellular damage. Hypothermic perfusion permits transplantation of marginal grafts but as yet has not permitted formal viability assessment. Livers undergoing normothermic perfusion have been investigated using parameters similar to those used to evaluate the liver in vivo. Lactate clearance, glucose evolution and pH regulation during normothermic perfusion seem promising measures of viability. In addition, bile chemistry might inform on cholangiocyte viability and the likelihood of post-transplant cholangiopathy. While the use of machine perfusion technology has the potential to reduce and even remove uncertainty regarding liver graft viability, analysis of large datasets, such as those derived from large multicenter trials of machine perfusion, are needed to provide sufficient information to enable viability parameters to be defined and validated .

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.

Laser speckle contrast imaging identifies ischemic areas on gastric tube reconstructions following esophagectomy

PubMed Central

Milstein, Dan M.J.; Ince, Can; Gisbertz, Suzanne S.; Boateng, Kofi B.; Geerts, Bart F.; Hollmann, Markus W.; van Berge Henegouwen, Mark I.; Veelo, Denise P.

2016-01-01

Abstract Gastric tube reconstruction (GTR) is a high-risk surgical procedure with substantial perioperative morbidity. Compromised arterial blood supply and venous congestion are believed to be the main etiologic factors associated with early and late anastomotic complications. Identifying low blood perfusion areas may provide information on the risks of future anastomotic leakage and could be essential for improving surgical techniques. The aim of this study was to generate a method for gastric microvascular perfusion analysis using laser speckle contrast imaging (LSCI) and to test the hypothesis that LSCI is able to identify ischemic regions on GTRs. Patients requiring elective laparoscopy-assisted GTR participated in this single-center observational investigation. A method for intraoperative evaluation of blood perfusion and postoperative analysis was generated and validated for reproducibility. Laser speckle measurements were performed at 3 different time pointes, baseline (devascularized) stomach (T0), after GTR (T1), and GTR at 20° reverse Trendelenburg (T2). Blood perfusion analysis inter-rater reliability was high, with intraclass correlation coefficients for each time point approximating 1 (P < 0.0001). Baseline (T0) and GTR (T1) mean blood perfusion profiles were highest at the base of the stomach and then progressively declined towards significant ischemia at the most cranial point or anastomotic tip (P < 0.01). After GTR, a statistically significant improvement in mean blood perfusion was observed in the cranial gastric regions of interest (P < 0.05). A generalized significant decrease in mean blood perfusion was observed across all GTR regions of interest during 20° reverse Trendelenburg (P < 0.05). It was feasible to implement LSCI intraoperatively to produce blood perfusion assessments on intact and reconstructed whole stomachs. The analytical design presented in this study resulted in good reproducibility of gastric perfusion measurements between different investigators. LSCI provides spatial and temporal information on the location of adequate tissue perfusion and may thus be an important aid in optimizing surgical and anesthesiological procedures for strategically selecting anastomotic site in patients undergoing esophagectomy with GTR. PMID:27336874

Laser speckle contrast imaging identifies ischemic areas on gastric tube reconstructions following esophagectomy.

PubMed

Milstein, Dan M J; Ince, Can; Gisbertz, Suzanne S; Boateng, Kofi B; Geerts, Bart F; Hollmann, Markus W; van Berge Henegouwen, Mark I; Veelo, Denise P

2016-06-01

Gastric tube reconstruction (GTR) is a high-risk surgical procedure with substantial perioperative morbidity. Compromised arterial blood supply and venous congestion are believed to be the main etiologic factors associated with early and late anastomotic complications. Identifying low blood perfusion areas may provide information on the risks of future anastomotic leakage and could be essential for improving surgical techniques. The aim of this study was to generate a method for gastric microvascular perfusion analysis using laser speckle contrast imaging (LSCI) and to test the hypothesis that LSCI is able to identify ischemic regions on GTRs.Patients requiring elective laparoscopy-assisted GTR participated in this single-center observational investigation. A method for intraoperative evaluation of blood perfusion and postoperative analysis was generated and validated for reproducibility. Laser speckle measurements were performed at 3 different time pointes, baseline (devascularized) stomach (T0), after GTR (T1), and GTR at 20° reverse Trendelenburg (T2).Blood perfusion analysis inter-rater reliability was high, with intraclass correlation coefficients for each time point approximating 1 (P < 0.0001). Baseline (T0) and GTR (T1) mean blood perfusion profiles were highest at the base of the stomach and then progressively declined towards significant ischemia at the most cranial point or anastomotic tip (P < 0.01). After GTR, a statistically significant improvement in mean blood perfusion was observed in the cranial gastric regions of interest (P < 0.05). A generalized significant decrease in mean blood perfusion was observed across all GTR regions of interest during 20° reverse Trendelenburg (P < 0.05).It was feasible to implement LSCI intraoperatively to produce blood perfusion assessments on intact and reconstructed whole stomachs. The analytical design presented in this study resulted in good reproducibility of gastric perfusion measurements between different investigators. LSCI provides spatial and temporal information on the location of adequate tissue perfusion and may thus be an important aid in optimizing surgical and anesthesiological procedures for strategically selecting anastomotic site in patients undergoing esophagectomy with GTR.

Direct estimation of mass flow and diffusion of nitrogen compounds in solution and soil.

PubMed

Oyewole, Olusegun Ayodeji; Inselsbacher, Erich; Näsholm, Torgny

2014-02-01

Plant nutrient uptake from soil is mainly governed by diffusion and transpirationally induced mass flow, but the current methods for assessing the relative importance of these processes are indirect. We developed a microdialysis method using solutions of different osmotic potentials as perfusates to simulate diffusion and mass flow processes, and assessed how induced mass flow affected fluxes of nitrogen (N) compounds in solution and in boreal forest soil. Varying the osmotic potential of perfusates induced vertical fluxes in the direction of the dialysis membranes at rates of between 1 × 10(-8) and 3 × 10(-7)  m s(-1) , thus covering the estimated range of water velocities perpendicular to root surfaces and induced by transpiration. Mass flow increased N fluxes in solution but even more so in soil. This effect was explained by an indirect effect of mass flow on rates of diffusive fluxes, possibly caused by the formation of steeper gradients in concentrations of N compounds from membrane surfaces out in the soil. Our results suggest that transpiration may be an essential driver of plant N acquisition. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

Effect of TNF-alpha blockade on coagulopathy and endothelial cell activation in xenoperfused porcine kidneys.

PubMed

Ramackers, Wolf; Klose, Johannes; Tiede, Andreas; Werwitzke, Sonja; Rataj, Dennis; Friedrich, Lars; Johanning, Kai; Vondran, Florian W R; Bergmann, Sabine; Schuettler, Wolfgang; Bockmeyer, Clemens Luitpold; Becker, Jan Ulrich; Klempnauer, Jürgen; Winkler, Michael

2015-01-01

Following pig-to-primate kidney transplantation, endothelial cell activation and xenogenic activation of the recipient's coagulation eventually leading to organ dysfunction and microthrombosis can be observed. In this study, we examined the effect of a TNF-receptor fusion protein (TNF-RFP) on endothelial cell activation and coagulopathy utilizing an appropriate ex vivo perfusion system. Using an ex vivo perfusion circuit based on C1-Inhibitor (C1-Inh) and low-dose heparin administration, we have analyzed consumptive coagulopathy following contact of human blood with porcine endothelium. Porcine kidneys were recovered following in situ cold perfusion with Histidine-tryptophan-ketoglutarate (HTK) organ preservation solution and were immediately connected to a perfusion circuit utilizing freshly drawn pooled porcine or human AB blood. The experiments were performed in three individual groups: autologous perfusion (n = 5), xenogenic perfusion without any further pharmacological intervention (n = 10), or with addition of TNF-RFP (n = 5). After perfusion, tissue samples were obtained for real-time PCR and immunohistological analyses. Endothelial cell activation was assessed by measuring the expression levels of E-selectin, ICAM-1, and VCAM-1. Kidney survival during organ perfusion with human blood, C1-Inh, and heparin, but without any further pharmacological intervention was 126 ± 78 min. Coagulopathy was observed with significantly elevated concentrations of D-dimer and thrombin-antithrombin complex (TAT), resulting in the formation of multiple microthrombi. Endothelial cell activation was pronounced, as shown by increased expression of E-selectin and VCAM-1. In contrast, pharmacological intervention with TNF-RFP prolonged organ survival to 240 ± 0 min (max. perfusion time; no difference to autologous control). Formation of microthrombi was slightly reduced, although not significantly, if compared to the xenogenic control. D-dimer and TAT were elevated at similar levels to the xenogenic control experiments. In contrast, endothelial cell activation, as shown by real-time PCR, was significantly reduced in the TNF-RFP group. We conclude that although coagulopathy was not affected, TNF-RFP is able to suppress inflammation occurring after xenoperfusion in this ex vivo perfusion model. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Assessment of Tissue Perfusion Following Conventional Liposuction of Perforator-Based Abdominal Flaps

PubMed Central

Saçak, Bülent; Yalçın, Doğuş; Pilancı, Özgür; Tuncer, Fatma Betül; Çelebiler, Özhan

2017-01-01

Background The effect of liposuction on the perforators of the lower abdominal wall has been investigated in several studies. There are controversial results in the literature that have primarily demonstrated the number and patency of the perforators. The aim of this study was to determine the effect of liposuction on the perfusion of perforator-based abdominal flaps using a combined laser–Doppler spectrophotometer (O2C, Oxygen to See, LEA Medizintechnik). Methods Nine female patients undergoing classical abdominoplasty were included in the study. Perforators and the perfusion zones of the deep inferior epigastric artery flap were marked on the patient's abdominal wall. Flap perfusion was quantitatively assessed by measuring blood flow, velocity, capillary oxygen saturation, and relative amount of hemoglobin for each zone preoperatively, after tumescent solution infiltration, following elevation of the flap on a single perforator, and after deep and superficial liposuction, respectively. Results The measurements taken after elevation of the flap were not significantly different than measurements taken after the liposuction procedures. Conclusions The liposuction procedure does not significantly alter the perfusion of perforator-based abdominal flaps in the early period. The abdominal tissue discarded in a classic abdominoplasty operation can be raised as a perforator flap and has been demonstrated to be a unique model for clinical research. PMID:28352599

Development and Evaluation of Heartbeat: A Machine Perfusion Heart Preservation System.

PubMed

Li, Yongnan; Zeng, Qingdong; Liu, Gang; Du, Junzhe; Gao, Bingren; Wang, Wei; Zheng, Zhe; Hu, Shengshou; Ji, Bingyang

2017-11-01

Static cold storage is accompanied with a partial safe ischemic interval for donor hearts. In this current study, a machine perfusion system was built to provide a better preservation for the donor heart and assessment for myocardial function. Chinese mini-swine (weight 30-35 kg, n = 16) were randomly divided into HTK, Celsior, and Heartbeat groups. All donor hearts were respectively preserved for 8 hours under static cold storage or machine perfusion. The perfusion solution is aimed to maintain its homeostasis based on monitoring the Heartbeat group. The ultrastructure of myocardium suggests better myocardial protection in the Heartbeat group compared with HTK or Celsior-preserved hearts. The myocardial and coronary artery structural and functional integrity was evaluated by immunofluorescence and Western blots in the Heartbeat. In the Heartbeat group, donor hearts maintained a high adenosine triphosphate level. Bcl-2 and Beclin-1 protein demonstrates high expression in the Celsior group. The Heartbeat system can be used to preserve donor hearts, and it could guarantee the myocardial and endothelial function of hearts during machine perfusion. Translating Heartbeat into clinical practice, it is such as to impact on donor heart preservation for cardiac transplantation. © 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Pharmacokinetic evaluation of intrapleural perfusion with hyperthermic chemotherapy using cisplatin in patients with malignant pleural effusion.

PubMed

Sakaguchi, Hirozo; Ishida, H; Nitanda, H; Yamazaki, N; Kaneko, K; Kobayashi, Kunihiko

2017-02-01

Malignant pleural effusion (MPE) has a poor prognosis. Most patients are treated with tube thoracostomy and sclerotherapy, although its success rate is around 64%. We have investigated intrapleural perfusion with hyperthermic chemotherapy (IPHC) using cisplatin in a study with a pharmacokinetic evaluation. Patients with MPE, performance status of 0-1, possibility of good lung expansion and Cr<1.2mg/dL were treated with IPHC. The circuit was filled with 2000mL of normal saline containing cisplatin at a dose of 80mg/m 2 . Under video-assisted thoracoscopic surgery, the thoracic cavity was filled and perfused at a speed of approximately 1L/min at a temperature of 43°C for 1h. Perfusion solution and plasma samples were periodically collected, and concentrations of protein-unbound (free) platinum, which was the active derivative of cisplatin, and total platinum were determined by flameless atomic absorption spectrometry. Twenty patients with MPE (8 lung cancers, 7 mesotheliomas, and 5 others) were enrolled in this study. Rate of free platinum concentration relative to total platinum concentration in perfusion solution after 1hr IPHC at 43°C was 61.1±12.9%. Area under curve (AUC) of free platinum in the pleural space was calculated to be 26.3μg/mLxh, resulting in complete control of pleural effusion for 3 months after IHPC in all cases (95% confidence interval: 83-100%). While, absorption rate of total platinum from the pleural space was 33.8±17.0% (27.4±13.6mg/m 2 ), and the maximum concentration of total platinum in serum was low, 0.66±0.31μg/mL, resulting in controllable side effects; grade 1 renal toxicity: 6 patients, grade 1 emesis: 7 patients. IPHC with cisplatin showed favorable pharmacokinetic profiles for an optional treatment to control malignant pleural effusion. Copyright © 2016 The Author(s). Published by Elsevier B.V. All rights reserved.

Endogenous calcitonin gene-related peptide (CGRP) mediates adrenergic-dependent vasodilation induced by nicotine in mesenteric resistance arteries of the rat

PubMed Central

Shiraki, Hinako; Kawasaki, Hiromu; Tezuka, Satoko; Nakatsuma, Akira; Kurosaki, Yuji

2000-01-01

The mechanisms underlying vasodilator effect of nicotine on mesenteric resistance blood vessels and the role of calcitonin gene-related peptide (CGRP)-containing (CGRPergic) vasodilator nerves were studied in the rat. Mesenteric vascular beds isolated from Wistar rats were perfused with Krebs solution, and perfusion pressure was measured with a pressure transducer. In preparations with intact endothelium and contracted by perfusion with Krebs solution containing methoxamine, perfusion of nicotine (1–100 μM) for 1 min caused a concentration-dependent vasodilator response without vasoconstriction. The nicotine-induced vasodilation was markedly inhibited by hexamethonium (nicotinic cholinoceptor antagonist, 10 μM) and blocked by guanethidine (adrenergic neuron blocker, 5 μM). Either denervation by cold storage (4°C for 72 h) or adrenergic denervation by 6-hydroxydopamine (toxin for adrenergic neurons, 2 mM for 20 min incubation, twice) blocked the nicotine-induced vasodilation. Neither endothelium removal with perfusion of sodium deoxycholate (1.80 mg ml−1, for 30 s) nor treatment with Nω-nitro-L-arginine (nitric oxide synthase inhibitor, 100 μM), atropine (muscarinic cholinoceptor antagonist, 10 nM) or propranolol (β-adrenoceptor antagonist, 100 nM) affected the nicotine-induced vasodilation. In preparations without endothelium, treatment with capsaicin (depleting CGRP-containing sensory nerves, 1 μM) or human CGRP[8–37] (CGRP receptor antagonist, 0.5 μM) markedly inhibited the nicotine-induced vasodilation. These results suggest that, in the mesenteric resistance artery of the rat, nicotine induces vasodilation, which is independent of the function of the endothelium and is involved in activation of CGRPergic nerves. It is also suggested that nicotine stimulates presynaptic nicotinic cholinoceptors on adrenergic nerves to release adrenergic neurotransmitters, which then act on CGRPergic nerves to release endogenous CGRP from the nerve. PMID:10882393

Osmotic effects of polyethylene glycol.

PubMed

Schiller, L R; Emmett, M; Santa Ana, C A; Fordtran, J S

1988-04-01

Polyethylene glycol (PEG) has been used to increase the osmotic pressure of fluids used to cleanse the gastrointestinal tract. However, little is known about its osmotic activity. To investigate this activity systematically, solutions of PEG of differing molecular weights were made and subjected to measurement of osmolality by both freezing point depression and vapor pressure osmometry. Measured osmolality was increasingly greater than predicted from average molecular weight as PEG concentration increased. Measurement of sodium activity in NaCl/PEG solutions by means of an ion-selective electrode suggested that the higher than expected osmolality could be due in part to interactions that, in effect, sequestered water from the solution. Osmolality was consistently greater by freezing point osmometry than by vapor pressure osmometry. To determine which osmometry method reflected biologically relevant osmolality, normal subjects underwent steady-state total gut perfusion with an electrolyte solution containing 105 g/L of PEG 3350. This produced rectal effluent that was hypertonic by freezing point osmometry but isotonic by vapor pressure osmometry. Assuming that luminal fluid reaches osmotic equilibrium with plasma during total gut perfusion, this result suggests that the vapor pressure osmometer accurately reflects the biologically relevant osmolality of intestinal contents. We conclude that PEG exerts more of an osmotic effect than would be predicted from its molecular weight. This phenomenon may reflect interactions between PEG and water molecules that alter the physical chemistry of the solution and sequester water from the solution.

[Study on intestinal absorption features of oligosaccharides in Morinda officinalis How. with sigle-pass perfusion].

PubMed

Deng, Shao-Dong; Zhang, Peng; Lin, Li; Xiao, Feng-Xia; Lin, Jing-Ran

2015-01-01

To study the in situ intestinal absorption of five oligosaccharides contained in Morinda officinalis How. (sucrose, kestose, nystose, 1F-Fructofuranosyinystose and Bajijiasu). The absorption of the five oligosaccharides in small intestine (duodenum, jejunum and ileum) and colon of rats and their contents were investigated by using in situ single-pass perfusion model and HPLC-ELSD. The effects of drug concentration, pH in perfusate and P-glycoprotein inhibitor on the intestinal absorption were investigated to define the intestinal absorption mechanism of the five oligosaccharides in rats. According to the results, all of the five oligosaccharides were absorbed in the whole intestine, and their absorption rates were affected by the pH of the perfusion solution, drug concentration and intestinal segments. Verapamil Hydrochloride could significantly increase the absorptive amount of sucrose and Bajijiasu, suggesting sucrose and Bajijiasu are P-gp's substrate. The five oligosaccharides are absorbed mainly through passive diffusion in the intestinal segments, without saturated absorption. They are absorbed well in all intestines and mainly in duodenum and jejunum.

Glutathione S-transferase iso-enzymes in perfusate from pumped kidneys are associated with delayed graft function.

PubMed

Hall, I E; Bhangoo, R S; Reese, P P; Doshi, M D; Weng, F L; Hong, K; Lin, H; Han, G; Hasz, R D; Goldstein, M J; Schröppel, B; Parikh, C R

2014-04-01

Accurate and reliable assessment tools are needed in transplantation. The objective of this prospective, multi-center study was to determine the associations of the alpha and pi iso-enzymes of glutathione S-transferase (GST), measured from perfusate solution at the start and end (base and post) of kidney allograft machine perfusion, with subsequent delayed graft function (DGF). We also compared GST iso-enzyme perfusate levels from discarded versus transplanted kidneys. A total of 428 kidneys were linked to outcomes as recorded by the United Network of Organ Sharing. DGF, defined as any dialysis in the first week of transplant, occurred in 141 recipients (32%). Alpha- and pi-GST levels significantly increased during machine perfusion. The adjusted relative risks (95% confidence interval) of DGF with each log-unit increase in base and post pi-GST were 1.14 (1.0-1.3) and 1.36 (1.1-1.8), respectively. Alpha-GST was not independently associated with DGF. There were no significant differences in GST values between discarded and transplanted kidneys, though renal resistance was significantly higher in discarded kidneys. We found pi-GST at the end of machine perfusion to be independently associated with DGF. Further studies should elucidate the utility of GST for identifying injured kidneys with regard to organ allocation, discard and recipient management decisions. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.

Rewarming preservation by organ perfusion system for donation after cardiac death liver grafts in pigs.

PubMed

Matsuno, N; Obara, H; Watanabe, R; Iwata, S; Kono, S; Fujiyama, M; Hirano, T; Kanazawa, H; Enosawa, S

2014-05-01

Use of grafts from donors after cardiac death (DCD) would greatly contribute to the expansion of the donor organ pool. However, this requires the development of novel preservation methods to recover the organ from changes due to warm ischemia time (WIT). Porcine livers were perfused with a newly developed machine perfusion (MP) system. The livers were perfused with modified University of Wisconsin solution (UW) - gluconate. All grafts were procured after acute hemorrhagic shock with the ventilator off. For group 1 (n = 6), grafts were procured after WIT of 60 minutes and preserved by hypothermic MP (HMP) for 3 hours. For group 2 (n = 5), grafts were preserved with 2 hours of simple cold storage (SCS) and HMP for 2 hours. For group 3 (n = 6), grafts were preserved with 2 hours of SCS and rewarming up to 25°C by MP for 2 hours (RMP). The preserved liver grafts were transplanted orthotopically. The alanine aminotransferase level in perfusate in RMP during perfusion preservation was maintained at less than that of HMP. The levels of aspartate aminotransferase and lactate dehydrogenase in the 2 hours after reperfusion were significantly lower in group 3. Histologically, the necrosis of hepatocytes was less severe in group 3. The survival rate in group 3 was 2/4, but 0/4 in the other group. RMP is expected to facilitate the recovery of the DCD liver grafts. Copyright © 2014 Elsevier Inc. All rights reserved.

Intralipid minimizes hepatocytes injury after anoxia-reoxygenation in an ex vivo rat liver model.

PubMed

Stadler, Michaela; Nuyens, Vincent; Boogaerts, Jean G

2007-01-01

Ischemia-reperfusion injury is a determinant in liver injury occurring during surgical procedures, ischemic states, and multiple organ failure. The pre-existing nutritional status of the liver, i.e., fasting, might contribute to the extent of tissue injury. This study investigated whether Intralipid, a solution containing soybean oil, egg phospholipids, and glycerol, could protect ex vivo perfused livers of fasting rats from anoxia-reoxygenation injury. The portal vein was cannulated, and the liver was removed and perfused in a closed ex vivo system. Isolated livers were perfused with glucose 5.5 and 15 mM, and two different concentrations of Intralipid, i.e., 0.5:100 and 1:100 (v/v) Intralipid 10%:medium (n = 5 in each group). The experiment consisted of perfusion for 15 min, warm anoxia for 60 min, and reoxygenation during 60 min. Hepatic enzymes, potassium, glucose, lactate, bilirubin, dienes, trienes, and cytochrome-c were analyzed in perfusate samples. The proportion of glycogen in hepatocytes was determined in biopsies. Intralipid attenuated transaminases, lactate dehydrogenase, potassium, diene, and triene release in the perfusate (dose-dependant) during the reoxygenation phase when compared with glucose-treated groups. The concentration of cytochrome-c in the medium was the highest in the 5.5-mM glucose group. The glycogen content was low in all livers at the start of the experiment. Intralipid presents, under the present experimental conditions, a better protective effect than glucose in anoxia-reoxygenation injury of the rat liver.

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 perfusions, which is valuable for the early diagnosis of certain brain diseases, e.g. multiple sclerosis.« less

Increasing the reliability of solution exchanges by monitoring solenoid valve actuation.

PubMed

Auzmendi, Jerónimo Andrés; Moffatt, Luciano

2010-01-15

Solenoid valves are a core component of most solution perfusion systems used in neuroscience research. As they open and close, they control the flow of solution through each perfusion line, thereby modulating the timing and sequence of chemical stimulation. The valves feature a ferromagnetic plunger that moves due to the magnetization of the solenoid and returns to its initial position with the aid of a spring. The delays between the time of voltage application or removal and the actual opening or closing of the valve are difficult to predict beforehand and have to be measured experimentally. Here we propose a simple method for monitoring whether and when the solenoid valve opens and closes. The proposed method detects the movement of the plunger as it generates a measurable signal on the solenoid that surrounds it. Using this plunger signal, we detected the opening and closing of diaphragm and pinch solenoid valves with a systematic error of less than 2ms. After this systematic error is subtracted, the trial-to-trial error was below 0.2ms.

Stability and compatibility of the mixture of tramadol, ketorolac, metoclopramide and ranitidine in a solution for intravenous perfusion.

PubMed

Cabrera, J; Mancuso, M; Cabrera-Fránquiz, F; Limiñana, J; Díez, A

2011-01-01

To determine whether a mixture for intravenous perfusion containing tramadol (5 mg/ml), ranitidine (1.5 mg/ml), ketorolac (1.5 mg/ml) and metoclopramide (0.5 mg/ml) in a 0.9% sodium chlorides solution is compatible and stable at room temperature during a 48-hour period. We tested the mixture for stability using the HPLC technique (high performance liquid chromatography), with parallel visual assessments of any changes in colour, appearance of precipitate or phase separation indicating incompatibilities between the components. At the end of the trial, chromatography data showed a mean metoclopramide concentration between 100% and 105% of the initial level, while concentrations of tramadol, ketorolac and ranitidine were between 99% and 102% of initial levels. There was no evidence of incompatibility between the drugs at any time during the study period. The combination is stable as a solution and its components are physically and chemically compatible in the concentrations used in the study, during at least 48 hours at room temperature. Copyright © 2008 SEFH. Published by Elsevier Espana. All rights reserved.

Radiotracer Imaging Allows for Noninvasive Detection and Quantification of Abnormalities in Angiosome Foot Perfusion in Diabetic Patients With Critical Limb Ischemia and Nonhealing Wounds

PubMed Central

Alvelo, Jessica L.; Papademetris, Xenophon; Mena-Hurtado, Carlos; Jeon, Sangchoon; Sumpio, Bauer E.; Sinusas, Albert J.

2018-01-01

Background: Single photon emission computed tomography (SPECT)/computed tomography (CT) imaging allows for assessment of skeletal muscle microvascular perfusion but has not been quantitatively assessed in angiosomes, or 3-dimensional vascular territories, of the foot. This study assessed and compared resting angiosome foot perfusion between healthy subjects and diabetic patients with critical limb ischemia (CLI). Additionally, the relationship between SPECT/CT imaging and the ankle–brachial index—a standard tool for evaluating peripheral artery disease—was assessed. Methods and Results: Healthy subjects (n=9) and diabetic patients with CLI and nonhealing ulcers (n=42) underwent SPECT/CT perfusion imaging of the feet. CT images were segmented into angiosomes for quantification of relative radiotracer uptake, expressed as standardized uptake values. Standardized uptake values were assessed in ulcerated angiosomes of patients with CLI and compared with whole-foot standardized uptake values in healthy subjects. Serial SPECT/CT imaging was performed to assess uptake kinetics of technetium-99m-tetrofosmin. The relationship between angiosome perfusion and ankle–brachial index was assessed via correlational analysis. Resting perfusion was significantly lower in CLI versus healthy subjects (P=0.0007). Intraclass correlation coefficients of 0.95 (healthy) and 0.93 (CLI) demonstrated excellent agreement between serial perfusion measurements. Correlational analysis, including healthy and CLI subjects, demonstrated a significant relationship between ankle–brachial index and SPECT/CT (P=0.01); however, this relationship was not significant for diabetic CLI patients only (P=0.2). Conclusions: SPECT/CT imaging assesses regional foot perfusion and detects abnormalities in microvascular perfusion that may be undetectable by conventional ankle–brachial index in patients with diabetes mellitus. SPECT/CT may provide a novel approach for evaluating responses to targeted therapies. PMID:29748311

SPECT Analysis of Cardiac Perfusion Changes After Whole-Breast/Chest Wall Radiation Therapy With or Without Active Breathing Coordinator: Results of a Randomized Phase 3 Trial

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

Zellars, Richard, E-mail: zellari@jhmi.edu; Bravo, Paco E.; Tryggestad, Erik

2014-03-15

Purpose: Cardiac muscle perfusion, as determined by single-photon emission computed tomography (SPECT), decreases after breast and/or chest wall (BCW) irradiation. The active breathing coordinator (ABC) enables radiation delivery when the BCW is farther from the heart, thereby decreasing cardiac exposure. We hypothesized that ABC would prevent radiation-induced cardiac toxicity and conducted a randomized controlled trial evaluating myocardial perfusion changes after radiation for left-sided breast cancer with or without ABC. Methods and Materials: Stages I to III left breast cancer patients requiring adjuvant radiation therapy (XRT) were randomized to ABC or No-ABC. Myocardial perfusion was evaluated by SPECT scans (before andmore » 6 months after BCW radiation) using 2 methods: (1) fully automated quantitative polar mapping; and (2) semiquantitative visual assessment. The left ventricle was divided into 20 segments for the polar map and 17 segments for the visual method. Segments were grouped by anatomical rings (apical, mid, basal) or by coronary artery distribution. For the visual method, 2 nuclear medicine physicians, blinded to treatment groups, scored each segment's perfusion. Scores were analyzed with nonparametric tests and linear regression. Results: Between 2006 and 2010, 57 patients were enrolled and 43 were available for analysis. The cohorts were well matched. The apical and left anterior descending coronary artery segments had significant decreases in perfusion on SPECT scans in both ABC and No-ABC cohorts. In unadjusted and adjusted analyses, controlling for pretreatment perfusion score, age, and chemotherapy, ABC was not significantly associated with prevention of perfusion deficits. Conclusions: In this randomized controlled trial, ABC does not appear to prevent radiation-induced cardiac perfusion deficits.« less

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

Evaluation of mechanical dyssynchrony and myocardial perfusion using phase analysis of gated SPECT imaging in patients with left ventricular dysfunction

PubMed Central

Trimble, Mark A.; Borges-Neto, Salvador; Honeycutt, Emily F.; Shaw, Linda K.; Pagnanelli, Robert; Chen, Ji; Iskandrian, Ami E.; Garcia, Ernest V.; Velazquez, Eric J.

2010-01-01

Background Using phase analysis of gated single photon emission computed tomography (SPECT) imaging, we examined the relation between myocardial perfusion, degree of electrical dyssynchrony, and degree of SPECT-derived mechanical dyssynchrony in patients with left ventricular (LV) dysfunction. Methods and Results We retrospectively examined 125 patients with LV dysfunction and ejection fraction of 35% or lower. Fourier analysis converts regional myocardial counts into a continuous thickening function, allowing resolution of phase of onset of myocardial thickening. The SD of LV phase distribution (phase SD) and histogram bandwidth describe LV phase dispersion as a measure of dyssynchrony. Heart failure (HF) patients with perfusion abnormalities ities have higher degrees of dyssynchrony measured by median phase SD (45.5° vs 27.7°, P < .0001) and bandwidth (117.0° vs 73.0°, P = .0006). HF patients with prolonged QRS durations have higher degrees of dyssynchrony measured by median phase SD (54.1° vs 34.7°, P < .0001) and bandwidth (136.5° vs 99.0°, P = .0005). Mild to moderate correlations exist between QRS duration and phase analysis indices of phase SD (r = 0.50) and bandwidth (r = 0.40). Mechanical dyssynchrony (phase SD >43°) was 43.2%. Conclusions HF patients with perfusion abnormalities or prolonged QRS durations QRS durations have higher degrees of mechanical dyssynchrony. Gated SPECT myocardial perfusion imaging can quantify myocardial function, perfusion, and dyssynchrony and may help in evaluating patients for cardiac resynchronization therapy. PMID:18761269

Detection of dehydration by using volume kinetics.

PubMed

Zdolsek, Joachim; Li, Yuhong; Hahn, Robert G

2012-10-01

Patients admitted to surgery may be dehydrated, which is difficult to diagnose except when it is severe (>5% Gl116 of the body weight). We hypothesized that modest dehydration can be detected by kinetic analysis of the blood hemoglobin concentration after a bolus infusion of crystalloid fluid. Four series of experiments were performed on 10 conscious, healthy male volunteers. Separated by at least 2 days, they received 5 or 10 mL/kg acetated Ringer's solution over 15 minutes. Before starting half of the IV infusions, volume depletion amounting to 1.5 to 2.0 L (approximately 2% of body weight) was induced with furosemide. The elimination clearance and the half-life of the infused fluid were calculated based on blood hemoglobin over 120 minutes. The perfusion index and the pleth variability index were monitored by pulse oximetry after a change of body position. Dehydration decreased the elimination clearance of acetated Ringer's solution [median (25th-75th percentile)] from 1.84 (1.23-2.57) to 0.53 (0.41-0.79) mL/kg/min (Wilcoxon matched-pair test P < 0.001) and increased the half-life from 23 (12-37) to 76 (57-101) minutes (P < 0.001). The smaller infusion, 5 mL/kg, fully discriminated between experiments performed in the euhydrated and dehydrated states, whereas the urinary excretion provided a less-reliable indication of hydration status. Dehydration decreased the perfusion index but did not affect the pleth variability index. Dehydration amounting to 2% of the body weight could be detected from the elimination clearance and the half-life of an infusion of 5 mL/kg Ringer's solution.

Histogram Analysis of CT Perfusion of Hepatocellular Carcinoma for Predicting Response to Transarterial Radioembolization: Value of Tumor Heterogeneity Assessment.

PubMed

Reiner, Caecilia S; Gordic, Sonja; Puippe, Gilbert; Morsbach, Fabian; Wurnig, Moritz; Schaefer, Niklaus; Veit-Haibach, Patrick; Pfammatter, Thomas; Alkadhi, Hatem

2016-03-01

To evaluate in patients with hepatocellular carcinoma (HCC), whether assessment of tumor heterogeneity by histogram analysis of computed tomography (CT) perfusion helps predicting response to transarterial radioembolization (TARE). Sixteen patients (15 male; mean age 65 years; age range 47-80 years) with HCC underwent CT liver perfusion for treatment planning prior to TARE with Yttrium-90 microspheres. Arterial perfusion (AP) derived from CT perfusion was measured in the entire tumor volume, and heterogeneity was analyzed voxel-wise by histogram analysis. Response to TARE was evaluated on follow-up imaging (median follow-up, 129 days) based on modified Response Evaluation Criteria in Solid Tumors (mRECIST). Results of histogram analysis and mean AP values of the tumor were compared between responders and non-responders. Receiver operating characteristics were calculated to determine the parameters' ability to discriminate responders from non-responders. According to mRECIST, 8 patients (50%) were responders and 8 (50%) non-responders. Comparing responders and non-responders, the 50th and 75th percentile of AP derived from histogram analysis was significantly different [AP 43.8/54.3 vs. 27.6/34.3 mL min(-1) 100 mL(-1)); p < 0.05], while the mean AP of HCCs (43.5 vs. 27.9 mL min(-1) 100 mL(-1); p > 0.05) was not. Further heterogeneity parameters from histogram analysis (skewness, coefficient of variation, and 25th percentile) did not differ between responders and non-responders (p > 0.05). If the cut-off for the 75th percentile was set to an AP of 37.5 mL min(-1) 100 mL(-1), therapy response could be predicted with a sensitivity of 88% (7/8) and specificity of 75% (6/8). Voxel-wise histogram analysis of pretreatment CT perfusion indicating tumor heterogeneity of HCC improves the pretreatment prediction of response to TARE.

[Non-invasive assessment of the perfusion of wounds using power Doppler imaging: vacuum assisted closure versus direct wound closure].

PubMed

Jungius, K P; Chilla, B K; Labler, L; Teodorovic, N; Marincek, B

2006-10-01

The goal of our study was to assess the perfusion in wounds treated by vacuum assisted closure (VAC) compared to primary wound closure. Power Doppler Ultrasound (PDUS) was carried out under standardised conditions in 15 VAC-treated and 10 primarily closed wounds as well as on altogether 25 intraindividual reference areas. All data were sent to a work station for post-processing to determine the perfused area. Statistical data analysis was performed with the Mann-Whitney test. Both VAC-treated wounds and primarily closed wounds showed a significant increase of the perfusion when compared to the intraindividual reference area (p < 0.0001). In VAC-treated wounds, a markedly increased perfusion was measured compared to the wounds closed primarily (p < 0.0001). Perfusion decreased during treatment, but in two VAC-treated wounds, an initial increase of the perfusion was observed. Both these wounds were grossly infected. PDUS allows the quantification of the differences in wound perfusion. This can be helpful in the detection of progressive local wound infections.

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.

Machine perfusion preservation of the non-heart-beating donor rat livers using polysol, a new preservation solution.

PubMed

Bessems, M; Doorschodt, B M; van Vliet, A K; van Gulik, T M

2005-01-01

The increasing shortage of donor organs has led to a focus on extended criteria donors, including the non-heart-beating donor (NHBD). An optimal preservation method is required to facilitate successful transplantation of these ischemically damaged organs. The recent literature has shown clear advantages of hypothermic machine perfusion (MP) over cold storage (CS). For MP, modified University of Wisconsin perfusion solution (UW-G) is often used, which, however, is known to cause microcirculatory obstruction, is difficult to obtain, and is expensive. Therefore, Polysol was developed as a MP preservation solution that contains specific nutrients for the liver, such as amino acids, energy substrates, and vitamins. The aim of this study was to compare Polysol with UW-G in a NHBD rat liver model. After 24 hours hypothermic MP of NHBD rat livers using UW-G or Polysol, liver damage and function parameters were assessed during 60 minutes of reperfusion with Krebs-Henseleit buffer. Control livers were reperfused after 24 hours CS in UW. Liver enzyme release was significantly higher among the CS-UW group compared to MP using UW-G or Polysol. Flow during reperfusion was significantly higher when using Polysol compared to UW-G. Bile production and ammonia clearance were highest when using Polysol compared to UW-G. There was less cellular edema after preservation with Polysol compared to UW-G. MP of NHBD rat livers for 24 hours using UW-G or Polysol resulted in less hepatocellular damage than CS in UW. MP of NHBD livers for 24 hours using Polysol is superior to MP using UW-G.

Nonspecific microvascular vasodilation during iontophoresis is attenuated by application of hyperosmolar saline.

PubMed

Asberg, A; Holm, T; Vassbotn, T; Andreassen, A K; Hartmann, A

1999-07-01

Iontophoretic administration of acetylcholine chloride (ACh) and sodium nitroprusside (SNP) combined with laser Doppler skin blood perfusion measurements are used for determination of endothelial-dependent and -independent vasodilation. However, the method is biased by nonspecific vasodilation. The primary aim of this study was to investigate if iontophoresis-induced nonspecific vasodilation may be attenuated by addition of high molar concentrations of NaCl to the iontophoresis solutions. Secondary we investigated the applicability of 5 mol/liter NaCl solution as vehicle for ACh and SNP in this method. Skin perfusion changes were determined for iontophoresis of pure vehicles, deionized water and 5 mol/liter NaCl solution, in 12 healthy volunteers. Responses in skin perfusion to iontophoresis of ACh and SNP dissolved in both vehicles were also investigated. Addition of 5 mol/liter NaCl to deionized water significantly attenuated the nonspecific vasodilation and lowered the potential applied over the skin. The inter- and intraindividual coefficients of variation to ACh and SNP responses became, however, higher using hyperosmolar vehicle. During iontophoresis of SNP (in deionized water) we were unable to distinguish between SNP and vehicle effects. This study shows that the nonspecific vasodilation induced by iontophoresis can be attenuated by addition of 5 mol/liter NaCl, possibly due to lower electrical potential over the skin. However, the variability of the method was not improved. When deionized water was used as vehicle the effect of SNP could not be differentiated from that of the vehicle. This was not the case for ACh. Copyright 1999 Academic Press.

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-brain study. The need for performing CT perfusion study also in the emergency setting could represent a problem for physicians who are not used to interpreting the parametric maps (CBV, MTT etc.). The software-generated maps could be of value in these settings, helping the less expert physician in the differentiation between different areas.

Measurement of myocardial perfusion and infarction size using computer-aided diagnosis system for myocardial contrast echocardiography.

PubMed

Du, Guo-Qing; Xue, Jing-Yi; Guo, Yanhui; Chen, Shuang; Du, Pei; Wu, Yan; Wang, Yu-Hang; Zong, Li-Qiu; Tian, Jia-Wei

2015-09-01

Proper evaluation of myocardial microvascular perfusion and assessment of infarct size is critical for clinicians. We have developed a novel computer-aided diagnosis (CAD) approach for myocardial contrast echocardiography (MCE) to measure myocardial perfusion and infarct size. Rabbits underwent 15 min of coronary occlusion followed by reperfusion (group I, n = 15) or 60 min of coronary occlusion followed by reperfusion (group II, n = 15). Myocardial contrast echocardiography was performed before and 7 d after ischemia/reperfusion, and images were analyzed with the CAD system on the basis of eliminating particle swarm optimization clustering analysis. The myocardium was quickly and accurately detected using contrast-enhanced images, myocardial perfusion was quantitatively calibrated and a color-coded map calibrated by contrast intensity and automatically produced by the CAD system was used to outline the infarction region. Calibrated contrast intensity was significantly lower in infarct regions than in non-infarct regions, allowing differentiation of abnormal and normal myocardial perfusion. Receiver operating characteristic curve analysis documented that -54-pixel contrast intensity was an optimal cutoff point for the identification of infarcted myocardium with a sensitivity of 95.45% and specificity of 87.50%. Infarct sizes obtained using myocardial perfusion defect analysis of original contrast images and the contrast intensity-based color-coded map in computerized images were compared with infarct sizes measured using triphenyltetrazolium chloride staining. Use of the proposed CAD approach provided observers with more information. The infarct sizes obtained with myocardial perfusion defect analysis, the contrast intensity-based color-coded map and triphenyltetrazolium chloride staining were 23.72 ± 8.41%, 21.77 ± 7.8% and 18.21 ± 4.40% (% left ventricle) respectively (p > 0.05), indicating that computerized myocardial contrast echocardiography can accurately measure infarct size. On the basis of the results, we believe the CAD method can quickly and automatically measure myocardial perfusion and infarct size and will, it is hoped, be very helpful in clinical therapeutics. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Effects of angiotensin II type 1 receptor antagonist and temperature on prolonged cardioplegic arrest in neonatal rat myocytes.

PubMed

Lucchese, Gianluca; Cambi, Giulia Elisa; De Rita, Fabrizio; Franzoi, Mauro; Faggian, Giuseppe; Mazzucco, Alessandro; Modesti, Pietro Amedeo; Luciani, Giovanni Battista

2013-08-01

Cardioplegic arrest is a model of ischemia/reperfusion injury and results in the death of irreplaceable cardiac myocytes by a programmed cell death or apoptosis. Signal transducers and activators of transcription (STAT) signaling pathways play an important role in the modulation of apoptosis after ischemia and reperfusion. Angiotensin II type 1 (AT1) receptor antagonist added to cardioplegia could represent an additional modality for enhancing myocardial protection during cardioplegic arrest. To test that hypothesis, we studied the effect of AT1 receptor antagonism and cardioplegia temperature perfusion on STATs modulation during cardioplegic arrest in neonatal rat hearts. Isolated, nonworking hearts (n = 4 per group) from neonatal rats were perfused aerobically in the Langendorff mode according to the following scheme: Dulbecco's Modified Eagle's Medium solution (Group 1); cold (4°C) modified St. Thomas' Hospital no. 2 (MSTH2) cardioplegic solution (Group 2); cold (4°C) MSTH2 cardioplegic solution plus AT1 antagonist (Valsartan) (Group 3); and warm (34°C) MSTH2 cardioplegic solution (Group 4). Thus, myocytes were isolated by enzymatic digestion, and STAT1, STAT2, STAT3, and STAT5 were investigated in Western blot studies. Times to arrest after cardioplegia were 6-10 s for all groups with the exception of Group 1 (spontaneous arrest after 12-16 s). Total cardioplegia delivery volume was about 300 mL in 15 min. Perfusion with cold MSTH2 supplemented with AT1 receptor antagonist (Group 3) induced a significant reduction in STAT1, STAT2, and STAT5 tyrosine phosphorylation versus other groups (P < 0.05). The decreased activation of STAT1, STAT2, and STAT5 observed in Group 3 was accompanied by reduction of interleukin-1β (P < 0.05). On the other hand, STAT3 activation was significantly reduced in Groups 1 and 4 (P < 0.05). Only perfusion with AT1 receptor antagonist supplemented with cold MSTH2 significantly decreases the inflammatory response of the neonatal rat cardiomyocytes without affecting antiapoptotic influence provided by activation of STAT3. Therefore, AT1 receptor antagonist could play a pivotal role in cytoprotective effect and cardiac recovery in neonates and infants. © 2013, Copyright the Authors. Artificial Organs © 2013 Wiley Periodicals, Inc. and International Center for Artificial Organs and Transplantation.

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.

Electroosmotic Push–Pull Perfusion: Description and Application to Qualitative Analysis of the Hydrolysis of Exogenous Galanin in Organotypic Hippocampal Slice Cultures

PubMed Central

2013-01-01

We demonstrate here a method that perfuses a small region of an organotypic hippocampal culture with a solution containing an enzyme substrate, a neuropeptide. Perfusate containing hydrolysis products is continually collected and subsequently analyzed for the products of the enzymatic degradation of the peptide substrate. The driving force for perfusion is an electric field. The fused silica capillaries used as “push” and “pull” or “source” and “collection” capillaries have a ζ-potential that is negative and greater in magnitude than the tissue’s ζ-potential. Thus, depending on the magnitudes of particular dimensions, the electroosmotic flow in the capillaries augments the fluid velocity in the tissue. The flow rate is not directly measured; however, we determine it using a finite-element approach. We have determined the collection efficiency of the system using an all d-amino acid internal standard. The flow rates are low, in the nL/min range, and adjustable by controlling the current or voltage in the system. The collection efficiency of the d-amino acid peptide internal standard is variable, increasing with increased current and thus electroosmotic flow rate. The collection efficiency can be rationalized in the context of a Peclet number. Electroosmotic push–pull perfusion of the neuropeptide galanin (gal1–29) through the extracellular space of an organotypic hippocampal culture results in its hydrolysis by ectopeptidase reactions occurring in the extracellular space. The products of hydrolysis were identified by MALDI-MS. Experiments at two levels of current (8–12 μA and 19–40 μA) show that the probability of seeing hydrolysis products (apparently from aminopeptidases) is greater in the Cornu Ammonis area 3 (CA3) than in the Cornu Ammonis area 1 (CA1) in the higher current experiments. In the lower current experiments, shorter peptide products of aminopeptidases (gal13–29 to gal20–19) are seen with greater frequency in CA3 than in CA1 but there is no statistically significant difference for longer peptides (gal3–29 to gal12–29). PMID:23614879

Quantitative Assessment of Free Flap Viability with CEUS Using an Integrated Perfusion Software.

PubMed

Geis, S; Klein, S; Prantl, L; Dolderer, J; Lamby, P; Jung, E-M

2015-12-01

New treatment strategies in oncology and trauma surgery lead to an increasing demand for soft tissue reconstruction with free tissue transfer. In previous studies, CEUS was proven to detect early flap failure. The aim of this study was to detect and quantify vascular disturbances after free flap transplantation using a fast integrated perfusion software tool. From 2011 to 2013, 33 patients were examined by one experienced radiologist using CEUS after a bolus injection of 1-2.4 ml of SonoVue(®). Flap perfusion was analysed qualitatively regarding contrast defects or delayed wash-in. Additionally, an integrated semi-quantitative analysis using time-intensity curve analysis (TIC) was performed. TIC analysis of the transplant was conducted on a centimetre-by-centimetre basis up to a penetration depth of 4 cm. The 2 perfusion parameters "Time to PEAK" and "Area under the Curve" were compared in patients without complications vs. patients with minor complications or complete flap loss to figure out significant differences. TtoPk is given in seconds (s) and Area is given in relative units (rU) Results: A regular postoperative process was observed in 26 (79%) patients. In contrast, 5 (15%) patients with partial superficial flap necrosis, 1 patient (3%) with complete flap loss and 1 patient (3%) with haematoma were observed. TtoPk revealed no significant differences, whereas Area revealed significantly lower perfusion values in the corresponding areas in patients with complications. The critical threshold for sufficient flap perfusion was set below 150 rU. In conclusion, CEUS is a mobile and cost-effective opportunity to quantify tissue perfusion and can even be used almost without any restrictions in multi-morbid patients with renal and hepatic failure. © Georg Thieme Verlag KG Stuttgart · New York.

The role of PET quantification in cardiovascular imaging.

PubMed

Slomka, Piotr; Berman, Daniel S; Alexanderson, Erick; Germano, Guido

2014-08-01

Positron Emission Tomography (PET) has several clinical and research applications in cardiovascular imaging. Myocardial perfusion imaging with PET allows accurate global and regional measurements of myocardial perfusion, myocardial blood flow and function at stress and rest in one exam. Simultaneous assessment of function and perfusion by PET with quantitative software is currently the routine practice. Combination of ejection fraction reserve with perfusion information may improve the identification of severe disease. The myocardial viability can be estimated by quantitative comparison of fluorodeoxyglucose ( 18 FDG) and rest perfusion imaging. The myocardial blood flow and coronary flow reserve measurements are becoming routinely included in the clinical assessment due to enhanced dynamic imaging capabilities of the latest PET/CT scanners. Absolute flow measurements allow evaluation of the coronary microvascular dysfunction and provide additional prognostic and diagnostic information for coronary disease. Standard quantitative approaches to compute myocardial blood flow from kinetic PET data in automated and rapid fashion have been developed for 13 N-ammonia, 15 O-water and 82 Rb radiotracers. The agreement between software methods available for such analysis is excellent. Relative quantification of 82 Rb PET myocardial perfusion, based on comparisons to normal databases, demonstrates high performance for the detection of obstructive coronary disease. New tracers, such as 18 F-flurpiridaz may allow further improvements in the disease detection. Computerized analysis of perfusion at stress and rest reduces the variability of the assessment as compared to visual analysis. PET quantification can be enhanced by precise coregistration with CT angiography. In emerging clinical applications, the potential to identify vulnerable plaques by quantification of atherosclerotic plaque uptake of 18 FDG and 18 F-sodium fluoride tracers in carotids, aorta and coronary arteries has been demonstrated.

Impact of patient-specific factors, irradiated left ventricular volume, and treatment set-up errors on the development of myocardial perfusion defects after radiation therapy for left-sided breast cancer

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

Evans, Elizabeth S.; Prosnitz, Robert G.; Yu Xiaoli

2006-11-15

Purpose: The aim of this study was to assess the impact of patient-specific factors, left ventricle (LV) volume, and treatment set-up errors on the rate of perfusion defects 6 to 60 months post-radiation therapy (RT) in patients receiving tangential RT for left-sided breast cancer. Methods and Materials: Between 1998 and 2005, a total of 153 patients were enrolled onto an institutional review board-approved prospective study and had pre- and serial post-RT (6-60 months) cardiac perfusion scans to assess for perfusion defects. Of the patients, 108 had normal pre-RT perfusion scans and available follow-up data. The impact of patient-specific factors onmore » the rate of perfusion defects was assessed at various time points using univariate and multivariate analysis. The impact of set-up errors on the rate of perfusion defects was also analyzed using a one-tailed Fisher's Exact test. Results: Consistent with our prior results, the volume of LV in the RT field was the most significant predictor of perfusion defects on both univariate (p = 0.0005 to 0.0058) and multivariate analysis (p = 0.0026 to 0.0029). Body mass index (BMI) was the only significant patient-specific factor on both univariate (p = 0.0005 to 0.022) and multivariate analysis (p = 0.0091 to 0.05). In patients with very small volumes of LV in the planned RT fields, the rate of perfusion defects was significantly higher when the fields set-up 'too deep' (83% vs. 30%, p = 0.059). The frequency of deep set-up errors was significantly higher among patients with BMI {>=}25 kg/m{sup 2} compared with patients of normal weight (47% vs. 28%, p = 0.068). Conclusions: BMI {>=}25 kg/m{sup 2} may be a significant risk factor for cardiac toxicity after RT for left-sided breast cancer, possibly because of more frequent deep set-up errors resulting in the inclusion of additional heart in the RT fields. Further study is necessary to better understand the impact of patient-specific factors and set-up errors on the development of RT-induced perfusion defects.« less

Sodium, phosphate, glucose, bicarbonate, and alanine interactions in the isolated proximal convoluted tubule of the rabbit kidney.

PubMed

Dennis, V W; Brazy, P C

1978-08-01

Interactions among the transport systems involved with sodium, bicarbonate, glucose, phosphate, and alanine absorption in isolated segments of the rabbit proximal convoluted tubule were examined with radioisotopic techniques to measure glucose, phosphate, and fluid absorption rates. The composition of the perfusate and bath varied from normal, physiological fluids to fluids deficient in a single solute. The deletion of glucose from the perfusate increased the lumen-to-bath flux of phosphate from 5.51 +/- 1.15 to 8.32 +/- 1.34 pmol/mm-min (P less than 0.01). Similar changes occurred when glucose transport was inhibited by phlorizin 10 micron in the perfusate, The deletion of alanine from the perfusate increased the lumen-to-bath flux of phosphate from 6.55 +/- 1.08 to 9.00 +/- 1.30 pmol/mm-min (P less than 0.01) but did not affect glucose transport significantly, 80.1 +/- 10.1 vs. 72.5 +/- 5.4 pmol/mm-min. Replacement of intraluminal sodium with choline, elimination of potassium from the bath, and removal of bicarbonate from the lumen and bath each reduced glucose, phosphate, and fluid absorption. These data indicate that the proximal absorptive processes for glucose and for phosphate include elements that are dependent upon some function of sodium transport. Additionally, the effects on phosphate transport of deleting glucose or alanine occur independent of any changes in net sodium transport and are opposite the effects of deleting bicarbonate. These differences may relate to the observations that the transport of glucose and alanine is electrogenic while that of bicarbonate is not. Regardless of possible mechanisms, the data demonstrate that important changes in the absorption rates of different solutes handled significantly by the proximal convoluted tubule may occur in response to changes in specific components of proximal sodium transport.

The selective cyclooxygenase-2 inhibitor parecoxib markedly improves the ability of the duodenum to regulate luminal hypertonicity in anaesthetized rats.

PubMed

Sedin, J; Sjöblom, M; Nylander, O

2012-07-01

To examine whether the prevention of post-operative duodenal ileus by treatment with parecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, affects the ability of the duodenum to respond to luminal hypertonicity. The proximal duodenums of anaesthetized rats were perfused with hypertonic NaCl solutions with osmolalities of 400, 500, 600 or 700 mOsm kg(-1) , and the effects on mucosal permeability, motility, transepithelial net fluid flux and effluent osmolality were assessed in the absence (control) and presence of parecoxib. Parecoxib-treated, but not control animals, exhibited duodenal contractions, which were reduced by the nicotinic receptor antagonists mecamylamine and hexamethonium and by perfusion with 700 mOsm kg(-1) . All animals responded to luminal hypertonicity with induction of net fluid secretion, which peaked at an osmolality of 500 mOsm kg(-1) . The hypertonicity-induced increases in fluid secretion were twofold greater in parecoxib-treated than in control rats and attenuated by nicotinic receptor blockade. The decrease in luminal osmolality correlated with the osmolality of the perfusion solution in both control and parecoxib-treated animals but the osmolality-adjusting capability was markedly better in the latter group. Rats exposed to duodenal luminal distension responded to hypertonicity with a greater fluid secretion and a larger decrease in luminal osmolality than control rats. Perfusion with 700 mOsm kg(-1) increased mucosal permeability in parecoxib-treated animals only, an effect abolished by nicotinic receptor blockade. Parecoxib markedly improved the ability of the duodenum to sense and to decrease luminal hypertonicity by a mechanism most probably involving inhibition of COX-2 and stimulation of nicotinic acetylcholine receptors. © 2012 The Authors Acta Physiologica © 2012 Scandinavian Physiological Society.

In Vivo MR Imaging of Pulmonary Perfusion and Gas Exchange in Rats via Continuous Extracorporeal Infusion of Hyperpolarized 129Xe

PubMed Central

Cleveland, Zackary I.; Möller, Harald E.; Hedlund, Laurence W.; Nouls, John C.; Freeman, Matthew S.; Qi, Yi; Driehuys, Bastiaan

2012-01-01

Background Hyperpolarized (HP) 129Xe magnetic resonance imaging (MRI) permits high resolution, regional visualization of pulmonary ventilation. Additionally, its reasonably high solubility (>10%) and large chemical shift range (>200 ppm) in tissues allow HP 129Xe to serve as a regional probe of pulmonary perfusion and gas transport, when introduced directly into the vasculature. In earlier work, vascular delivery was accomplished in rats by first dissolving HP 129Xe in a biologically compatible carrier solution, injecting the solution into the vasculature, and then detecting HP 129Xe as it emerged into the alveolar airspaces. Although easily implemented, this approach was constrained by the tolerable injection volume and the duration of the HP 129Xe signal. Methods and Principal Findings Here, we overcome the volume and temporal constraints imposed by injection, by using hydrophobic, microporous, gas-exchange membranes to directly and continuously infuse 129Xe into the arterial blood of live rats with an extracorporeal (EC) circuit. The resulting gas-phase 129Xe signal is sufficient to generate diffusive gas exchange- and pulmonary perfusion-dependent, 3D MR images with a nominal resolution of 2×2×2 mm3. We also show that the 129Xe signal dynamics during EC infusion are well described by an analytical model that incorporates both mass transport into the blood and longitudinal relaxation. Conclusions Extracorporeal infusion of HP 129Xe enables rapid, 3D MR imaging of rat lungs and, when combined with ventilation imaging, will permit spatially resolved studies of the ventilation-perfusion ratio in small animals. Moreover, EC infusion should allow 129Xe to be delivered elsewhere in the body and make possible functional and molecular imaging approaches that are currently not feasible using inhaled HP 129Xe. PMID:22363613

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

PubMed

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

2015-01-01

Fluorescence videography is a promising technique for assessing bowel perfusion. Fluorescence-based enhanced reality (FLER) is a novel concept, in which a dynamic perfusion cartogram, generated by computer analysis, is superimposed on to real-time laparoscopic images. The aim of this experimental study was to assess the accuracy of FLER in detecting differences in perfusion in a small bowel resection-anastomosis model. A small bowel ischaemic segment was created laparoscopically in 13 pigs. Animals were allocated to having anastomoses performed at either low perfusion (25 per cent; n = 7) or high perfusion (75 per cent; n = 6), as determined by FLER analysis. Capillary lactate levels were measured in blood samples obtained by serosal puncturing in the ischaemic area, resection lines and vascularized areas. Pathological inflammation scoring of the anastomosis was carried out. Lactate levels in the ischaemic area (mean(s.d.) 5·6(2·8) mmol/l) were higher than those in resection lines at 25 per cent perfusion (3·7(1·7) mmol/l; P = 0·010) and 75 per cent perfusion (2·9(1·3) mmol/l; P < 0·001), and higher than levels in vascular zones (2·5(1·0) mmol/l; P < 0·001). Lactate levels in resection lines with 75 per cent perfusion were lower than those in lines with 25 per cent perfusion (P < 0·001), and similar to those in vascular zones (P = 0·188). Levels at resection lines with 25 per cent perfusion were higher than those in vascular zones (P = 0·001). Mean(s.d.) global inflammation scores were higher in the 25 per cent perfusion group compared with the 75 per cent perfusion group for mucosa/submucosa (2·1(0·4) versus 1·2(0·4); P = 0·003) and serosa (1·8(0·4) versus 0·8(0·8); P = 0·014). A ratio of preanastomotic lactate levels in the ischaemic area relative to the resection lines of 2 or less was predictive of a more severe inflammation score. In an experimental model, FLER appeared accurate in discriminating bowel perfusion levels. Surgical relevance Clinical assessment has limited accuracy in evaluating bowel perfusion before anastomosis. Fluorescence videography estimates intestinal perfusion based on the fluorescence intensity of injected fluorophores, which is proportional to bowel vascularization. However, evaluation of fluorescence intensity remains a static and subjective measure. Fluorescence-based enhanced reality (FLER) is a dynamic fluorescence videography technique integrating near-infrared endoscopy and specific software. The software generates a virtual perfusion cartogram based on time to peak fluorescence, which can be superimposed on to real-time laparoscopic images. This experimental study demonstrates the accuracy of FLER in detecting differences in bowel perfusion in a survival model of laparoscopic small bowel resection-anastomosis, based on biochemical and histopathological data. It is concluded that real-time imaging of bowel perfusion is easy to use and accurate, and should be translated into clinical use. © 2015 BJS Society Ltd. Published by John Wiley & Sons Ltd.

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

Stress Cardiac MRI in Women With Myocardial Infarction and Nonobstructive Coronary Artery Disease.

PubMed

Mauricio, Rina; Srichai, Monvadi B; Axel, Leon; Hochman, Judith S; Reynolds, Harmony R

2016-10-01

In a prospective study, cardiac MRI (CMR) and intravascular ultrasound were performed in women with myocardial infarction (MI) and nonobstructive coronary artery disease (MINOCA). Forty participants underwent adenosine-stress CMR (sCMR). Abnormal perfusion may co-localize with ischemic late gadolinium enhancement (LGE) and T2-weighted signal hyperintensity (T2+), suggesting microvascular dysfunction contributed to MI. Qualitative perfusion analysis was performed by 2 independent readers. Abnormal myocardial perfusion reserve index (MPRI) was defined as global average ≤1.84. Abnormal rest perfusion was present in 10 patients (25%) and stress perfusion abnormalities in 25 (63%). Abnormal stress perfusion was not associated with LGE but tended to occur with T2+. Among patients with abnormal perfusion and LGE, the LGE pattern was ischemic in half. The locations of abnormal perfusion and LGE matched in 75%, T2+ in 100%. Abnormal stress perfusion was not associated with plaque disruption and matched in location in 63%. MPRI was abnormal in 10 patients (25%) and was not associated with LGE, T2+ or plaque disruption. Abnormal perfusion on sCMR is common among women with MINOCA. Abnormal perfusion usually co-localized with LGE and/or T2+ when present. Variability in LGE pattern leads to uncertainty about whether the finding of abnormal perfusion was cause or consequence of the tissue state leading to LGE. Low MPRI, possibly indicating diffuse microvascular disease, was observed with and without LGE and T2+. Multiple mechanisms may lead to abnormal perfusion on sCMR. Microvascular dysfunction may contribute to the pathogenesis of and coexist with other causes of MINOCA. © 2016 Wiley Periodicals, Inc.

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.

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.

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 secretion into milk, BK, together with its precursor and tissue kallikrein, is continuously released into the vasculature of the isolated, perfused, lactating bovine udder. PMID:12181294

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.

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

Dynamic perfusion CT in brain tumors.

PubMed

Yeung, Timothy Pok Chi; Bauman, Glenn; Yartsev, Slav; Fainardi, Enrico; Macdonald, David; Lee, Ting-Yim

2015-12-01

Dynamic perfusion CT (PCT) is an imaging technique for assessing the vascular supply and hemodynamics of brain tumors by measuring blood flow, blood volume, and permeability-surface area product. These PCT parameters provide information complementary to histopathologic assessments and have been used for grading brain tumors, distinguishing high-grade gliomas from other brain lesions, differentiating true progression from post-treatment effects, and predicting prognosis after treatments. In this review, the basic principles of PCT are described, and applications of PCT of brain tumors are discussed. The advantages and current challenges, along with possible solutions, of PCT are presented. Copyright © 2015. Published by Elsevier Ireland Ltd.

Radio-frequency lesioning in brain tissue with coagulation-dependent thermal conductivity: modelling, simulation and analysis of parameter influence and interaction.

PubMed

Johansson, Johannes D; Eriksson, Ola; Wren, Joakim; Loyd, Dan; Wårdell, Karin

2006-09-01

Radio-frequency brain lesioning is a method for reducing e.g. symptoms of movement disorders. A small electrode is used to thermally coagulate malfunctioning tissue. Influence on lesion size from thermal and electric conductivity of the tissue, microvascular perfusion and preset electrode temperature was investigated using a finite-element model. Perfusion was modelled as an increased thermal conductivity in non-coagulated tissue. The parameters were analysed using a 2(4)-factorial design (n=16) and quadratic regression analysis (n=47). Increased thermal conductivity of the tissue increased lesion volume, while increased perfusion decreased it since coagulation creates a thermally insulating layer due to the cessation of blood perfusion. These effects were strengthened with increased preset temperature. The electric conductivity had negligible effect. Simulations were found realistic compared to in vivo experimental lesions.

Intestinal absorption of 5 chromium compounds in young black ducks (Anas rubripes)

USGS Publications Warehouse

Eastin, W.C.; Haseltine, S.D.; Murray, H.C.

1980-01-01

An in vivo intestinal perfusion technique was used to measure the absorption rates of five Cr compounds in black ducks. Cr was absorbed from saline solutions of KCr(SO4 )2 and CrO3 at a rate about 1.5 to 2.0 times greater than from solutions of Cr, Cr(NO3 )3, and Cr(C5H7O2)3. These results suggest the ionic form of Cr in solution may be an important factor in determining absorption of Cr compounds from the small intestine.

Energy status of pig donor organs after ischemia is independent of donor type.

PubMed

Stadlbauer, Vanessa; Stiegler, Philipp; Taeubl, Philipp; Sereinigg, Michael; Puntschart, Andreas; Bradatsch, Andrea; Curcic, Pero; Seifert-Held, Thomas; Zmugg, Gerda; Stojakovic, Tatjana; Leopold, Barbara; Blattl, Daniela; Horki, Vera; Mayrhauser, Ursula; Wiederstein-Grasser, Iris; Leber, Bettina; Jürgens, Günther; Tscheliessnigg, Karlheinz; Hallström, Seth

2013-04-01

Literature is controversial whether organs from living donors have a better graft function than brain dead (BD) and non-heart-beating donor organs. Success of transplantation has been correlated with high-energy phosphate (HEP) contents of the graft. HEP contents in heart, liver, kidney, and pancreas from living, BD, and donation after cardiac death in a pig model (n=6 per donor type) were evaluated systematically. BD was induced under general anesthesia by inflating a balloon in the epidural space. Ten hours after confirmation, organs were retrieved. Cardiac arrest was induced by 9V direct current. After 10min of ventricular fibrillation without cardiac output, mechanical and medical reanimation was performed for 30min before organ retrieval. In living donors, organs were explanted immediately. Freeze-clamped biopsies were taken before perfusion with Celsior solution (heart) or University of Wisconsin solution (abdominal organs) in BD and living donors or with Histidine-Tryptophan-Ketoglutaric solution (all organs) in non-heart-beating donors, after perfusion, and after cold ischemia (4h for heart, 6h for liver and pancreas, and 12h for kidney). HEPs (adenosine triphosphate, adenosine diphosphate, adenosine monophosphate, and phosphocreatine), xanthine, and hypoxanthine were measured by high-performance liquid chromatography. Energy charge and adenosine triphosphate-to-adenosine diphosphate ratio were calculated. After ischemia, organs from different donor types showed no difference in energy status. In all organs, a decrease of HEP and an increase in hypoxanthine contents were observed during perfusion and ischemia, irrespective of the donor type. Organs from BD or non-heart-beating donors do not differ from living donor organs in their energy status after average tolerable ischemia. Copyright © 2013 Elsevier Inc. All rights reserved.

Multiparametric evaluation of hindlimb ischemia using time-series indocyanine green fluorescence imaging.

PubMed

Guang, Huizhi; Cai, Chuangjian; Zuo, Simin; Cai, Wenjuan; Zhang, Jiulou; Luo, Jianwen

2017-03-01

Peripheral arterial disease (PAD) can further cause lower limb ischemia. Quantitative evaluation of the vascular perfusion in the ischemic limb contributes to diagnosis of PAD and preclinical development of new drug. In vivo time-series indocyanine green (ICG) fluorescence imaging can noninvasively monitor blood flow and has a deep tissue penetration. The perfusion rate estimated from the time-series ICG images is not enough for the evaluation of hindlimb ischemia. The information relevant to the vascular density is also important, because angiogenesis is an essential mechanism for post-ischemic recovery. In this paper, a multiparametric evaluation method is proposed for simultaneous estimation of multiple vascular perfusion parameters, including not only the perfusion rate but also the vascular perfusion density and the time-varying ICG concentration in veins. The target method is based on a mathematical model of ICG pharmacokinetics in the mouse hindlimb. The regression analysis performed on the time-series ICG images obtained from a dynamic reflectance fluorescence imaging system. The results demonstrate that the estimated multiple parameters are effective to quantitatively evaluate the vascular perfusion and distinguish hypo-perfused tissues from well-perfused tissues in the mouse hindlimb. The proposed multiparametric evaluation method could be useful for PAD diagnosis. The estimated perfusion rate and vascular perfusion density maps (left) and the time-varying ICG concentration in veins of the ankle region (right) of the normal and ischemic hindlimbs. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Role of shear stress in nitric oxide-dependent modulation of renal angiotensin II vasoconstriction.

PubMed

Endlich, K; Muller, C; Barthelmebs, M; Helwig, J J

1999-08-01

1. Renal vasoconstriction in response to angiotensin II (ANGII) is known to be modulated by nitric oxide (NO). Since shear stress stimulates the release of a variety of vasoactive compounds from endothelial cells, we studied the impact of shear stress on the haemodynamic effect of ANGII in isolated perfused kidneys of rats under control conditions and during NO synthase inhibition with L-NAME (100 microM). 2. Kidneys were perfused in the presence of cyclo-oxygenase inhibitor (10 microM indomethacin) with Tyrode's solution of relative viscosity zeta=1 (low viscosity perfusate, LVP) or, in order to augment shear stress, with Tyrode's solution containing 7% Ficoll 70 of relative viscosity zeta=2 (high viscosity perfusate, HVP). 3. Vascular conductance was 3.5+/-0.4 fold larger in HVP as compared with LVP kidneys, associated with an augmentation of overall wall shear stress by 37+/-5%. During NO inhibition, vascular conductance was only 2.5+/-0.2 fold elevated in HVP vs LVP kidneys, demonstrating shear stress-induced vasodilatation by NO and non-NO/non-prostanoid compound(s). 4. ANGII (10 - 100 pM) constricted the vasculature in LVP kidneys, but was without effect in HVP kidneys. During NO inhibition, in contrast, ANGII vasoconstriction was potentiated in HVP as compared with LVP kidneys. 5. The potentiation of ANGII vasoconstriction during NO inhibition has been shown to be mediated by endothelium-derived P450 metabolites and to be sensitive to AT2 receptor blockade in our earlier studies. Accordingly, in HVP kidneys, increasing concentrations of the AT2 receptor antagonist PD123319 (5 and 500 nM) gradually abolished the potentiation of ANGII vasoconstriction during NO inhibition, but did not affect vasoconstriction in response to ANGII in LVP kidneys. 6. Our results demonstrate, that augmentation of shear stress by increasing perfusate viscosity induces vasodilatation in the rat kidney, which is partially mediated by NO. Elevated levels of shear stress attenuate renal ANGII vasoconstriction through enhanced NO production and are required for AT2 sensitive potentiation during NO inhibition.

Role of shear stress in nitric oxide-dependent modulation of renal angiotensin II vasoconstriction

PubMed Central

Endlich, Karlhans; Muller, Catherine; Barthelmebs, Mariette; Helwig, Jean-Jacques

1999-01-01

Renal vasoconstriction in response to angiotensin II (ANGII) is known to be modulated by nitric oxide (NO). Since shear stress stimulates the release of a variety of vasoactive compounds from endothelial cells, we studied the impact of shear stress on the haemodynamic effect of ANGII in isolated perfused kidneys of rats under control conditions and during NO synthase inhibition with L-NAME (100 μM).Kidneys were perfused in the presence of cyclo-oxygenase inhibitor (10 μM indomethacin) with Tyrode's solution of relative viscosity ζ=1 (low viscosity perfusate, LVP) or, in order to augment shear stress, with Tyrode's solution containing 7% Ficoll 70 of relative viscosity ζ=2 (high viscosity perfusate, HVP).Vascular conductance was 3.5±0.4 fold larger in HVP as compared with LVP kidneys, associated with an augmentation of overall wall shear stress by 37±5%. During NO inhibition, vascular conductance was only 2.5±0.2 fold elevated in HVP vs LVP kidneys, demonstrating shear stress-induced vasodilatation by NO and non-NO/non-prostanoid compound(s).ANGII (10–100 pM) constricted the vasculature in LVP kidneys, but was without effect in HVP kidneys. During NO inhibition, in contrast, ANGII vasoconstriction was potentiated in HVP as compared with LVP kidneys.The potentiation of ANGII vasoconstriction during NO inhibition has been shown to be mediated by endothelium-derived P450 metabolites and to be sensitive to AT2 receptor blockade in our earlier studies. Accordingly, in HVP kidneys, increasing concentrations of the AT2 receptor antagonist PD123319 (5 and 500 nM) gradually abolished the potentiation of ANGII vasoconstriction during NO inhibition, but did not affect vasoconstriction in response to ANGII in LVP kidneys.Our results demonstrate, that augmentation of shear stress by increasing perfusate viscosity induces vasodilatation in the rat kidney, which is partially mediated by NO. Elevated levels of shear stress attenuate renal ANGII vasoconstriction through enhanced NO production and are required for AT2 sensitive potentiation during NO inhibition. PMID:10482926

Analysis of the effects on body temperature of intracerebroventricular injection in anaesthetized dogs of gamma-aminobutyric acid

PubMed Central

Dhumal, V.R.; Gulati, O.D.; Raghunath, P.R.; Sivaramakrishna, N.

1974-01-01

1 The cerebral ventricles of dogs under intravenous pentobarbitone sodium anaesthesia, were perfused with artificial cerebro-spinal fluid (CSF) at a rate of 0.4-0.5 ml/min from the ventricular to the aqueductal cannulae. The effluent was collected from the aqueductal cannula in 20 min samples. The animals' temperatures were recorded from the rectum. 2 γ-Aminobutyric acid (GABA) 0.1-5 mg when injected into the ventricles produced variable temperature effects. Doses of 0.1 and 0.5 mg always produced hyperthermia and 1 and 5 mg doses sometimes produced hyperthermia and sometimes hypothermia. 3 Intraventricular perfusion with 2-bromolysergic acid diethylamide (BOL) and hyoscine did not block hyperthermia. Tests on the rat isolated stomach strip or the guinea-pig isolated superfused ileum for the possible release, respectively, of 5-hydroxytryptamine or acetylcholine by GABA were negative. 4 When tested for the presence of prostaglandin E(PGE)-like substances on the isolated rat stomach strip, both the control effluent and the GABA effluent showed activity, the latter being much more potent. There was a temporal correlation between this effect and hyperthermia. Intraventricularly administered sodium salicylate converted the GABA-induced hyperthermia to hypothermia and blocked the release of PGE-like substances. 5 Hypothermia induced by GABA alone or in the presence of sodium salicylate was associated with the release of noradrenaline into the effluent. 6 Intraventricular administration of GABA in reserpinized dogs produced hyperthermia and not hypothermia. Similar results were obtained with phentolamine perfusion in normal dogs. 7 Perfusion with calcium-free solution blocked both the noradrenaline-releasing and hypothermic actions of GABA. 8 It is concluded that hyperthermia associated with intraventricular injections of GABA is due to the release of PGE-like substance and hypothermia is due to the release of noradrenaline. PMID:4155652

Finite volume analysis of temperature effects induced by active MRI implants: 2. Defects on active MRI implants causing hot spots.

PubMed

Busch, Martin H J; Vollmann, Wolfgang; Grönemeyer, Dietrich H W

2006-05-26

Active magnetic resonance imaging implants, for example stents, stent grafts or vena cava filters, are constructed as wireless inductively coupled transmit and receive coils. They are built as a resonator tuned to the Larmor frequency of a magnetic resonance system. The resonator can be added to or incorporated within the implant. This technology can counteract the shielding caused by eddy currents inside the metallic implant structure. This may allow getting diagnostic information of the implant lumen (in stent stenosis or thrombosis for example). The electro magnetic rf-pulses during magnetic resonance imaging induce a current in the circuit path of the resonator. A by material fatigue provoked partial rupture of the circuit path or a broken wire with touching surfaces can set up a relatively high resistance on a very short distance, which may behave as a point-like power source, a hot spot, inside the body part the resonator is implanted to. This local power loss inside a small volume can reach (1/4) of the total power loss of the intact resonating circuit, which itself is proportional to the product of the resonator volume and the quality factor and depends as well from the orientation of the resonator with respect to the main magnetic field and the imaging sequence the resonator is exposed to. First an analytical solution of a hot spot for thermal equilibrium is described. This analytical solution with a definite hot spot power loss represents the worst case scenario for thermal equilibrium inside a homogeneous medium without cooling effects. Starting with this worst case assumptions additional conditions are considered in a numerical simulation, which are more realistic and may make the results less critical. The analytical solution as well as the numerical simulations use the experimental experience of the maximum hot spot power loss of implanted resonators with a definite volume during magnetic resonance imaging investigations. The finite volume analysis calculates the time developing temperature maps for the model of a broken linear metallic wire embedded in tissue. Half of the total hot spot power loss is assumed to diffuse into both wire parts at the location of a defect. The energy is distributed from there by heat conduction. Additionally the effect of blood perfusion and blood flow is respected in some simulations because the simultaneous appearance of all worst case conditions, especially the absence of blood perfusion and blood flow near the hot spot, is very unlikely for vessel implants. The analytical solution as worst case scenario as well as the finite volume analysis for near worst case situations show not negligible volumes with critical temperature increases for part of the modeled hot spot situations. MR investigations with a high rf-pulse density lasting below a minute can establish volumes of several cubic millimeters with temperature increases high enough to start cell destruction. Longer exposure times can involve volumes larger than 100 mm3. Even temperature increases in the range of thermal ablation are reached for substantial volumes. MR sequence exposure time and hot spot power loss are the primary factors influencing the volume with critical temperature increases. Wire radius, wire material as well as the physiological parameters blood perfusion and blood flow inside larger vessels reduce the volume with critical temperature increases, but do not exclude a volume with critical tissue heating for resonators with a large product of resonator volume and quality factor. The worst case scenario assumes thermal equilibrium for a hot spot embedded in homogeneous tissue without any cooling due to blood perfusion or flow. The finite volume analysis can calculate the results for near and not close to worst case conditions. For both cases a substantial volume can reach a critical temperature increase in a short time. The analytical solution, as absolute worst case, points out that resonators with a small product of inductance volume and quality factor (Q V(ind) < 2 cm3) are definitely save. Stents for coronary vessels or resonators used as tracking devices for interventional procedures therefore have no risk of high temperature increases. The finite volume analysis shows for sure that also conditions not close to the worst case reach physiologically critical temperature increases for implants with a large product of inductance volume and quality factor (Q V(ind) > 10 cm3). Such resonators exclude patients from exactly the MRI investigation these devices are made for.

Finite volume analysis of temperature effects induced by active MRI implants: 2. Defects on active MRI implants causing hot spots

PubMed Central

Busch, Martin HJ; Vollmann, Wolfgang; Grönemeyer, Dietrich HW

2006-01-01

Background Active magnetic resonance imaging implants, for example stents, stent grafts or vena cava filters, are constructed as wireless inductively coupled transmit and receive coils. They are built as a resonator tuned to the Larmor frequency of a magnetic resonance system. The resonator can be added to or incorporated within the implant. This technology can counteract the shielding caused by eddy currents inside the metallic implant structure. This may allow getting diagnostic information of the implant lumen (in stent stenosis or thrombosis for example). The electro magnetic rf-pulses during magnetic resonance imaging induce a current in the circuit path of the resonator. A by material fatigue provoked partial rupture of the circuit path or a broken wire with touching surfaces can set up a relatively high resistance on a very short distance, which may behave as a point-like power source, a hot spot, inside the body part the resonator is implanted to. This local power loss inside a small volume can reach ¼ of the total power loss of the intact resonating circuit, which itself is proportional to the product of the resonator volume and the quality factor and depends as well from the orientation of the resonator with respect to the main magnetic field and the imaging sequence the resonator is exposed to. Methods First an analytical solution of a hot spot for thermal equilibrium is described. This analytical solution with a definite hot spot power loss represents the worst case scenario for thermal equilibrium inside a homogeneous medium without cooling effects. Starting with this worst case assumptions additional conditions are considered in a numerical simulation, which are more realistic and may make the results less critical. The analytical solution as well as the numerical simulations use the experimental experience of the maximum hot spot power loss of implanted resonators with a definite volume during magnetic resonance imaging investigations. The finite volume analysis calculates the time developing temperature maps for the model of a broken linear metallic wire embedded in tissue. Half of the total hot spot power loss is assumed to diffuse into both wire parts at the location of a defect. The energy is distributed from there by heat conduction. Additionally the effect of blood perfusion and blood flow is respected in some simulations because the simultaneous appearance of all worst case conditions, especially the absence of blood perfusion and blood flow near the hot spot, is very unlikely for vessel implants. Results The analytical solution as worst case scenario as well as the finite volume analysis for near worst case situations show not negligible volumes with critical temperature increases for part of the modeled hot spot situations. MR investigations with a high rf-pulse density lasting below a minute can establish volumes of several cubic millimeters with temperature increases high enough to start cell destruction. Longer exposure times can involve volumes larger than 100 mm3. Even temperature increases in the range of thermal ablation are reached for substantial volumes. MR sequence exposure time and hot spot power loss are the primary factors influencing the volume with critical temperature increases. Wire radius, wire material as well as the physiological parameters blood perfusion and blood flow inside larger vessels reduce the volume with critical temperature increases, but do not exclude a volume with critical tissue heating for resonators with a large product of resonator volume and quality factor. Conclusion The worst case scenario assumes thermal equilibrium for a hot spot embedded in homogeneous tissue without any cooling due to blood perfusion or flow. The finite volume analysis can calculate the results for near and not close to worst case conditions. For both cases a substantial volume can reach a critical temperature increase in a short time. The analytical solution, as absolute worst case, points out that resonators with a small product of inductance volume and quality factor (Q Vind < 2 cm3) are definitely save. Stents for coronary vessels or resonators used as tracking devices for interventional procedures therefore have no risk of high temperature increases. The finite volume analysis shows for sure that also conditions not close to the worst case reach physiologically critical temperature increases for implants with a large product of inductance volume and quality factor (Q Vind > 10 cm3). Such resonators exclude patients from exactly the MRI investigation these devices are made for. PMID:16729878

A kinetic approach to the study of absorption of solutes by isolated perfused small intestine

PubMed Central

Fisher, R. B.; Gardner, M. L. G.

1974-01-01

1. A new technique has been developed for making serial measurements of water and solute absorption from the lumen of isolated small intestine. 2. The isolated intestine is perfused in a single pass with a segmented flow of slugs of liquid separated by bubbles of oxygen-carbon dioxide mixture. Simultaneous collections are made of effluent from the lumen and of the fluid which is transported across the mucosa. This latter fluid appears to be a fair sample of the tissue fluid. 3. Conditions in the lumen can be changed within less than 5 min. The effects of two or more treatments applied to the same segment of intestine can be determined and the time course of a change in luminal conditions. 4. The rate of appearance of solutes on the serosal side depends on the rate of water absorption, and changes exponentially towards a steady state. The rate constant is a function of tissue fluid volume. 5. In the steady state the concentration of glucose in the tissue fluid is 71 mM when the luminal concentration is 28 mM, and is 45 mM when the luminal concentration is 8·3 mM. 6. For solutes such as glucose for which reflux from tissue fluid to lumen is small relative to flux from lumen to tissue fluid, the time of attainment of a steady state in secretion is usually 50-60 min. 7. For solutes such as sodium for which the reflux is relatively high, the steady state may be reached in 15-20 min. 8. The Km for glucose absorption (14-19 mM) is much lower than is found with unsegmented flow perfusion. 9. These findings emphasize problems in interpreting results from other types of intestinal preparation. 10. The rate of glucose absorption from the lumen falls only gradually when the luminal sodium concentration is reduced abruptly. In contrast the rate of glucose absorption falls suddenly when the luminal glucose concentration is reduced abruptly. This suggests that glucose absorption is not directly dependent on luminal sodium ions. ImagesPlate 1 PMID:4422346

Histogram Analysis of CT Perfusion of Hepatocellular Carcinoma for Predicting Response to Transarterial Radioembolization: Value of Tumor Heterogeneity Assessment

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

Reiner, Caecilia S., E-mail: caecilia.reiner@usz.ch; Gordic, Sonja; Puippe, Gilbert

2016-03-15

PurposeTo evaluate in patients with hepatocellular carcinoma (HCC), whether assessment of tumor heterogeneity by histogram analysis of computed tomography (CT) perfusion helps predicting response to transarterial radioembolization (TARE).Materials and MethodsSixteen patients (15 male; mean age 65 years; age range 47–80 years) with HCC underwent CT liver perfusion for treatment planning prior to TARE with Yttrium-90 microspheres. Arterial perfusion (AP) derived from CT perfusion was measured in the entire tumor volume, and heterogeneity was analyzed voxel-wise by histogram analysis. Response to TARE was evaluated on follow-up imaging (median follow-up, 129 days) based on modified Response Evaluation Criteria in Solid Tumors (mRECIST). Results of histogrammore » analysis and mean AP values of the tumor were compared between responders and non-responders. Receiver operating characteristics were calculated to determine the parameters’ ability to discriminate responders from non-responders.ResultsAccording to mRECIST, 8 patients (50 %) were responders and 8 (50 %) non-responders. Comparing responders and non-responders, the 50th and 75th percentile of AP derived from histogram analysis was significantly different [AP 43.8/54.3 vs. 27.6/34.3 mL min{sup −1} 100 mL{sup −1}); p < 0.05], while the mean AP of HCCs (43.5 vs. 27.9 mL min{sup −1} 100 mL{sup −1}; p > 0.05) was not. Further heterogeneity parameters from histogram analysis (skewness, coefficient of variation, and 25th percentile) did not differ between responders and non-responders (p > 0.05). If the cut-off for the 75th percentile was set to an AP of 37.5 mL min{sup −1} 100 mL{sup −1}, therapy response could be predicted with a sensitivity of 88 % (7/8) and specificity of 75 % (6/8).ConclusionVoxel-wise histogram analysis of pretreatment CT perfusion indicating tumor heterogeneity of HCC improves the pretreatment prediction of response to TARE.« less

Comparing cerebral perfusion in Alzheimer's disease and Parkinson's disease dementia: an ASL-MRI study.

PubMed

Le Heron, Campbell J; Wright, Sarah L; Melzer, Tracy R; Myall, Daniel J; MacAskill, Michael R; Livingston, Leslie; Keenan, Ross J; Watts, Richard; Dalrymple-Alford, John C; Anderson, Tim J

2014-06-01

Emerging evidence suggests that Alzheimer's disease (AD) and Parkinson's disease dementia (PDD) share neurodegenerative mechanisms. We sought to directly compare cerebral perfusion in these two conditions using arterial spin labeling magnetic resonance imaging (ASL-MRI). In total, 17 AD, 20 PDD, and 37 matched healthy controls completed ASL and structural MRI, and comprehensive neuropsychological testing. Alzheimer's disease and PDD perfusion was analyzed by whole-brain voxel-based analysis (to assess absolute blood flow), a priori specified region of interest analysis, and principal component analysis (to generate a network differentiating the two groups). Corrections were made for cerebral atrophy, age, sex, education, and MRI scanner software version. Analysis of absolute blood flow showed no significant differences between AD and PDD. Comparing each group with controls revealed an overlapping, posterior pattern of hypoperfusion, including posterior cingulate gyrus, precuneus, and occipital regions. The perfusion network that differentiated AD and PDD groups identified relative differences in medial temporal lobes (AD

Three-dimensional MRI perfusion maps: a step beyond volumetric analysis in mental disorders

PubMed Central

Fabene, Paolo F; Farace, Paolo; Brambilla, Paolo; Andreone, Nicola; Cerini, Roberto; Pelizza, Luisa; Versace, Amelia; Rambaldelli, Gianluca; Birbaumer, Niels; Tansella, Michele; Sbarbati, Andrea

2007-01-01

A new type of magnetic resonance imaging analysis, based on fusion of three-dimensional reconstructions of time-to-peak parametric maps and high-resolution T1-weighted images, is proposed in order to evaluate the perfusion of selected volumes of interest. Because in recent years a wealth of data have suggested the crucial involvement of vascular alterations in mental diseases, we tested our new method on a restricted sample of schizophrenic patients and matched healthy controls. The perfusion of the whole brain was compared with that of the caudate nucleus by means of intrasubject analysis. As expected, owing to the encephalic vascular pattern, a significantly lower time-to-peak was observed in the caudate nucleus than in the whole brain in all healthy controls, indicating that the suggested method has enough sensitivity to detect subtle perfusion changes even in small volumes of interest. Interestingly, a less uniform pattern was observed in the schizophrenic patients. The latter finding needs to be replicated in an adequate number of subjects. In summary, the three-dimensional analysis method we propose has been shown to be a feasible tool for revealing subtle vascular changes both in normal subjects and in pathological conditions. PMID:17229290

Perfusion cell culture decreases process and product heterogeneity in a head-to-head comparison with fed-batch.

PubMed

Walther, Jason; Lu, Jiuyi; Hollenbach, Myles; Yu, Marcella; Hwang, Chris; McLarty, Jean; Brower, Kevin

2018-05-30

In this study, we compared the impacts of fed-batch and perfusion platforms on process and product attributes for IgG1- and IgG4-producing cell lines. A "plug-and-play" approach was applied to both platforms at bench scale, using commercially available basal and feed media, a standard feed strategy for fed-batch, and ATF filtration for perfusion. Product concentration in fed-batch was 2.5 times greater than perfusion, while average productivity in perfusion was 7.5 times greater than fed-batch. PCA revealed more variability in the cell environment and metabolism during the fed-batch run. LDH measurements showed that exposure of product to cell lysate was 7-10 times greater in fed-batch. Product analysis shows larger abundances of neutral species in perfusion, likely due to decreased bioreactor residence times and extracellular exposure. The IgG1 perfusion product also had higher purity and lower half-antibody. Glycosylation was similar across both culture modes. The first perfusion harvest slice for both product types showed different glycosylation than subsequent harvests, suggesting that product quality lags behind metabolism. In conclusion, process and product data indicate that intra-lot heterogeneity is decreased in perfusion cultures. Additional data and discussion is required to understand the developmental, clinical and commercial implications, and in what situations increased uniformity would be beneficial. This article is protected by copyright. All rights reserved.

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 American Association for the Study of Liver Diseases.

Sieving of electrolytes at capillary wall of cat skeletal muscle by osmotic water flow.

PubMed

Watson, P D

1993-12-01

To test the hypothesis that a significant proportion of transcapillary water flow occurs through solute-restricting channels, we investigated the effects of transcapillary water movement on plasma electrolytes in isolated perfused cat skeletal muscle. The lower hindlimbs of anesthetized cats were perfused with a plasma-albumin solution and were weighed to determine transcapillary water movement. Osmolality was increased 60-70 mosmol/kgH2O with sucrose, creating water fluxes of 8-10 ml.min-1.100 g-1, and the changes in the venous concentrations of sodium, potassium, and chloride were determined. The ion concentrations were all reduced by 6-7% with no significant difference between them. The amount of reduction was quantitatively explained by the flow of ion-free water from the interstitial space into plasma and the diffusion of electrolyte in the same direction. These findings support the hypothesis that important water-only transcapillary channels exist in mammalian skeletal muscle. The observations may also explain some of the electrolyte changes seen in intense exercise.

SUCCESSFUL TREATMENT OF DIGITAL OSTEITIS BY INTRAVENOUS REGIONAL PERFUSION OF CEFTIOFUR IN AN AFRICAN ELEPHANT (LOXODONTA AFRICANA).

PubMed

Dutton, Christopher J; Delnatte, Pauline G; Hollamby, Simon R; Crawshaw, Graham J

2017-06-01

A 41-yr-old African elephant ( Loxodonta africana ) presented with a swollen third digit of the left forelimb and a 2-cm hole in the pad. Corrective trimming, topical treatments, and an oral antibiotic resulted in apparent resolution; however, it reoccurred after 4 mo. Radiographs suggested bone lysis in the third phalanx, with the primary differential diagnosis being septic osteitis. Flushing with metronidazole solution and intravenous regional perfusion (IVRP) of the foot were commenced. A tourniquet was applied just above the carpus, an interdigital vein was identified by ultrasound, and into this vein 2 g (20 ml) of ceftiofur sodium solution, followed by 60 ml of heparinized saline, was administered. The foot was kept raised for 25 min and then the tourniquet was removed. IVRP was repeated every other day for 70 treatments over 6 mo. Healing occurred, which was confirmed radiographically. IVRP offers an excellent treatment modality in a well-trained elephant.

Modification of caffeine-induced injury in Ca2+-free perfused rat hearts. Relationship to the calcium paradox.

PubMed Central

Vander Heide, R. S.; Altschuld, R. A.; Lamka, K. G.; Ganote, C. E.

1986-01-01

The pathogenesis of the calcium paradox has not been established. In calcium-free perfused hearts, caffeine, which releases calcium from the sarcoplasmic reticulum, causes severe myocardial injury, with creatine kinase (CK) release and contraction band necrosis similar in many respects to the calcium paradox. It has been postulated that contracture, initiated by a small rise in intracellular calcium, may cause sarcolemmal injury in both the calcium paradox and caffeine-induced myocardial injury. The present study was initiated to determine whether interventions which modulate caffeine-induced contracture will also correspondingly alter cellular injury. The effects of caffeine dose, procaine, extended calcium-free perfusion, elevated potassium, temperature, and increasing intracellular sodium on caffeine-induced contracture were examined in Langendorff-perfused adult rat hearts. Caffeine-induced contracture at 22 C increased over a dose range of 5-40 mM caffeine. Procaine, which inhibits caffeine-induced calcium release at doses between 5 and 20 mM, progressively reduced contracture caused by addition of 20 mM caffeine at 22 C. Hearts perfused with calcium-free solution containing 16 mM K+ showed a reduction in caffeine-induced contracture. Extended calcium-free perfusion (20 minutes) at temperatures from 18 to 37 C resulted in a progressive reduction of caffeine-induced contracture. Each of these interventions was also found to inhibit caffeine-induced injury at 37 C. Low temperature was found to have complex effects. Hypothermia enhanced caffeine contractures but also protected hearts from cell separations and CK release. Increasing intracellular sodium was found to enhance caffeine-induced contracture at 37 C. There was a direct correlation between measured intracellular sodium levels and the magnitude and duration of caffeine-induced contracture. These results demonstrate a direct correlation between the magnitude of contracture and myocardial injury in calcium-free hearts. It is proposed that contracture is the primary mediator of sarcolemmal membrane injury in hearts with intercalated disks weakened by prior calcium-free perfusion. Images Figure 11 PMID:3706496

Computational analysis of blood clot dissolution using a vibrating catheter tip.

PubMed

Lee, Jeong Hyun; Oh, Jin Sun; Yoon, Bye Ri; Choi, Seung Hong; Rhee, Kyehan; Jho, Jae Young; Han, Moon Hee

2012-04-01

We developed a novel concept of endovascular thrombolysis that employs a vibrating electroactive polymer actuator. In order to predict the efficacy of thrombolysis using the developed vibrating actuator, enzyme (plasminogen activator) perfusion into a clot was analyzed by solving flow fields and species transport equations considering the fluid structure interaction. In vitro thrombolysis experiments were also performed. Computational results showed that plasminogen activator perfusion into a clot was enhanced by actuator vibration at frequencies of 1 and 5 Hz. Plasminogen activator perfusion was affected by the actuator oscillation frequencies and amplitudes that were determined by electromechanical characteristics of a polymer actuator. Computed plasminogen activator perfused volumes were compared with experimentally measured dissolved clot volumes. The computed plasminogen activator perfusion volumes with threshold concentrations of 16% of the initial plasminogen activator concentration agreed well with the in vitro experimental data. This study showed the effectiveness of actuator oscillation on thrombolysis and the validity of the computational plasminogen activator perfusion model for predicting thrombolysis in complex flow fields induced by an oscillating actuator.

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 maximum percentage deviation is about 5%. Then the SI-method was used in comparison to a delayed enhanced method to qualitatively and quantitatively assess perfusion deficits in an ischemia-reperfusion (IR) mouse model. The infarcted region of the perfusion map is comparable to the hyper intense region of the delayed enhanced image of the IR mouse. The SI method also used to record a chronological comparison of perfusion on delta sarcoglycan null (DSG) mice. Perfusion of DSG and wild-type (WT) mice at ages of 12 weeks and 32 weeks were compared and percentage change of perfusion was estimated. The result shows that in DSG mice perfusion changes considerably. Finally, the SI method was implemented on a 3 Tesla Philip scanner by modifying to data acquisition method. The perfusion obtained in this is consistent with literature values but further adjustment of pulse sequence and modification of numerical solution is needed. The most important benefit of the SI method is that it reduces scan time 30%--40% and lessens motion artifacts of images compared to the T1 method. This study demonstrates that the signal intensity-based ASL method is a robust alternative to the conventional T1-method.

Application of perfusion culture system improves in vitro and in vivo osteogenesis of bone marrow-derived osteoblastic cells in porous ceramic materials.

PubMed

Wang, Yichao; Uemura, Toshimasa; Dong, Jian; Kojima, Hiroko; Tanaka, Junzo; Tateishi, Tetsuya

2003-12-01

Composites of bone marrow-derived osteoblasts (BMOs) and porous ceramics have been widely used as a bone graft model for bone tissue engineering. Perfusion culture has potential utility for many cell types in three-dimensional (3D) culture. Our hypothesis was that perfusion of medium would increase the cell viability and biosynthetic activity of BMOs in porous ceramic materials, which would be revealed by increased levels of alkaline phosphate (ALP) activity and osteocalcin (OCN) and enhanced bone formation in vivo. For testing in vitro, BMO/beta-tricalcium phosphate composites were cultured in a perfusion container (Minucells and Minutissue, Bad Abbach, Germany) with fresh medium delivered at a rate of 2 mL/h by a peristaltic pump. The ALP activity and OCN content of composites were measured at the end of 1, 2, 3, and 4 weeks of subculture. For testing in vivo, after subculturing for 2 weeks, the composites were subcutaneously implanted into syngeneic rats. These implants were harvested 4 or 8 weeks later. The samples then underwent a biochemical analysis of ALP activity and OCN content and were observed by light microscopy. The levels of ALP activity and OCN in the composites were significantly higher in the perfusion group than in the control group (p < 0.01), both in vitro and in vivo. Histomorphometric analysis of the hematoxylin- and eosin-stained sections revealed a higher average ratio of bone to pore in BMO/beta-TCP composites of the perfusion group after implantation: 47.64 +/- 6.16 for the perfusion group and 26.22 +/- 4.84 for control at 4 weeks (n = 6, p < 0.01); 67.97 +/- 3.58 for the perfusion group and 47.39 +/- 4.10 for control at 8 weeks (n = 6, p < 0.05). These results show that the application of a perfusion culture system during the subculture of BMOs in a porous ceramic scaffold is beneficial to their osteogenesis. After differentiation culture in vitro with the perfusion culture system, the activity of the osteoblastic cells and the consequent bone formation in vivo were significantly enhanced. These results suggest that the perfusion culture system is a valuable and convenient tool for applications in tissue engineering, especially in the generation of artificial bone tissue.

Perfusion Scintigraphy and Patient Selection for Lung Volume Reduction Surgery

PubMed Central

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

2010-01-01

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

Perfusion quantification in contrast-enhanced ultrasound (CEUS)--ready for research projects and routine clinical use.

PubMed

Tranquart, F; Mercier, L; Frinking, P; Gaud, E; Arditi, M

2012-07-01

With contrast-enhanced ultrasound (CEUS) now established as a valuable imaging modality for many applications, a more specific demand has recently emerged for quantifying perfusion and using measured parameters as objective indicators for various disease states. However, CEUS perfusion quantification remains challenging and is not well integrated in daily clinical practice. The development of VueBox™ alleviates existing limitations and enables quantification in a standardized way. VueBox™ operates as an off-line software application, after dynamic contrast-enhanced ultrasound (DCE-US) is performed. It enables linearization of DICOM clips, assessment of perfusion using patented curve-fitting models, and generation of parametric images by synthesizing perfusion information at the pixel level using color coding. VueBox™ is compatible with most of the available ultrasound platforms (nonlinear contrast-enabled), has the ability to process both bolus and disruption-replenishment kinetics loops, allows analysis results and their context to be saved, and generates analysis reports automatically. Specific features have been added to VueBox™, such as fully automatic in-plane motion compensation and an easy-to-use clip editor. Processing time has been reduced as a result of parallel programming optimized for multi-core processors. A long list of perfusion parameters is available for each of the two administration modes to address all possible demands currently reported in the literature for diagnosis or treatment monitoring. In conclusion, VueBox™ is a valid and robust quantification tool to be used for standardizing perfusion quantification and to improve the reproducibility of results across centers. © Georg Thieme Verlag KG Stuttgart · New York.

[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.

Pressure- and flow-controlled media perfusion differently modify vascular mechanics in lung decellularization.

PubMed

da Palma, Renata K; Campillo, Noelia; Uriarte, Juan J; Oliveira, Luis V F; Navajas, Daniel; Farré, Ramon

2015-09-01

Organ biofabrication is a potential future alternative for obtaining viable organs for transplantation. Achieving intact scaffolds to be recellularized is a key step in lung bioengineering. Perfusion of decellularizing media through the pulmonary artery has shown to be effective. How vascular perfusion pressure and flow vary throughout lung decellularization, which is not well known, is important for optimizing the process (minimizing time) while ensuring scaffold integrity (no barotrauma). This work was aimed at characterizing the pressure/flow relationship at the pulmonary vasculature and at how effective vascular resistance depends on pressure- and flow-controlled variables when applying different methods of media perfusion for lung decellularization. Lungs from 43 healthy mice (C57BL/6; 7-8 weeks old) were investigated. After excision and tracheal cannulation, lungs were inflated at 10 cmH2O airway pressure and subjected to conventional decellularization with a solution of 1% sodium dodecyl sulfate (SDS). Pressure (PPA) and flow (V'PA) at the pulmonary artery were continuously measured. Decellularization media was perfused through the pulmonary artery: (a) at constant PPA=20 cmH2O or (b) at constant V'PA=0.5 and 0.2 ml/min. Effective vascular resistance was computed as Rv=PPA/V'PA. Rv (in cmH2O/(ml/min)); mean±SE) considerably varied throughout lung decellularization, particularly for pressure-controlled perfusion (from 29.1±3.0 in baseline to a maximum of 664.1±164.3 (p<0.05), as compared with flow-controlled perfusion (from 49.9±3.3 and 79.5±5.1 in baseline to a maximum of 114.4±13.9 and 211.7±70.5 (p<0.05, both), for V'PA of 0.5 and 0.2 ml/min respectively. Most of the media infused to the pulmonary artery throughout decellularization circulated to the airways compartment across the alveolar-capillary membrane. This study shows that monitoring perfusion mechanics throughout decellularization provides information relevant for optimizing the process time while ensuring that vascular pressure is kept within a safety range to preserve the organ scaffold integrity. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

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

PubMed Central

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

2014-01-01

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

In vitro performance of a perfusion and oxygenation optical sensor using a unique liver phantom

NASA Astrophysics Data System (ADS)

Akl, Tony J.; King, Travis J.; Long, Ruiqi; Ericson, M. N.; Wilson, Mark A.; McShane, Michael J.; Coté, Gerard L.

2012-03-01

Between the years 1999 and 2008, on average 2,052 people died per year on the waiting list for liver transplants. Monitoring perfusion and oxygenation in transplanted organs in the 7 to 14 days period post-transplant can enhance graft and patient survival rates, and resultantly increase the availability of organs. In this work, we present in vitro results using a unique liver phantom that support the ability of our sensor to detect perfusion changes in the portal vein at low levels (50 mL/min . 4.5% of normal level). Our sensor measures diffuse reflection from three wavelengths (735, 805 and 940 nm) around the hemoglobin isobestic point (805 nm) to determine perfusion and oxygenation separately. To assess the sensitivity of our sensor to flow changes in the low range, we used two peristaltic pumps to pump a dye solution mimicking the optical properties of oxygenated blood, at various rates, through a PDMS based phantom mimicking the optical properties of liver tissue. The collected pulsatile signal increased by 120% (2.2X) for every 100 mL/min flow rise for all three wavelengths in the range 50 to 500 mL/min. In addition, we used different dye mixtures to mimic oxygenation changes at constant perfusion/flow levels. The optical properties of the dye mixtures mimic oxygen saturations ranging between 0 and 100%. The sensor was shown to be sensitive to changes in oxygen saturations above 50%.

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.

Eliminating the blood-flow confounding effect in intravoxel incoherent motion (IVIM) using the non-negative least square analysis in liver.

PubMed

Gambarota, Giulio; Hitti, Eric; Leporq, Benjamin; Saint-Jalmes, Hervé; Beuf, Olivier

2017-01-01

Tissue perfusion measurements using intravoxel incoherent motion (IVIM) diffusion-MRI are of interest for investigations of liver pathologies. A confounding factor in the perfusion quantification is the partial volume between liver tissue and large blood vessels. The aim of this study was to assess and correct for this partial volume effect in the estimation of the perfusion fraction. MRI experiments were performed at 3 Tesla with a diffusion-MRI sequence at 12 b-values. Diffusion signal decays in liver were analyzed using the non-negative least square (NNLS) method and the biexponential fitting approach. In some voxels, the NNLS analysis yielded a very fast-decaying component that was assigned to partial volume with the blood flowing in large vessels. Partial volume correction was performed by biexponential curve fitting, where the first data point (b = 0 s/mm 2 ) was eliminated in voxels with a very fast-decaying component. Biexponential fitting with partial volume correction yielded parametric maps with perfusion fraction values smaller than biexponential fitting without partial volume correction. The results of the current study indicate that the NNLS analysis in combination with biexponential curve fitting allows to correct for partial volume effects originating from blood flow in IVIM perfusion fraction measurements. Magn Reson Med 77:310-317, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Pulmonary preservation studies: effects on endothelial function and pulmonary adenine nucleotides.

PubMed

Paik, Hyo Chae; Hoffmann, Steven C; Egan, Thomas M

2003-02-27

Lung transplantation is an effective therapy plagued by a high incidence of early graft dysfunction, in part because of reperfusion injury. The optimal preservation solution for lung transplantation is unknown. We performed experiments using an isolated perfused rat lung model to test the effect of lung preservation with three solutions commonly used in clinical practice. Lungs were retrieved from Sprague-Dawley rats and flushed with one of three solutions: modified Euro-Collins (MEC), University of Wisconsin (UW), or low potassium dextran and glucose (LPDG), then stored cold for varying periods before reperfusion with Earle's balanced salt solution using the isolated perfused rat lung model. Outcome measures were capillary filtration coefficient (Kfc), wet-to-dry weight ratio, and lung tissue levels of adenine nucleotides and cyclic AMP. All lungs functioned well after 4 hr of storage. By 6 hr, UW-flushed lungs had a lower Kfc than LPDG-flushed lungs. After 8 hr of storage, only UW-flushed lungs had a measurable Kfc. Adenine nucleotide levels were higher in UW-flushed lungs after prolonged storage. Cyclic AMP levels correlated with Kfc in all groups. Early changes in endothelial permeability seemed to be better attenuated in lungs flushed with UW compared with LPDG or MEC; this was associated with higher amounts of adenine nucleotides. MEC-flushed lungs failed earlier than LPDG-flushed or UW-flushed lungs. The content of the solution may be more important for lung preservation than whether the ionic composition is intracellular or extracellular.

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.

Mathematical Model Formulation And Validation Of Water And Solute Transport In Whole Hamster Pancreatic Islets

PubMed Central

Benson, Charles T.; Critser, John K.

2014-01-01

Optimization of cryopreservation protocols for cells and tissues requires accurate models of heat and mass transport. Model selection often depends on the configuration of the tissue. Here, a mathematical and conceptual model of water and solute transport for whole hamster pancreatic islets has been developed and experimentally validated incorporating fundamental biophysical data from previous studies on individual hamster islet cells while retaining whole-islet structural information. It describes coupled transport of water and solutes through the islet by three methods: intracellularly, intercellularly, and in combination. In particular we use domain decomposition techniques to couple a transmembrane flux model with an interstitial mass transfer model. The only significant undetermined variable is the cellular surface area which is in contact with the intercellularly transported solutes, Ais. The model was validated and Ais determined using a 3 × 3 factorial experimental design blocked for experimental day. Whole islet physical experiments were compared with model predictions at three temperatures, three perfusing solutions, and three islet size groups. A mean of 4.4 islets were compared at each of the 27 experimental conditions and found to correlate with a coefficient of determination of 0.87 ± 0.06 (mean ± S.D.). Only the treatment variable of perfusing solution was found to be significant (p < 0.05). We have devised a model that retains much of the intrinsic geometric configuration of the system, and thus fewer laboratory experiments are needed to determine model parameters and thus to develop new optimized cryopreservation protocols. Additionally, extensions to ovarian follicles and other concentric tissue structures may be made. PMID:24950195

Pancreas preservation for pancreas and islet transplantation

PubMed Central

Iwanaga, Yasuhiro; Sutherland, David E.R.; Harmon, James V.; Papas, Klearchos K.

2010-01-01

Purpose of review To summarize advances and limitations in pancreas procurement and preservation for pancreas and islet transplantation, and review advances in islet protection and preservation. Recent findings Pancreases procured after cardiac death, with in-situ regional organ cooling, have been successfully used for islet transplantation. Colloid-free Celsior and histidine-tryptophan-ketoglutarate preservation solutions are comparable to University of Wisconsin solution when used for cold storage before pancreas transplantation. Colloid-free preservation solutions are inferior to University of Wisconsin solution for pancreas preservation prior to islet isolation and transplantation. Clinical reports on pancreas and islet transplants suggest that the two-layer method may not offer significant benefits over cold storage with the University of Wisconsin solution: improved oxygenation may depend on the graft size; benefits in experimental models may not translate to human organs. Improvements in islet yield and quality occurred from pancreases treated with inhibitors of stress-induced apoptosis during procurement, storage, isolation or culture. Pancreas perfusion may be desirable before islet isolation and transplantation and may improve islet yields and quality. Methods for real-time, noninvasive assessment of pancreas quality during preservation have been implemented and objective islet potency assays have been developed and validated. These innovations should contribute to objective evaluation and establishment of improved pancreas preservation and islet isolation strategies. Summary Cold storage may be adequate for preservation before pancreas transplants, but insufficient when pancreases are processed for islets or when expanded donors are used. Supplementation of cold storage solutions with cytoprotective agents and perfusion may improve pancreas and islet transplant outcomes. PMID:18685343

A fast solution switching system with temperature control for single cell measurements

PubMed Central

Koh, Duk-Su; Chen, Liangyi; Ufret-Vincenty, Carmen A.; Jung, Seung-Ryoung

2011-01-01

This article describes a perfusion system for biophysical single cell experiments at the physiological temperature. Our system regulates temperature of test solutions using a small heat exchanger that includes several capillaries. Water circulating inside the heat exchanger warms or cools test solutions flowing inside the capillaries. Temperature-controlled solutions are delivered directly to a single cell(s) through a multibarreled manifold that switches solutions bathing a cell in less than 1 s. This solution exchange is optimal for patch clamp, single-cell microamperometry, and microfluorometry experiments. Using this system, we demonstrate that exocytosis from pancreatic β cells and activation of TRPV1 channels are temperature sensitive. We also discuss how to measure local temperature near a single cell under investigation. PMID:21536068

Hypothermic preservation of corneas in a hyperkalaemic solution (CPTES): I. Short-term storage in the absence of colloid osmotic agents.

PubMed Central

Taylor, M J; Hunt, C J

1989-01-01

Preservation solutions for short-term storage of isolated donor corneas for use in penetrating keratoplasty have all been based on tissue culture medium, on the assumption that media designed to maintain the viability of cells at physiological temperatures will also provide suitable conditions for preservation at reduced temperatures. But for hypothermic preservation of some other tissues and organs, when ionic pumps are inhibited, it is unnecessary to support metabolism, and beneficial control of ion and water distribution between intra- and extracellular compartments is achieved by storage in appropriately formulated 'intracellular-type' solutions. We have therefore designed a solution that will restrict ionic imbalances and minimise endothelial cell swelling in corneas during exposure at reduced temperatures. This potassium-rich solution contains the biological pH buffer TES as an impermeant anion and is designated CPTES (corneal-potassium-TES). The structural and functional integrity of rabbit corneas stored at 0 degrees C in CPTES, without the addition of colloid osmotic agents, is compared with that of corneas stored in glutathione bicarbonate Ringers' solution (GBR), an 'extracellular-type' medium formulated for the maintenance of endothelial integrity during in-vitro perfusion at 34 degrees C. Corneas swelled significantly less during storage in CPTES than in GBR and could be stored for five days before reaching the same degree of hydration as corneas stored for only three days in GBR. Gross structural integrity and endothelial ultrastructure were maintained during storage for three and five days in CPTES. The rate of thinning of corneas stored in CPTES was significantly greater than in comparable groups of corneas stored in GBR. However, the efficient dehydration of corneas stored in CPTES was always preceded during perfusion by a brief period of additional swelling which was shown to be an osmotic response during the elution of the buffer compound TES that had permeated the stroma during storage. The omission of calcium or the addition of adenosine and glutathione to the CPTES preservation medium had no detectable effect on the integrity of the endothelium, but the omission of bicarbonate was beneficial, producing significantly higher rates of stromal thinning during normothermic perfusion. Additional benefits for extending storage by including colloid osmotic agents are described in a companion paper. Images PMID:2818988

Wavelet analysis of the Laser Doppler signal to assess skin perfusion.

PubMed

Bagno, Andrea; Martini, Romeo

2015-01-01

The hemodynamics of skin microcirculation can be clinically assessed by means of Laser Doppler Fluxmetry. Laser Doppler signals show periodic oscillations because of fluctuations of microvascular perfusion (flowmotion), which are sustained by contractions and relaxations of arteriolar walls rhythmically changing vessels diameter (vasomotion). The wavelet analysis applied to Laser Doppler signals displays six characteristic frequency intervals, from 0.005 to 2 Hz. Each interval is assigned to a specific structure of the cardiovascular system: heart, respiration, vascular myocites, sympathetic terminations, and endothelial cells (dependent and independent on nitric oxide). Therefore, mechanisms of skin perfusion can be investigated through wavelet analysis. In the present work, examples of methods and results of wavelet analysis applied to Laser Doppler signals are reported. Laser Doppler signals were acquired in two groups of patients to check possible changes in vascular activities, before and after occlusive reactive hyperaemia, and before and after revascularization.

[Myocardial perfusion scintigraphy - short form of the German guideline].

PubMed

Lindner, O; Burchert, W; Hacker, M; Schaefer, W; Schmidt, M; Schober, O; Schwaiger, M; vom Dahl, J; Zimmermann, R; Schäfers, M

2013-01-01

This guideline is a short summary of the guideline for myocardial perfusion scintigraphy published by the Association of the Scientific Medical Societies in Ger-many (AWMF). The purpose of this guideline is to provide practical assistance for indication and examination procedures as well as image analysis and to present the state-of-the-art of myocardial-perfusion-scintigraphy. After a short introduction on the fundamentals of imaging, precise and detailed information is given on the indications, patient preparation, stress testing, radiopharmaceuticals, examination protocols and techniques, radiation exposure, data reconstruction as well as information on visual and quantitative image analysis and interpretation. In addition possible pitfalls, artefacts and key elements of reporting are described.

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

[5-HT(1A) receptors are involved in the modulation of respiratory rhythmical discharge activity in the medulla oblongata slice preparation of neonatal rats].

PubMed

Qin, Zheng; Wu, Zhong-Hai; Wang, Xiao-Feng

2007-06-25

The present study was carried out to determine the role of 5-HT(1A) receptors in the generation and modulation of basic respiratory rhythm. Neonatal (aged 0-3 d) Sprague-Dawley rats of either sex were used. The medulla oblongata slice was prepared and the surgical procedure was performed in the modified Kreb's solution (MKS) with continuous carbogen (95% O2 and 5% CO2), and ended in 3 min. In cold MKS, a 600-700 microm single transverse slice was cut, which was rostral to the edge of area postrema and retained the hypoglossal nerve roots and some parts of the ventral respiratory group. The preparation was quickly transferred to a recording chamber and continuously perfused with carbogen-saturated MKS at a rate of 4-6 mL/min at 27-29 degrees C. Glass adsorb-electrodes containing Ag-AgCl needle were attached to the ventral roots of the hypoglossal nerve. Respiratory rhythmical discharge activity (RRDA) of the rootlets of hypoglossal nerve was recorded. Ten medulla oblongata slice preparations were divided into two groups. In group I, 5-HT(1A) receptor specific agonist (+/-)-8-hydroxy-2-(di-N-propylamino)tetralin hydrobromide (8-OHDPAT, 20 micromol/L) was added into the perfusion solution for 10 min first, after washing out, the 5-HT(1A) antagonist [4-iodo-N-[2-[4-methoxyphenyl]-1-piperazinyl]ethyl]-N-2-pyridynyl-benzamide hydrochloride] (PMPPI, 10 micromol/L) was applied to the perfusion solution for 10 min. In group II, after application of 8-OHDPAT for 10 min, additional PMPPI was added into the perfusion solution for 10 min. The discharges of the rootlets of hypoglossal nerve were recorded. Signals were amplified and band-pass filtered (100-3.3 kHz). Data were sampled (1-10 kHz) and stored in the computer via BL-420 biological signal processing system. Our results showed that 8-OHDPAT increased the respiratory cycle (RC) and expiratory time (TE) as well as reduced the integral amplitude (IA), but the changes of the inspiratory time (TI) were not statistically significant. PMPPI induced a significant decrease in RC, TE and TI, but the changes of IA were not statistically significant. The effect of 8-OHDPAT on the respiratory rhythm was partially reversed by additional application of PMPPI. Taken together with previous results, 5-HT(1A) receptors may play an important role in the modulation of RRDA in the medulla oblongata slice preparation of neonatal rats.

Contribution of the bronchial circulation to lung preservation.

PubMed

LoCicero, J; Massad, M; Matano, J; Greene, R; Dunn, M; Michaelis, L L

1991-05-01

Short preservation time still severely limits lung transplantation. To determine the effect of bronchial arterial flush preservation, we studied 54 dogs using the isolated perfused working lung model. After baseline measurements, lungs were flushed with lactated Ringer's solution (60 ml/kg at 8 degrees C) by one of three methods: pulmonary artery perfusion, bronchial artery perfusion through a 15 cm closed aortic segment, or simultaneous pulmonary-bronchial artery perfusion. These groups were further subdivided and tested after 0, 4, and 17 hours of storage at 4 degrees C (n = 6 each). Lungs were ventilated (flow rate 140 ml/kg/min; inspired oxygen fraction 0.21) and continuously reperfused with normothermic deoxygenated autologous blood in a closed loop. Measured variables were hemodynamics, aerodynamics, and leukocytes in bronchoalveolar lavage. Survival time was determined from initial reperfusion to failure of the lung to oxygenate. After 0 and 4 hours of storage, there was no significant difference in survival times. After 17 hours, lungs subjected to pulmonary-bronchial artery perfusion survived longer than those perfused via either the pulmonary or bronchial arteries alone (120 +/- 24 versus 38 +/- 14 or 52 +/- 16 minutes; p less than 0.01). Pulmonary artery pressure and resistance in all groups except at failure were never different from baseline values in the intact animal. Shunts in the pulmonary-bronchial artery perfusion groups were closest to baseline at onset (8% +/- 4%) and remained lower throughout reperfusion than in the groups subjected to pulmonary or bronchial artery perfusion alone. After 17 hours, static compliance of pulmonary artery-perfused lungs was worse than baseline (1.1 +/- 0.2 x 10(-2) versus 3.2 +/- 0.7 x 10(-2) L/cm H2O/sec; p less than 0.05), whereas compliance in the pulmonary-bronchial artery perfusion groups remained constant (3.6 +/- 1.5 x 10(-2) L/cm H2O/sec). Elastic work performed by lungs subjected to pulmonary-bronchial artery flushing at onset was significantly lower when these lungs were reperfused immediately (201 +/- 14 versus 295 +/- 35 gm-m/min for pulmonary artery-flushed lungs) or after 4 hours of storage (229 +/- 30 versus 290 +/- 24 gm-m/min for pulmonary artery-flushed lungs). Bronchoalveolar lavage after 17 hours in the group subjected to pulmonary bronchial artery flushing demonstrated leukocyte counts similar to those of intact lungs (45 +/- 5 versus 29 +/- 8/mm3) and significantly less than in lungs subjected to pulmonary or bronchial artery flushing (137 +/- 18 or 82 +/- 10/mm3, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)

Relationship of oscillating and average components of laser Doppler flowmetry signal

NASA Astrophysics Data System (ADS)

Mizeva, Irina; Frick, Peter; Podtaev, Sergey

2016-08-01

Signals from laser Doppler flowmeters widely used in intravital studies of skin blood flow include, along with a slowly varying average component, an oscillating part. However, in most clinical studies, pulsations are usually smoothed by data preprocessing and only the mean blood flow is analyzed. To reveal the relationship between average and oscillating perfusion components measured by a laser Doppler flowmeter, we examined the microvascular response to the contralateral cold pressor test recorded at two different sites of the hand: dorsal part of the arm and finger pad. Such a protocol makes it possible to provide a wide range of perfusion. The average perfusion always decreases during cooling, while the oscillating component demonstrates a differently directed response. The wavelet analysis of laser Doppler flowmetry (LDF) signals shows that the pulsatile component is nonlinearly related to the average perfusion. Under low perfusion, the amplitude of pulsations is proportional to its mean value, but, as perfusion increases, the amplitude of pulsations becomes lower. The type of response is defined by the basal perfusion and the degree of vasoconstriction caused by cooling. Interpretation of the results is complicated by the nonlinear transfer function of the LDF device, the contribution of which is studied using artificial examples.

Semipermeable Hollow Fiber Phantoms for Development and Validation of Perfusion-Sensitive MR Methods and Signal Models

PubMed Central

Anderson, J.R.; Ackerman, J.J.H.; Garbow, J.R.

2015-01-01

Two semipermeable, hollow fiber phantoms for the validation of perfusion-sensitive magnetic resonance methods and signal models are described. Semipermeable hollow fibers harvested from a standard commercial hemodialysis cartridge serve to mimic tissue capillary function. Flow of aqueous media through the fiber lumen is achieved with a laboratory-grade peristaltic pump. Diffusion of water and solute species (e.g., Gd-based contrast agent) occurs across the fiber wall, allowing exchange between the lumen and the extralumenal space. Phantom design attributes include: i) small physical size, ii) easy and low-cost construction, iii) definable compartment volumes, and iv) experimental control over media content and flow rate. PMID:26167136

How to evaluate the microcirculation: report of a round table conference

PubMed Central

De Backer, Daniel; Hollenberg, Steven; Boerma, Christiaan; Goedhart, Peter; Büchele, Gustavo; Ospina-Tascon, Gustavo; Dobbe, Iwan; Ince, Can

2007-01-01

Introduction Microvascular alterations may play an important role in the development of organ failure in critically ill patients and especially in sepsis. Recent advances in technology have allowed visualization of the microcirculation, but several scoring systems have been used so it is sometimes difficult to compare studies. This paper reports the results of a round table conference that was organized in Amsterdam in November 2006 in order to achieve consensus on image acquisition and analysis. Methods The participants convened to discuss the various aspects of image acquisition and the different scores, and a consensus statement was drafted using the Delphi methodology. Results The participants identified the following five key points for optimal image acquisition: five sites per organ, avoidance of pressure artifacts, elimination of secretions, adequate focus and contrast adjustment, and recording quality. The scores that can be used to describe numerically the microcirculatory images consist of the following: a measure of vessel density (total and perfused vessel density; two indices of perfusion of the vessels (proportion of perfused vessels and microcirculatory flow index); and a heterogeneity index. In addition, this information should be provided for all vessels and for small vessels (mostly capillaries) identified as smaller than 20 μm. Venular perfusion should be reported as a quality control index, because venules should always be perfused in the absence of pressure artifact. It is anticipated that although this information is currently obtained manually, it is likely that image analysis software will ease analysis in the future. Conclusion We proposed that scoring of the microcirculation should include an index of vascular density, assessment of capillary perfusion and a heterogeneity index. PMID:17845716

Semi-automated and automated glioma grading using dynamic susceptibility-weighted contrast-enhanced perfusion MRI relative cerebral blood volume measurements.

PubMed

Friedman, S N; Bambrough, P J; Kotsarini, C; Khandanpour, N; Hoggard, N

2012-12-01

Despite the established role of MRI in the diagnosis of brain tumours, histopathological assessment remains the clinically used technique, especially for the glioma group. Relative cerebral blood volume (rCBV) is a dynamic susceptibility-weighted contrast-enhanced perfusion MRI parameter that has been shown to correlate to tumour grade, but assessment requires a specialist and is time consuming. We developed analysis software to determine glioma gradings from perfusion rCBV scans in a manner that is quick, easy and does not require a specialist operator. MRI perfusion data from 47 patients with different histopathological grades of glioma were analysed with custom-designed software. Semi-automated analysis was performed with a specialist and non-specialist operator separately determining the maximum rCBV value corresponding to the tumour. Automated histogram analysis was performed by calculating the mean, standard deviation, median, mode, skewness and kurtosis of rCBV values. All values were compared with the histopathologically assessed tumour grade. A strong correlation between specialist and non-specialist observer measurements was found. Significantly different values were obtained between tumour grades using both semi-automated and automated techniques, consistent with previous results. The raw (unnormalised) data single-pixel maximum rCBV semi-automated analysis value had the strongest correlation with glioma grade. Standard deviation of the raw data had the strongest correlation of the automated analysis. Semi-automated calculation of raw maximum rCBV value was the best indicator of tumour grade and does not require a specialist operator. Both semi-automated and automated MRI perfusion techniques provide viable non-invasive alternatives to biopsy for glioma tumour grading.

The diagnostic performance of perfusion MRI for differentiating glioma recurrence from pseudoprogression: A meta-analysis.

PubMed

Wan, Bing; Wang, Siqi; Tu, Mengqi; Wu, Bo; Han, Ping; Xu, Haibo

2017-03-01

The purpose of this meta-analysis was to evaluate the diagnostic accuracy of perfusion magnetic resonance imaging (MRI) as a method for differentiating glioma recurrence from pseudoprogression. The PubMed, Embase, Cochrane Library, and Chinese Biomedical databases were searched comprehensively for relevant studies up to August 3, 2016 according to specific inclusion and exclusion criteria. The quality of the included studies was assessed according to the quality assessment of diagnostic accuracy studies (QUADAS-2). After performing heterogeneity and threshold effect tests, pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were calculated. Publication bias was evaluated visually by a funnel plot and quantitatively using Deek funnel plot asymmetry test. The area under the summary receiver operating characteristic curve was calculated to demonstrate the diagnostic performance of perfusion MRI. Eleven studies covering 416 patients and 418 lesions were included in this meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.88 (95% confidence interval [CI] 0.84-0.92), 0.77 (95% CI 0.69-0.84), 3.93 (95% CI 2.83-5.46), 0.16 (95% CI 0.11-0.22), and 27.17 (95% CI 14.96-49.35), respectively. The area under the summary receiver operating characteristic curve was 0.8899. There was no notable publication bias. Sensitivity analysis showed that the meta-analysis results were stable and credible. While perfusion MRI is not the ideal diagnostic method for differentiating glioma recurrence from pseudoprogression, it could improve diagnostic accuracy. Therefore, further research on combining perfusion MRI with other imaging modalities is warranted.

An in vitro lung model to assess true shunt fraction by multiple inert gas elimination.

PubMed

Varadarajan, Balamurugan; Vogt, Andreas; Hartwich, Volker; Vasireddy, Rakesh; Consiglio, Jolanda; Hugi-Mayr, Beate; Eberle, Balthasar

2017-01-01

The Multiple Inert Gas Elimination Technique, based on Micropore Membrane Inlet Mass Spectrometry, (MMIMS-MIGET) has been designed as a rapid and direct method to assess the full range of ventilation-to-perfusion (V/Q) ratios. MMIMS-MIGET distributions have not been assessed in an experimental setup with predefined V/Q-distributions. We aimed (I) to construct a novel in vitro lung model (IVLM) for the simulation of predefined V/Q distributions with five gas exchange compartments and (II) to correlate shunt fractions derived from MMIMS-MIGET with preset reference shunt values of the IVLM. Five hollow-fiber membrane oxygenators switched in parallel within a closed extracorporeal oxygenation circuit were ventilated with sweep gas (V) and perfused with human red cell suspension or saline (Q). Inert gas solution was infused into the perfusion circuit of the gas exchange assembly. Sweep gas flow (V) was kept constant and reference shunt fractions (IVLM-S) were established by bypassing one or more oxygenators with perfusate flow (Q). The derived shunt fractions (MM-S) were determined using MIGET by MMIMS from the retention data. Shunt derived by MMIMS-MIGET correlated well with preset reference shunt fractions. The in vitro lung model is a convenient system for the setup of predefined true shunt fractions in validation of MMIMS-MIGET.

(-)-Epigallocatechin-3-O-gallate (EGCG) attenuates the hemodynamics stimulated by caffeine through decrease of catecholamines release.

PubMed

Han, Jin-Yi; Moon, Yong-Jin; Han, Jong-Hyun; Kim, Jong-Hoon; Woo, Jae-Hoon; Yoo, Hwan-Soo; Hong, Jin Tae; Ahn, Hee-Yul; Hong, Jong-Myeon; Oh, Ki-Wan

2016-09-01

A human study of the effects on hemodynamics of caffeine and epigallocatechin-3-O-gallate (EGCG) was performed. Caffeine tablets (200 mg) were orally administered to healthy males aged between 25 and 35 years 30 min after oral administration of EGCG tablets (100 and 200 mg). The increase in BP induced by caffeine was inhibited when co-administrated with EGCG. We found that caffeine slightly decreased heart rate (HR) in the volunteers. Although EGCG enhanced HR reduction, the effect was not significant. In addition, caffeine increased blood catecholamine levels, but EGCG inhibited the increase in noradrenaline, adrenaline and dopamine levels induced by caffeine. Whether EGCG decreases the elevated HR and systolic perfusion pressure, and ventricular contractility induced by adrenergic agonists in the isolated rat heart was investigated. The modified Krebs-Henseleit solution was perfused through a Langendorff apparatus to the isolated hearts of rats. HR, systolic perfusion pressure, and developed maximal rates of contraction (+dP/dtmax) and relaxation (-dP/dtmax) were increased by epinephrine (EP) and isoproterenol (IP). In contrast, EGCG decreased the elevated HR, systolic perfusion pressure, and left ventricular ±dp/dtmax induced by EP and/or IP. In conclusion, EGCG could attenuate the hemodynamics stimulated by caffeine through decreasing catecholamine release.

An Herbal Nasal Drop Enhanced Frontal and Anterior Cingulate Cortex Activity

PubMed Central

Chan, Agnes S.; Cheung, Mei-chun; Sze, Sophia L.; Leung, Winnie W.; Shi, Dejian

2011-01-01

The present study examined the neuro-electrophysiological activity of the brain associated with the application of a herbal remedy developed by a Shaolin monk based upon the Chan healing principle of clearing the orifices (i.e., the nasal cavities). A repeated-measures design was used. Fourteen normal adults were administered herbal remedy and saline solution intranasally on separate sessions. Two intervals of eyes-closed resting EEG data were obtained individually before and after each administration. Results showed that only the herbal remedy but not the saline solution induced elevation in cordance, an index correlated with cerebral perfusion, in the anterior brain region. In addition, the activity of the anterior cingulate cortex (ACC), as examined by the LORETA analysis, was also increased after the application of the herbal remedy but not saline solution. The present study provided some preliminary evidence suggesting that the herbal nasal drop enhanced the activity of the frontal lobe and ACC. Implications for the potential clinical application of the herbal remedy to treat patients with frontal lobe disorders were discussed. PMID:19996154

Functional mechanism of lung mosaic CT attenuation: assessment with deep-inspiration breath-hold perfusion SPECT-CT fusion imaging and non-breath-hold Technegas SPECT.

PubMed

Suga, K; Yasuhiko, K; Iwanaga, H; Tokuda, O; Matsunaga, N

2009-01-01

The functional mechanism of lung mosaic computed tomography attenuation (MCA) in pulmonary vascular disease (PVD) and obstructive airway disease (OAD) has not yet been fully clarified. To clarify the mechanism of MCA in these diseases by assessing the relationship between regional lung function and CT attenuation change at MCA sites with the use of automated deep-inspiratory breath-hold (DIBrH) perfusion single-photon emission computed tomography (SPECT)-CT fusion images and non-breath-hold Technegas SPECT. Subjects were 42 PVD patients (31 pulmonary thromboembolism, four primary/two secondary pulmonary hypertension, and five Takayasu arteritis), 12 OAD patients (five acute asthma, four obliterative bronchiolitis, and three bronchiectasis), and 12 normal controls, all of whom had MCA on DIBrH CT. The relationship between regional lung function and CT attenuation change at the lung slices with MCA was assessed using DIBrH perfusion SPECT-CT fusion images and non-breath-hold Technegas SPECT. The severity of perfusion defects with or without MCA was quantified by regions-of-interest analysis. On DIBrH CT and perfusion SPECT, in contrast to no noticeable CT attenuation abnormality and fairly uniform perfusion in controls, 60 MCA and 274 perfusion defects in PVD patients, and 18 MCA and 61 defects in OAD patients were identified, with a total of 77 ventilation defects on Technegas SPECT in all patients. SPECT-CT correlation showed that, throughout the 78 MCA sites of all patients, lung perfusion was persistently decreased at low CT attenuation and preserved at intervening high CT attenuation, while lung ventilation was poorly correlated with CT attenuation change. The radioactivity ratios of reduced perfusion and the intervening preserved perfusion at the 78 perfusion defects with MCA were significantly lower than those at the remaining 257 defects without MCA (P<0.0001). Although further validation is required, our results indicate that heterogeneous pulmonary arterial perfusion may be a dominant mechanism of MCA in PVD and OAD.

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 radiation boost candidate for response-driven adaptive RT.« less

Dynamic variation in sapwood specific conductivity in six woody species

Treesearch

Jean-Christophe Domec; Frederick C. Meinzer; Barbara Lachenbruch; Johann Housset

2008-01-01

Our goals were to quantify how non-embolism inducing pressure gradients influence trunk sapwood specific conductivity (ks) and to compare the impacts of constant and varying pressure gradients on ks with KCl and H20 as the perfusion solutions. We studied six woody species (three conifers and three...

Differentiation between diverticulitis and colorectal cancer: quantitative CT perfusion measurements versus morphologic criteria--initial experience.

PubMed

Goh, Vicky; Halligan, Steve; Taylor, Stuart A; Burling, David; Bassett, Paul; Bartram, Clive I

2007-02-01

To determine whether computed tomographic (CT) perfusion measurements in prospectively recruited patients can be used to differentiate between diverticulitis and colorectal cancer and to compare this discrimination with that of standard morphologic criteria. After institutional review board approval and written informed consent were obtained, 60 patients (24 men, 36 women; mean age, 69 years; range, 33.5-90.4 years; 20 patients with cancer, 20 with diverticulitis, and 20 with inactive diverticular disease) underwent CT perfusion imaging at the level of the colonic abnormality, and perfusion parameters were calculated. Analysis of variance was used to investigate any differences in perfusion between the patient groups. Two independent observers also analyzed an abdominopelvic CT study obtained immediately after the CT perfusion study and noted standard morphologic criteria for differential diagnosis. The sensitivity and specificity of CT perfusion measurements for determining the diagnostic category were compared with morphologic criteria by means of multivariate analysis to identify the most discriminatory criteria. Mean blood volume, blood flow, transit time, and permeability were significantly different between patients with cancer and those with diverticulitis (P < .0001); patients with cancer had the highest blood volume, blood flow, and permeability and the shortest transit time. The most discriminatory criteria for determining diagnostic category were blood volume, transit time, permeability, and presence of pericolonic nodes (P = .05, .02, .04, and .02, respectively). Blood volume and blood flow each had a sensitivity of 80% and had specificity of 70% and 75%, respectively, for cancer in comparison with standard morphologic criteria: less than 5 cm of bowel involvement (45% sensitivity, 95% specificity), presence of a mass (85% sensitivity, 90% specificity), pericolonic inflammation (75% sensitivity, 5% specificity), and pericolonic nodes (90% sensitivity, 45% specificity). CT perfusion measurements enable differentiation and better discrimination, in comparison with morphologic criteria, between cancer and diverticulitis. (c) RSNA, 2007.

Nuclear cardiac

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

Slutsky, R.; Ashburn, W.L.

1982-01-01

The relationship between nuclear medicine and cardiology has continued to produce a surfeit of interesting, illuminating, and important reports involving the analysis of cardiac function, perfusion, and metabolism. To simplify the presentation, this review is broken down into three major subheadings: analysis of myocardial perfusion; imaging of the recent myocardial infarction; and the evaluation of myocardial function. There appears to be an increasingly important relationship between cardiology, particularly cardiac physiology, and nuclear imaging techniques. (KRM)

Mucosal injury induced by ischemia and reperfusion in the piglet intestine: Influences of age and feeding

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

Crissinger, K.D.; Granger, D.N.

1989-10-01

The pathogenesis of neonatal necrotizing enterocolitis is unknown, but enteral alimentation, infectious agents, and mesenteric ischemia have been frequently invoked as primary initiators of the disease. To define the vulnerability of the intestinal mucosa to ischemia and reperfusion in the developing piglet, we evaluated changes in mucosal permeability using plasma-to-lumen clearance of chromium 51-labeled ethylenediaminetetraacetic acid in the ileum of anesthetized 1-day-, 3-day-, 2-wk-, and 1-mo-old piglets as a function of (a) duration of intestinal ischemia (20, 40, or 60 min of total superior mesenteric artery occlusion), (b) feeding status (fasted or nursed), and (c) composition of luminal perfusate (balancedmore » salt solution vs. predigested cow milk-based formula). Baseline chromium 51-labeled ethylenediaminetetraacetic acid clearance was not significantly altered by ischemia, irrespective of duration, or feeding in all age groups. However, clearances were significantly elevated during reperfusion after 1 h of total intestinal ischemia in all age groups, whether fasted or fed. Reperfusion-induced increases in clearance did not differ among age groups when the bowel lumen was perfused with a balanced salt solution. However, luminal perfusion with formula resulted in higher clearances in 1-day-old piglets compared with all older animals. Thus, the neonatal intestine appears to be more vulnerable to mucosal injury induced by ischemia and reperfusion in the presence of formula than the intestine of older animals.« less

Protective effects of ethyl pyruvate in cisplatin-induced nephrotoxicity

PubMed Central

Kelle, Ilker; Akkoc, Hasan; Tunik, Selcuk; Nergiz, Yusuf; Erdinc, Meral; Erdinc, Levent

2014-01-01

This study was performed to investigate the effect of ethyl pyruvate on changes in renal functions and oxidative stress related renal injury caused by cisplatin (cis-dichlorodiammine platinum-II; CDDP). Male Wistar albino rats were divided into four groups (n = 8): (1) control group (1 ml Ringer's lactate solution i.p.); (2) ethyl pyruvate (EP) group (50 mg/kg Ringer's EP solution (REPS) i.p.); (3) cisplatin group (a single dose of cisplatin (5 mg/kg, i.p.); and (4) cisplatin + EP group (a single dose of cisplatin (5 mg/kg, i.p.) + REPS 50 mg/kg/day, i.p.) for five days. At the sixth day, kidneys of rats were mounted to a Langendorff apparatus. Renal perfusion pressures were recorded. Blood samples were taken for serum urea, creatinine, total oxidant status (TOS), total antioxidant status (TAS) and oxidative stres index (OSI) evaluations. Kidney tissues were obtained for malondialdehyde (MDA) analyses and histopathological examination. Perfusion pressures, serum urea, creatinine, TOS, OSI and tissue MDA levels were found significantly higher, whereas TAS was notably lower in cisplatin group. Histopathological examination showed apparent renal paranchymal injury in cisplatin group. In cisplatin + REPS group, perfusion pressures, serum urea, creatinine and tissue MDA levels were decreased. Moreover, EP co-administration provided less inflammatory cell infiltration, tubular dilatation, whereas TOS, TAS and OSI improved significantly versus cisplatin group. These findings show that EP has protective effects against cisplatin nephrotoxicity. PMID:26019553

Mucosal Perfusion Preservation by a Novel Shapeable Tissue Expander for Oral Reconstruction

PubMed Central

Barwinska, Daria; Garner, John; Davidson, Darrell D.; Cook, Todd G.; Eckert, George J.; Tholpady, Sunil S.; March, Keith L.; Park, Kinam

2017-01-01

Background: There are few methods for expanding oral mucosa, and these often cause complications such as tissue necrosis and expander eruption. This study examines mucosal blood perfusion following insertion of a novel shapeable hydrogel tissue expander (HTE). The canine model used subgingival insertion of HTE following tooth extraction and alveolar bone reduction. The primary goal of this study was to gain understanding of epithelial perfusion and reparative responses of gingival mucosa during HTE expansion. Methods: Nine Beagle dogs underwent bilateral premolar maxillary and mandibular tooth extraction. Three to four months later, HTE-contoured inserts were implanted submucosally under the buccal surface of the alveolar ridge. After removal and following a 6- to 7-month period of healing, new HTE implants were inserted at the same sites. The area was assessed weekly for tissue perfusion and volume of expansion. Biopsies for histological analysis were performed at the time of expander removal. Results: Within 2 weeks following the second insertion, blood flow returned to baseline (defined as the values of perfusion measurements at the presurgery assessment) and remained normal until hydrogel full expansion and removal. Volume expansion analysis revealed that the hydrogel doubled in volume. Histological assessment showed no macrophage or inflammatory infiltration of the mucosa. No superficial fibrosis, decreased vascularity, or mucosal change was seen. Conclusion: Maintenance of adequate tissue perfusion is a clinically important aspect of tissue expander performance to reduce risk of device loss or injury to the patient, particularly for areas with a history of previous surgeries. PMID:28894668

A pattern of cerebral perfusion anomalies between Major Depressive Disorder and Hashimoto Thyroiditis

PubMed Central

2011-01-01

Background This study aims to evaluate relationship between three different clinical conditions: Major Depressive Disorders (MDD), Hashimoto Thyroiditis (HT) and reduction in regional Cerebral Blood Flow (rCBF) in order to explore the possibility that patients with HT and MDD have specific pattern(s) of cerebral perfusion. Methods Design: Analysis of data derived from two separate data banks. Sample: 54 subjects, 32 with HT (29 women, mean age 38.8 ± 13.9); 22 without HT (19 women, mean age 36.5 ± 12.25). Assessment: Psychiatric diagnosis was carried out by Simplified Composite International Diagnostic Interview (CIDIS) using DSM-IV categories; cerebral perfusion was measured by 99 mTc-ECD SPECT. Statistical analysis was done through logistic regression. Results MDD appears to be associated with left frontal hypoperfusion, left temporal hypoperfusion, diffuse hypoperfusion and parietal perfusion asymmetry. A statistically significant association between parietal perfusion asymmetry and MDD was found only in the HT group. Conclusion In HT, MDD is characterized by a parietal flow asymmetry. However, the specificity of rCBF in MDD with HT should be confirmed in a control sample with consideration for other health conditions. Moreover, this should be investigated with a longitudinally designed study in order to determine a possible pathogenic cause. Future studies with a much larger sample size should clarify whether a particular perfusion pattern is associated with a specific course or symptom cluster of MDD. PMID:21910915

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.

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

NASA Astrophysics Data System (ADS)

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

2005-04-01

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

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.

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.

Effect of short-term hyperinsulinemia on the localization and expression of endothelin receptors A and B in lamellar tissue of the forelimbs of horses

PubMed Central

Gauff, Felicia C.; Patan-Zugaj, Bianca; Licka, Theresia F.

2014-01-01

Objective To determine the effect of short-term hyperinsulinemia on the localization and expression of endothelin receptor (ETR)-A and ETR-B in lamellar tissue of the forelimbs of horses. Samples Distal portion of 15 cadaveric forelimbs from healthy adult horses (1 limb/horse) obtained immediately after slaughter at an abattoir. Procedures Each forelimb was assigned to 1 of 3 treatment groups (perfused with autologous blood for 10 hours [control perfusion; n = 5], perfused with an insulin [142 ± 81 μU/mL] perfusate for 10 hours [insulinemic perfusion; 5], or not perfused [unperfused control; 5]). Immunohistochemical evaluation of lamellar tissue was performed to assess localization of ETR-A and ETR-B. Expression of ETR-A and ETR-B was measured semiquantitatively on a scale of 0 to 3 (0 = none, 1 = mild, 2 = moderate, and 3 = high-intensity staining) and quantitatively by means of gray value analysis with imaging software. Results In all specimens, ETR-A and ETR-B were localized in endothelium, smooth muscle cells, axons, and keratinocytes. Quantitative expression of ETR-A in the midportion of the primary epidermal lamellae for the insulinemic perfusion group (149 ± 16) was lower than that for the control perfusion group (158 ± 15). Expression of ETR-B in the primary epidermal lamellae tips for the insulinemic perfusion group (140 ± 29) was higher than that for the control perfusion group (114 ± 8). Conclusions and Clinical Relevance Hyperinsulinemia caused significant changes in endothelin receptor expression, which suggested that ETR antagonists might be beneficial for treatment of laminitis in horses. PMID:24669922

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

Sodium, phosphate, glucose, bicarbonate, and alanine interactions in the isolated proximal convoluted tubule of the rabbit kidney.

PubMed Central

Dennis, V W; Brazy, P C

1978-01-01

Interactions among the transport systems involved with sodium, bicarbonate, glucose, phosphate, and alanine absorption in isolated segments of the rabbit proximal convoluted tubule were examined with radioisotopic techniques to measure glucose, phosphate, and fluid absorption rates. The composition of the perfusate and bath varied from normal, physiological fluids to fluids deficient in a single solute. The deletion of glucose from the perfusate increased the lumen-to-bath flux of phosphate from 5.51 +/- 1.15 to 8.32 +/- 1.34 pmol/mm-min (P less than 0.01). Similar changes occurred when glucose transport was inhibited by phlorizin 10 micron in the perfusate, The deletion of alanine from the perfusate increased the lumen-to-bath flux of phosphate from 6.55 +/- 1.08 to 9.00 +/- 1.30 pmol/mm-min (P less than 0.01) but did not affect glucose transport significantly, 80.1 +/- 10.1 vs. 72.5 +/- 5.4 pmol/mm-min. Replacement of intraluminal sodium with choline, elimination of potassium from the bath, and removal of bicarbonate from the lumen and bath each reduced glucose, phosphate, and fluid absorption. These data indicate that the proximal absorptive processes for glucose and for phosphate include elements that are dependent upon some function of sodium transport. Additionally, the effects on phosphate transport of deleting glucose or alanine occur independent of any changes in net sodium transport and are opposite the effects of deleting bicarbonate. These differences may relate to the observations that the transport of glucose and alanine is electrogenic while that of bicarbonate is not. Regardless of possible mechanisms, the data demonstrate that important changes in the absorption rates of different solutes handled significantly by the proximal convoluted tubule may occur in response to changes in specific components of proximal sodium transport. PMID:670399

Acetylcholine released from cholinergic nerves contributes to cutaneous vasodilation during heat stress

NASA Technical Reports Server (NTRS)

Shibasaki, Manabu; Wilson, Thad E.; Cui, Jian; Crandall, Craig G.

2002-01-01

Nitric oxide (NO) contributes to active cutaneous vasodilation during a heat stress in humans. Given that acetylcholine is released from cholinergic nerves during whole body heating, coupled with evidence that acetylcholine causes vasodilation via NO mechanisms, it is possible that release of acetylcholine in the dermal space contributes to cutaneous vasodilation during a heat stress. To test this hypothesis, in seven subjects skin blood flow (SkBF) and sweat rate were simultaneously monitored over three microdialysis membranes placed in the dermal space of dorsal forearm skin. One membrane was perfused with the acetylcholinesterase inhibitor neostigmine (10 microM), the second membrane was perfused with the NO synthase inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME; 10 mM) dissolved in the aforementioned neostigmine solution (l-NAME(Neo)), and the third membrane was perfused with Ringer solution as a control site. Each subject was exposed to approximately 20 min of whole body heating via a water-perfused suit, which increased mean body temperature from 36.4 +/- 0.1 to 37.5 +/- 0.1 degrees C (P < 0.05). After the heat stress, SkBF at each site was normalized to its maximum value, identified by administration of 28 mM sodium nitroprusside. Mean body temperature threshold for cutaneous vasodilation was significantly lower at the neostigmine-treated site relative to the other sites (neostigmine: 36.6 +/- 0.1 degrees C, l-NAME(Neo): 37.1 +/- 0.1 degrees C, control: 36.9 +/- 0.1 degrees C), whereas no significant threshold difference was observed between the l-NAME(Neo)-treated and control sites. At the end of the heat stress, SkBF was not different between the neostigmine-treated and control sites, whereas SkBF at the l-NAME(Neo)-treated site was significantly lower than the other sites. These results suggest that acetylcholine released from cholinergic nerves is capable of modulating cutaneous vasodilation via NO synthase mechanisms early in the heat stress but not after substantial cutaneous vasodilation.

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

PubMed

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

2003-01-01

Mental stress (MS) is an important provocateur of myocardial ischemia in many patients with chronic coronary artery disease. The majority of laboratory assessments of ischemia in response to MS have included measurements of either myocardial perfusion or function alone. We performed this study to determine the relationship between alterations in perfusion and ventricular function during MS. Methods and results Twenty-eight patients with reversible perfusion defects on exercise or pharmacologic stress myocardial perfusion imaging (MPI) underwent simultaneous technetium 99m sestamibi single photon emission computed tomography (SPECT) MPI and transthoracic echocardiography at rest and during MS according to a mental arithmetic protocol. In all cases the MS study was performed within 4 weeks of the initial exercise or pharmacologic MPI that demonstrated ischemia. SPECT studies were analyzed visually with the use of a 13-segment model and quantitatively by semiautomated circumferential profile analysis. Echocardiograms were graded on a segmental model for regional wall motion on a 4-point scale. Of 28 patients, 18 (64%) had perfusion defects and/or left ventricular dysfunction develop during MS: 9 (32%) had myocardial perfusion defects develop, 6 (21%) had regional or global left ventricular dysfunction develop, and 3 (11%) had both perfusion defects and left ventricular dysfunction develop. The overall concordance between perfusion and function criteria for ischemia during MS was only 46%. Among 9 patients with MS-induced left ventricular dysfunction, 5 had new regional wall motion abnormalities and 4 had a global decrement in function. In patients with MS-induced ischemia by SPECT, the number of reversible perfusion defects was similar during both MS and exercise/pharmacologic stress (2.8 +/- 2.0 vs 3.5 +/- 1.8, P =.41). Hemodynamic changes during MS were similar whether patients were divided on the basis of perfusion defects or left ventricular dysfunction during MS. These data indicate the feasibility of simultaneous assessment of perfusion and function responses during MS. Flow and function responses to MS are frequently not concordant. These data suggest that MS-induced changes in perfusion may represent a different phenomenon than MS-induced changes in left ventricular function (either globally or regionally).

Diagnostic accuracy of stress perfusion CMR in comparison with quantitative coronary angiography: fully quantitative, semiquantitative, and qualitative assessment.

PubMed

Mordini, Federico E; Haddad, Tariq; Hsu, Li-Yueh; Kellman, Peter; Lowrey, Tracy B; Aletras, Anthony H; Bandettini, W Patricia; Arai, Andrew E

2014-01-01

This study's primary objective was to determine the sensitivity, specificity, and accuracy of fully quantitative stress perfusion cardiac magnetic resonance (CMR) versus a reference standard of quantitative coronary angiography. We hypothesized that fully quantitative analysis of stress perfusion CMR would have high diagnostic accuracy for identifying significant coronary artery stenosis and exceed the accuracy of semiquantitative measures of perfusion and qualitative interpretation. Relatively few studies apply fully quantitative CMR perfusion measures to patients with coronary disease and comparisons to semiquantitative and qualitative methods are limited. Dual bolus dipyridamole stress perfusion CMR exams were performed in 67 patients with clinical indications for assessment of myocardial ischemia. Stress perfusion images alone were analyzed with a fully quantitative perfusion (QP) method and 3 semiquantitative methods including contrast enhancement ratio, upslope index, and upslope integral. Comprehensive exams (cine imaging, stress/rest perfusion, late gadolinium enhancement) were analyzed qualitatively with 2 methods including the Duke algorithm and standard clinical interpretation. A 70% or greater stenosis by quantitative coronary angiography was considered abnormal. The optimum diagnostic threshold for QP determined by receiver-operating characteristic curve occurred when endocardial flow decreased to <50% of mean epicardial flow, which yielded a sensitivity of 87% and specificity of 93%. The area under the curve for QP was 92%, which was superior to semiquantitative methods: contrast enhancement ratio: 78%; upslope index: 82%; and upslope integral: 75% (p = 0.011, p = 0.019, p = 0.004 vs. QP, respectively). Area under the curve for QP was also superior to qualitative methods: Duke algorithm: 70%; and clinical interpretation: 78% (p < 0.001 and p < 0.001 vs. QP, respectively). Fully quantitative stress perfusion CMR has high diagnostic accuracy for detecting obstructive coronary artery disease. QP outperforms semiquantitative measures of perfusion and qualitative methods that incorporate a combination of cine, perfusion, and late gadolinium enhancement imaging. These findings suggest a potential clinical role for quantitative stress perfusion CMR. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

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 available for this article.

Methods of Producing Freeze-Dried Acellular Vascular, Peripheral Nerve and Generic Tissue Grafts for the Treatment of Combat Casualties

DTIC Science & Technology

1998-02-01

wcollection of infrma tion. Send comments re8ardinfg this burden estimate or any Other aspect of this • collection of informationj ncluding sug(estions...and the vessels were then immedi- ately immersed in Vitrification Solution Maltodextrin (VSMD), comprised of a 75% buffered solution of maltodextrin ...concentration of 75% maltodextrin is very viscous and unlikely to passively perfuse the graft. Secondly, the vessels were sutured to teflon struts which

Bioreactor-Based Online Recovery of Human Progenitor Cells with Uncompromised Regenerative Potential: A Bone Tissue Engineering Perspective

PubMed Central

Sonnaert, Maarten; Luyten, Frank P.; Papantoniou, Ioannis

2015-01-01

The use of a 3D perfusion culture environment for stem cell expansion has been shown to be beneficial for maintenance of the original cell functionality but due to several system inherent characteristics such as the presence of extracellular matrix, the continued development and implementation of 3D perfusion bioreactor technologies is hampered. Therefore, this study developed a methodology for harvesting a progenitor cell population from a 3D open porous culture surface after expansion in a perfusion bioreactor and performed a functional characterization of the expanded cells. An initial screening showed collagenase to be the most interesting reagent to release the cells from the 3D culture surface as it resulted in high yields without compromising cell viability. Subsequently a Design of Experiment approach was used to obtain optimized 3D harvest conditions by assessing the interplay of flow rate, collagenase concentration and incubation time on the harvest efficiency, viability and single cell fraction. Cells that were recovered with the optimized harvest protocol, by perfusing a 880 U/ml collagenase solution for 7 hours at a flow rate of 4 ml/min, were thereafter functionally analyzed for their characteristics as expanded progenitor cell population. As both the in vitro tri-lineage differentiation capacity and the in vivo bone forming potential were maintained after 3D perfusion bioreactor expansion we concluded that the developed seeding, culture and harvest processes did not significantly compromise the viability and potency of the cells and can contribute to the future development of integrated bioprocesses for stem cell expansion. PMID:26313143

Bioreactor-Based Online Recovery of Human Progenitor Cells with Uncompromised Regenerative Potential: A Bone Tissue Engineering Perspective.

PubMed

Sonnaert, Maarten; Luyten, Frank P; Schrooten, Jan; Papantoniou, Ioannis

2015-01-01

The use of a 3D perfusion culture environment for stem cell expansion has been shown to be beneficial for maintenance of the original cell functionality but due to several system inherent characteristics such as the presence of extracellular matrix, the continued development and implementation of 3D perfusion bioreactor technologies is hampered. Therefore, this study developed a methodology for harvesting a progenitor cell population from a 3D open porous culture surface after expansion in a perfusion bioreactor and performed a functional characterization of the expanded cells. An initial screening showed collagenase to be the most interesting reagent to release the cells from the 3D culture surface as it resulted in high yields without compromising cell viability. Subsequently a Design of Experiment approach was used to obtain optimized 3D harvest conditions by assessing the interplay of flow rate, collagenase concentration and incubation time on the harvest efficiency, viability and single cell fraction. Cells that were recovered with the optimized harvest protocol, by perfusing a 880 U/ml collagenase solution for 7 hours at a flow rate of 4 ml/min, were thereafter functionally analyzed for their characteristics as expanded progenitor cell population. As both the in vitro tri-lineage differentiation capacity and the in vivo bone forming potential were maintained after 3D perfusion bioreactor expansion we concluded that the developed seeding, culture and harvest processes did not significantly compromise the viability and potency of the cells and can contribute to the future development of integrated bioprocesses for stem cell expansion.

Hypertonic sodium lactate reverses brain oxygenation and metabolism dysfunction after traumatic brain injury.

PubMed

Millet, A; Cuisinier, A; Bouzat, P; Batandier, C; Lemasson, B; Stupar, V; Pernet-Gallay, K; Crespy, T; Barbier, E L; Payen, J F

2018-06-01

The mechanisms by which hypertonic sodium lactate (HSL) solution act in injured brain are unclear. We investigated the effects of HSL on brain metabolism, oxygenation, and perfusion in a rodent model of diffuse traumatic brain injury (TBI). Thirty minutes after trauma, anaesthetised adult rats were randomly assigned to receive a 3 h infusion of either a saline solution (TBI-saline group) or HSL (TBI-HSL group). The sham-saline and sham-HSL groups received no insult. Three series of experiments were conducted up to 4 h after TBI (or equivalent) to investigate: 1) brain oedema using diffusion-weighted magnetic resonance imaging and brain metabolism using localized 1 H-magnetic resonance spectroscopy (n = 10 rats per group). The respiratory control ratio was then determined using oxygraphic analysis of extracted mitochondria, 2) brain oxygenation and perfusion using quantitative blood-oxygenation-level-dependent magnetic resonance approach (n = 10 rats per group), and 3) mitochondrial ultrastructural changes (n = 1 rat per group). Compared with the TBI-saline group, the TBI-HSL and the sham-operated groups had reduced brain oedema. Concomitantly, the TBI-HSL group had lower intracellular lactate/creatine ratio [0.049 (0.047-0.098) vs 0.097 (0.079-0.157); P < 0.05], higher mitochondrial respiratory control ratio, higher tissue oxygen saturation [77% (71-79) vs 66% (55-73); P < 0.05], and reduced mitochondrial cristae thickness in astrocytes [27.5 (22.5-38.4) nm vs 38.4 (31.0-47.5) nm; P < 0.01] compared with the TBI-saline group. Serum sodium and lactate concentrations and serum osmolality were higher in the TBI-HSL than in the TBI-saline group. These findings indicate that the hypertonic sodium lactate solution can reverse brain oxygenation and metabolism dysfunction after traumatic brain injury through vasodilatory, mitochondrial, and anti-oedema effects. Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

Evaluation of changes in perfusion defect and left ventricular systolic function using Tc-99m Tetrofosmin single photon emission computed tomography over 3 month period in patients of Acute Myocardial Infarction undergoing primary angioplasty.

PubMed

Kumar, Avs Anil; Kumar, P G; Swami, Ajay; Dinker, Yateendra

2018-01-01

After a primary transluminal coronary angioplasty (PTCA) following AMI (acute myocardial infarction), the perfusion defect and LV (left ventricular) function recover/change over a period of time. The analysis immediately after the procedure may not be true depiction of the exact success of the procedure. There is varying and scanty information available on the natural course of changes in these parameters after a successful PTCA. We hypothesized that majority of change occurs at 3-4 month period. Hence, we undertook this study on the natural course of recovery/changes occurring in perfusion defect size and LV function in first 3 months after primary angioplasty MATERIAL AND METHODS: 30 consecutive cases of first AMI who were taken up for Primary angioplasty were enrolled into the study. Resting MPI(Myocardial perfusion imaging) was done within 24-72 hrs of admission using Tc-99m-Tetrofosmin and after 10-14 weeks. Analysis of LVEF (left ventricular ejection fraction), summed segmental score and extent of perfusion defect was done. Images were processed using autocardiac software of emory tool box and quantification was done using QPS (quantitative perfusion SPECT) and QGS (qualitative perfusion SPECT) softwares. 20 segment scoring method was used for quantification on bull's eye images. Student t test (two tailed, dependent) was used to find the significance of study parameters on continuous scale within each group. Effect size was computed to find the effect. Pearson correlation between perfusion defect and LVEF was performed at acute stage and after 10-14 weeks. The average acute perfusion defect extent was 19.76 ± 12.89% which after 3months became 16.79 ± 12.61%. The summed segmental score changed from 14.31 ± 10.58 to 11.38 ± 10.03 and LVEF improved from 48.40 ± 13.15% to 53.37 ± 12.8%. There was significant improvement in LVEF from acute setting to 10-14 weeks (p = 0.001). There was significant lowering of summed score (p = 0.007). Perfusion defect size showed significant reduction (p = 0.030). Three patients showed deterioration in perfusion defect size and in summed score with reduction in LVEF. Four patients had no change in any of the parameters. Correlation between perfusion defect and LVEF was strong both at baseline (r = -0.705, p < 0.001) and after 10-18 weeks (r = -0.766, p < 0.001). The changes we found in 3 months are similar to earlier studies and also to studies using follow up at 6 months to 1 year. We feel that 3 months is a good enough time to accurately assess the success of primary angioplasty.

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.

Soft Plumbing: Direct-Writing and Controllable Perfusion of Tubular Soft Materials

NASA Astrophysics Data System (ADS)

Guenther, Axel; Omoruwa, Patricia; Chen, Haotian; McAllister, Arianna; Jeronimo, Mark; Malladi, Shashi; Hakimi, Navid; Cao, Li; Ramchandran, Arun

2016-11-01

Tubular and ductular structures are abundant in tissues in a wide variety of diameters, wall thicknesses, and compositions. In spite of their relevance to engineered tissues, organs-on-chips and soft robotics, the rapid and consistent preparation of tubular structures remains a challenge. Here, we use a microfabricated printhead to direct-write biopolymeric tubes with dimensional and compositional control. A biopolymer solution is introduced to the center layer of the printhead, and the confining fluids to the top and the bottom layers. The radially flowing biopolymer solution is sandwiched between confining solutions that initiate gelation, initially assuming the shape of a funnel until emerging through a cylindrical confinement as a continuous biopolymer tube. Tubular constructs of sodium alginate and collagen I were obtained with inner diameters (0.6-2.2mm) and wall thicknesses (0.1-0.4mm) in favorable agreement with predictions of analytical models. We obtained homogeneous tubes with smooth and buckled walls and heterotypic constructs that possessed compositions that vary along the tube circumference or radius. Ductular soft materials were reversibly hosted in 3D printed fluidic devices for the perfusion at well-defined transmural pressures to explore the rich variety of dynamical features associated with collapsible tubes that include buckling, complete collapse, and self-oscillation.

Desferrioxamine in warm reperfusion media decreases liver injury aggravated by cold storage

PubMed Central

Arthur, Peter G; Niu, Xian-Wa; Huang, Wen-Hua; DeBoer, Bastiaan; Lai, Ching Tat; Rossi, Enrico; Joseph, John; Jeffrey, Gary P

2013-01-01

AIM: To evaluate whether desferrioxamine decreases ischemia and perfusion injury aggravated by cold storage (CS) in a rat liver perfusion model. METHODS: Isolated rat livers were kept in CS in University of Wisconsin Solution for 20 h at 4 °C, then exposed to 25 min of warm ischemia (WI) at 37 °C followed by 2 h of warm perfusion (WP) at 37 °C with oxygenated (95% oxygen and 5% carbon dioxide) Krebs-Henseleit buffer. Desferrioxamine (DFO), an iron chelator, was added at different stages of storage, ischemia and perfusion: in CS only, in WI only, in WP only, in WI and perfusion, or in all stages. Effluent samples were collected after CS and after WI. Perfusate samples and bile were collected every 30 min (0, 0.5, 1, 1.5 and 2 h) during liver perfusion. Cellular injury was assessed by the determination of lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) in the effluent and perfusate samples. Total iron was analysed in the perfusate samples. After WP, the liver was collected for the determination of liver swelling (wet to dry ratio) and liver morphological examination (hematoxylin and eosin staining). RESULTS: Increased CS time caused increased liver dysfunction during WP. After 2 h of WP, liver injury was indicated by increased release of AST (0.5 h CS: 9.4 ± 2.2 U/g liver vs 20 h CS: 45.9 ± 10.8 U/g liver, P < 0.05) and LDH (0.5 h CS: 59 ± 14 U/g liver vs 20 h CS: 297 ± 71 U/g liver, P < 0.05). There was an associated increase in iron release into the perfusate (0.5 h CS: 0.11 ± 0.03 μmoL/g liver vs 20 h CS: 0.58 ± 0.10 μmoL/g liver, P < 0.05) and reduction in bile flow (0.5 h CS: 194 ± 12 μL/g vs 20 h CS: 71 ± 8 μL/g liver, P < 0.05). When DFO was added during WI and WP following 20 h of CS, release of iron into the perfusate was decreased (DFO absent 0.58 ± 0.10 μmoL/g liver vs DFO present 0.31 ± 0.06 μmoL/g liver, P < 0.05), and liver function substantially improved with decreased release of AST (DFO absent 45.9 ± 10.8 U/g liver vs DFO present 8.1 ± 0.9 U/g liver, P < 0.05) and LDH (DFO absent 297 ± 71 U/g liver vs DFO present 56 ± 7 U/g liver, P < 0.05), and increased bile flow (DFO absent 71 ± 8 μL/g liver vs DFO present 237 ± 36 μL/g liver, P < 0.05). DFO was also shown to improve liver morphology after WP. Cellular injury (the release of LDH and AST) was significantly reduced with the addition of DFO in CS medium but to a lesser extent compared to the addition of DFO in WP or WI and perfusion. There was no effect on liver swelling or bile flow when DFO was only added to the CS medium. CONCLUSION: DFO added during WI and perfusion decreased liver perfusion injury aggravated by extended CS. PMID:23429835

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.

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.

Automated three-dimensional quantification of myocardial perfusion and brain SPECT.

PubMed

Slomka, P J; Radau, P; Hurwitz, G A; Dey, D

2001-01-01

To allow automated and objective reading of nuclear medicine tomography, we have developed a set of tools for clinical analysis of myocardial perfusion tomography (PERFIT) and Brain SPECT/PET (BRASS). We exploit algorithms for image registration and use three-dimensional (3D) "normal models" for individual patient comparisons to composite datasets on a "voxel-by-voxel basis" in order to automatically determine the statistically significant abnormalities. A multistage, 3D iterative inter-subject registration of patient images to normal templates is applied, including automated masking of the external activity before final fit. In separate projects, the software has been applied to the analysis of myocardial perfusion SPECT, as well as brain SPECT and PET data. Automatic reading was consistent with visual analysis; it can be applied to the whole spectrum of clinical images, and aid physicians in the daily interpretation of tomographic nuclear medicine images.

Mathematical model formulation and validation of water and solute transport in whole hamster pancreatic islets.

PubMed

Benson, James D; Benson, Charles T; Critser, John K

2014-08-01

Optimization of cryopreservation protocols for cells and tissues requires accurate models of heat and mass transport. Model selection often depends on the configuration of the tissue. Here, a mathematical and conceptual model of water and solute transport for whole hamster pancreatic islets has been developed and experimentally validated incorporating fundamental biophysical data from previous studies on individual hamster islet cells while retaining whole-islet structural information. It describes coupled transport of water and solutes through the islet by three methods: intracellularly, intercellularly, and in combination. In particular we use domain decomposition techniques to couple a transmembrane flux model with an interstitial mass transfer model. The only significant undetermined variable is the cellular surface area which is in contact with the intercellularly transported solutes, Ais. The model was validated and Ais determined using a 3×3 factorial experimental design blocked for experimental day. Whole islet physical experiments were compared with model predictions at three temperatures, three perfusing solutions, and three islet size groups. A mean of 4.4 islets were compared at each of the 27 experimental conditions and found to correlate with a coefficient of determination of 0.87±0.06 (mean ± SD). Only the treatment variable of perfusing solution was found to be significant (p<0.05). We have devised a model that retains much of the intrinsic geometric configuration of the system, and thus fewer laboratory experiments are needed to determine model parameters and thus to develop new optimized cryopreservation protocols. Additionally, extensions to ovarian follicles and other concentric tissue structures may be made. Copyright © 2014 Elsevier Inc. All rights reserved.

Dynamic contrast-enhanced perfusion area-detector CT assessed with various mathematical models: Its capability for therapeutic outcome prediction for non-small cell lung cancer patients with chemoradiotherapy as compared with that of FDG-PET/CT.

PubMed

Ohno, Yoshiharu; Fujisawa, Yasuko; Koyama, Hisanobu; Kishida, Yuji; Seki, Shinichiro; Sugihara, Naoki; Yoshikawa, Takeshi

2017-01-01

To directly compare the capability of dynamic first-pass contrast-enhanced (CE-) perfusion area-detector CT (ADCT) and PET/CT for early prediction of treatment response, disease progression and overall survival of non-small cell carcinoma (NSCLC) patients treated with chemoradiotherapy. Fifty-three consecutive Stage IIIB NSCLC patients who had undergone PET/CT, dynamic first-pass CE-perfusion ADCT, chemoradiotherapy, and follow-up examination were enrolled in this study. They were divided into two groups: 1) complete or partial response (CR+PR) and 2) stable or progressive disease (SD+PD). Pulmonary arterial and systemic arterial perfusions and total perfusion were assessed at targeted lesions with the dual-input maximum slope method, permeability surface and distribution volume with the Patlak plot method, tumor perfusion with the single-input maximum slope method, and SUV max , and results were averaged to determine final values for each patient. Next, step-wise regression analysis was used to determine which indices were the most useful for predicting therapeutic effect. Finally, overall survival of responders and non-responders assessed by using the indices that had a significant effect on prediction of therapeutic outcome was statistically compared. The step-wise regression test showed that therapeutic effect (r 2 =0.63, p=0.01) was significantly affected by the following three factors in order of magnitude of impact: systemic arterial perfusion, total perfusion, and SUV max . Mean overall survival showed a significant difference for total perfusion (p=0.003) and systemic arterial perfusion (p=0.04). Dynamic first-pass CE-perfusion ADCT as well as PET/CT are useful for treatment response prediction in NSCLC patients treated with chemoradiotherapy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Continuous production of lactic acid from molasses by perfusion culture of Lactococcus lactis using a stirred ceramic membrane reactor.

PubMed

Ohashi, R; Yamamoto, T; Suzuki, T

1999-01-01

A perfusion culture system was used for continuous production of lactic acid by retaining cells at a high density of Lactococcus lactis in a stirred ceramic membrane reactor (SCMR). After the cell concentration increased to 248 g/l, half of the culture broth volume was replaced with the fermentation medium. Subsequently, a substrate solution containing glucose (run 1) or molasses (run 2) was continuously supplied to the cells retained in the SCMR. Simultaneously, the culture supernatant was extracted using a ceramic filter with a pore size of 0.2 mum. The dilution rate was initially set at 0.4 h(-1) and gradually decreased to 0.2 h(-1) due to reduction in the permeability of the filter. The concentration of glucose in the substrate solution was adjusted to 60 g/l for the transition and the first period until 240 h, 90 g/l for the second period from 240 h to 440 h, and 70 g/l for the third period from 440 h to 643 h. The average concentration of lactic acid in the filtrate reached 46 g/l in the first period, 43 g/l in the second period, and 33 g/l for the third period. The productivity obtained for the first period reached 15.8 g.l(-1).h(-1), twice as much as that achieved in repeated batch fermentations. Based on the results obtained in run 1, the substrate solution containing 120 g/l of molasses was continuously supplied for 240 h in run 2. The concentration and productivity of lactic acid reached 40 g/l and 10.6 g.l(-1).h(-1), respectively, by continuously replenishing the culture medium at a dilution rate of 0.26 h(-1). These results demonstrated that the filtration capacity of the SCMR was sufficient for a continuous and rapid replenishment of molasses solution from the dense cell culture and, therefore, the perfusion culture system is considered to provide a low-cost process for continuous production of lactic acid from cheap resources.

Assay of lysergic acid diethylamide and its passage from blood into the perfused cerebral ventricles

PubMed Central

Dras̆koci, M.

1960-01-01

On the isolated rat uterus, lysergic acid diethylamide had an oxytocic action in a concentration of 2×10-8; in smaller concentrations (10-9 to 10-10), which had no stimulating effect of their own, it potentiated acetylcholine-induced contractions. This potentiating effect was made the basis for assaying minute amounts of lysergic acid diethylamide. The method was used to assay this substance in plasma of cats during its intravenous infusion at a rate of 10 μg./min./kg. During these infusions 0.4 to 2 ng./min. of lysergic acid diethylamide passed into the cerebral ventricles perfused with a salt solution of a composition resembling that of cerebrospinal fluid. PMID:13818017

Experimental studies of gastric dysfunction in motion sickness: The effect of gastric and vestibular stimulation on the vagal and splanchnic gastric efferents

NASA Technical Reports Server (NTRS)

Niijima, A.; Jiang, Z. Y.; Daunton, Nancy G.; Fox, Robert A.

1991-01-01

The experiments were conducted in anaesthetized rats. In the first part of the experiments, the effect of CuSO4 on the afferent activity in the gastric branch of the vagus nerve was investigated. Gastric perfusion of CuSO4 solution (0.04 percent and 0.08 percent) provoked an increase in afferent activity. In the second part of the experiments, the reflex effects of gastric perfusion of CuSO4 solution, repetitive stimulation of the gastric vagus nerve, and caloric stimulation of the right vestibular apparatus (5-18 C water) on gastric autonomic outflow were investigated. The results of these experiments showed that these three different types of stimulation caused an inhibition in efferent activity of the gastric vagus nerve and a slight activation of the splanchnic gastric efferents. The summation of the effect of each stimulation was also observed. These results, therefore, provide evidence for a possible integrative inhibitory function of the vagal gastric center as well as an excitatory function of gastric sympathetic motoneurons in relation to motion sickness.

[Antiarrhythmic and cardioprotective effect of stimulation of delta1-opiate receptors in myocardial ischemia and reperfusion].

PubMed

Lasukova, T V; Krylatov, A V; Maslov, L N; Lishmanov, Iu B; Gross, G J; Podoksenov, Iu K; Podoksenov, A Iu

2004-01-01

Pretreatment with intravenous peptide delta1-opioid receptor (OR) agonist DPDPE (0.5 mg/kg) decreases the incidence of occlusion (10 min) and reperfusion (10 min) arrhythmias in rats. The agonist of delta2-OR DSLET has no effect on arrhythmias in coronary artery occlusion and reperfusion. Pretreatment with selective delta-antagonists ICI 174,864 (2.5 mg/kg) eliminates an antiarrhythmic effect of DPDPE. The addition of DPDPE to the perfusion solution in a final concentration of 0.1 mg/l and/or 0.5 mg/l fifteen min before ischemia also decreases the incidence of reperfusion arrhythmias in a concentration-dependent manner. The addition of DPDPE to the perfusion solution in a final concentration of 0.1 mg/l decreases creatine kinase levels in the coronary sinus effluent. However, DPDPE has no cardioprotective effect in a concentration of 0.5 mg/l or after intravenous administration. It is suggested that antiarrhythmic and cardioprotective effects of DPDPE during reperfusion may be due to stimulation of cardiac delta1-receptors.

Nociception from blood vessels is independent of the sympathetic nervous system under physiological conditions in humans.

PubMed

Kindgen-Milles, D; Holthusen, H

1997-06-05

To test the hypothesis that vascular pain depends on sympathetic drive under physiological conditions we studied the effects of both alpha-adrenoceptor stimulation by noradrenaline and alpha-adrenoceptor blockade by phentolamine on the intensity of physicochemically evoked pain from veins in humans. In seven healthy volunteers, a vascularly isolated hand vein segment was perfused continuously with noradrenaline (6 x 10(-9)-6 x 10(-6) M), or phentolamine (1.24 x 10(-4) M). Pain was evoked by intraluminal electrostimulation or by injection of hyperosmolar saline during control perfusion of isoosmolar saline and after each noradrenaline concentration, as well as after perfusion of phentolamine. Subjects rated pain intensity continuously on an electronically controlled visual analogue scale (VAS) between 0% VAS (no pain) and 100% VAS (tolerance maximum). Intravenous electrostimulation as well as hyperosmolar solutions evoked pain in each subject. The intensity of pain was neither influenced by noradrenaline, nor by phentolamine, so that nociception from blood vessels is unlikely to be modulated by the sympathetic nervous system under physiological conditions in humans.

Lesional perfusion abnormalities in Leigh disease demonstrated by arterial spin labeling correlate with disease activity.

PubMed

Whitehead, Matthew T; Lee, Bonmyong; Gropman, Andrea

2016-08-01

Leigh disease is a metabolic disorder of the mitochondrial respiratory chain culminating in symmetrical necrotizing lesions in the deep gray nuclei or brainstem. Apart from classic gliotic/necrotic lesions, small-vessel proliferation is also characteristic on histopathology. We have observed lesional hyperperfusion on arterial spin-labeling (ASL) sequence in children with Leigh disease. In this cross-sectional analysis, we evaluated lesional ASL perfusion characteristics in children with Leigh syndrome. We searched the imaging database from an academic children's hospital for "arterial spin labeling, perfusion, necrosis, lactate, and Leigh" to build a cohort of children for retrospective analysis. We reviewed each child's medical record to confirm a diagnosis of Leigh disease, excluding exams with artifact, technical limitations, and without ASL images. We evaluated the degree and extent of cerebral blood flow and relationship to brain lesions. Images were compared to normal exams from an aged-matche cohort. The database search yielded 45 exams; 30 were excluded. We evaluated 15 exams from 8 children with Leigh disease and 15 age-matched normal exams. In general, Leigh brain perfusion ranged from hyperintense (n=10) to hypointense (n=5). Necrotic lesions appeared hypointense/hypoperfused. Active lesions with associated restricted diffusion demonstrated hyperperfusion. ASL perfusion patterns differed significantly from those on age-matched normal studies (P=<.0001). Disease activity positively correlated with cerebral deep gray nuclei hyperperfusion (P=0.0037) and lesion grade (P=0.0256). Children with Leigh disease have abnormal perfusion of brain lesions. Hyperperfusion can be found in active brain lesions, possibly associated with small-vessel proliferation characteristic of the disease.

State-of the-art review on the renal and visceral protection during open thoracoabdominal aortic aneurysm repair.

PubMed

Waked, Karl; Schepens, Marc

2018-01-01

During open thoracoabdominal aortic aneurysm repair (OTAAAR), there is an inevitable organ ischemic period that occurs when the abdominal arteries are being reattached to the aortic graft. Despite various protective techniques, the incidence of renal and visceral complications remains substantial. This state-of-the-art review gives an overview of the current and most evidence-based organ protection methods during OTAAAR, based on the most recent publications and personal experience. An electronic search was performed in four medical databases, using the following MeSH terms: thoracoabdominal aneurysm, TAAAR, visceral protection, renal protection, kidney, perfusion, and intestines. Every publication type was considered. The literature search was ended on August 31st, 2017. The left heart bypass (LHB) is currently the most frequent adjunct to provide distal aortic perfusion (DAP) during aortic clamping. Together with systemic hypothermia, it forms the cornerstone in organ protection during aortic clamping. Further renal protection can be obtained by selective renal perfusion (SRP) with cold blood or cold crystalloid solution, the latter enriched with mannitol. The perfusion should be administered in a volume- and pressure-controlled way and, if possible, by use of a pulsatile pump. Selective visceral perfusion (SVP) is not routinely used, as it does not provide adequate blood flow for visceral protection. The best way to protect the intestines is by minimizing the ischemic time. The preservation of renal and visceral function after OTAAAR can only be obtained with specific strategies before, during, and after the operation. This involves a series of measures, including selective digestive decontamination (SDD), avoidance of nephrotoxic drugs, minimizing the renal and intestinal ischemic time, systemic cooling, avoidance of hemodynamic instability, and regional protective perfusion of the kidneys. Future innovations in catheters, cardiac bypass flow types, mechanical components, hybrid vascular grafts, and pharmaceutical protection measures will hopefully further reduce organ complications.

Novel methods for parameter-based analysis of myocardial tissue in MR images

NASA Astrophysics Data System (ADS)

Hennemuth, A.; Behrens, S.; Kuehnel, C.; Oeltze, S.; Konrad, O.; Peitgen, H.-O.

2007-03-01

The analysis of myocardial tissue with contrast-enhanced MR yields multiple parameters, which can be used to classify the examined tissue. Perfusion images are often distorted by motion, while late enhancement images are acquired with a different size and resolution. Therefore, it is common to reduce the analysis to a visual inspection, or to the examination of parameters related to the 17-segment-model proposed by the American Heart Association (AHA). As this simplification comes along with a considerable loss of information, our purpose is to provide methods for a more accurate analysis regarding topological and functional tissue features. In order to achieve this, we implemented registration methods for the motion correction of the perfusion sequence and the matching of the late enhancement information onto the perfusion image and vice versa. For the motion corrected perfusion sequence, vector images containing the voxel enhancement curves' semi-quantitative parameters are derived. The resulting vector images are combined with the late enhancement information and form the basis for the tissue examination. For the exploration of data we propose different modes: the inspection of the enhancement curves and parameter distribution in areas automatically segmented using the late enhancement information, the inspection of regions segmented in parameter space by user defined threshold intervals and the topological comparison of regions segmented with different settings. Results showed a more accurate detection of distorted regions in comparison to the AHA-model-based evaluation.

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

Hydrogen Gas Ameliorates Hepatic Reperfusion Injury After Prolonged Cold Preservation in Isolated Perfused Rat Liver.

PubMed

Shimada, Shingo; Wakayama, Kenji; Fukai, Moto; Shimamura, Tsuyoshi; Ishikawa, Takahisa; Fukumori, Daisuke; Shibata, Maki; Yamashita, Kenichiro; Kimura, Taichi; Todo, Satoru; Ohsawa, Ikuroh; Taketomi, Akinobu

2016-12-01

Hydrogen gas reduces ischemia and reperfusion injury (IRI) in the liver and other organs. However, the precise mechanism remains elusive. We investigated whether hydrogen gas ameliorated hepatic I/R injury after cold preservation. Rat liver was subjected to 48-h cold storage in University of Wisconsin solution. The graft was reperfused with oxygenated buffer with or without hydrogen at 37° for 90 min on an isolated perfusion apparatus, comprising the H 2 (+) and H 2 (-) groups, respectively. In the control group (CT), grafts were reperfused immediately without preservation. Graft function, injury, and circulatory status were assessed throughout the perfusion. Tissue samples at the end of perfusion were collected to determine histopathology, oxidative stress, and apoptosis. In the H 2 (-) group, IRI was indicated by a higher aspartate aminotransferase (AST), alanine aminotransferase (ALT) leakage, portal resistance, 8-hydroxy-2-deoxyguanosine-positive cell rate, apoptotic index, and endothelial endothelin-1 expression, together with reduced bile production, oxygen consumption, and GSH/GSSG ratio (vs. CT). In the H 2 (+) group, these harmful changes were significantly suppressed [vs. H 2 (-)]. Hydrogen gas reduced hepatic reperfusion injury after prolonged cold preservation via the maintenance of portal flow, by protecting mitochondrial function during the early phase of reperfusion, and via the suppression of oxidative stress and inflammatory cascades thereafter. Copyright © 2016 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Effect of copper sulphate on the rate of afferent discharge in the gastric branch of the vagus nerve in the rat

NASA Technical Reports Server (NTRS)

Niijima, Akira; Jiang, Zheng-Yao; Daunton, Nancy G.; Fox, Robert A.

1991-01-01

The afferent nerve activity was recorded from a nerve filament isolated from the peripheral cut end of the gastric branch of the vagus nerve. The gastric perfusion of 4 ml of two different concentrations (0.04 percent and 0.08 percent) of CuSO4 solution provoked an increase in afferent activity. The stimulating effect of the 0.08 percent solution was stronger than that of the 0.04 percent solution, and lasted for a longer period of time. The observations suggest a possible mechanism by which CuSO4 elicits emesis.

Evaluation of a high framerate multi-exposure laser speckle contrast imaging setup

NASA Astrophysics Data System (ADS)

Hultman, Martin; Fredriksson, Ingemar; Strömberg, Tomas; Larsson, Marcus

2018-02-01

We present a first evaluation of a new multi-exposure laser speckle contrast imaging (MELSCI) system for assessing spatial variations in the microcirculatory perfusion. The MELSCI system is based on a 1000 frames per second 1-megapixel camera connected to a field programmable gate arrays (FPGA) capable of producing MELSCI data in realtime. The imaging system is evaluated against a single point laser Doppler flowmetry (LDF) system during occlusionrelease provocations of the arm in five subjects. Perfusion is calculated from MELSCI data using current state-of-the-art inverse models. The analysis displayed a good agreement between measured and modeled data, with an average error below 6%. This strongly indicates that the applied model is capable of accurately describing the MELSCI data and that the acquired data is of high quality. Comparing readings from the occlusion-release provocation showed that the MELSCI perfusion was significantly correlated (R=0.83) to the single point LDF perfusion, clearly outperforming perfusion estimations based on a single exposure time. We conclude that the MELSCI system provides blood flow images of enhanced quality, taking us one step closer to a system that accurately can monitor dynamic changes in skin perfusion over a large area in real-time.

Two dose investigation of the 5-HT-agonist psilocybin on relative and global cerebral blood flow.

PubMed

Lewis, Candace R; Preller, Katrin H; Kraehenmann, Rainer; Michels, Lars; Staempfli, Philipp; Vollenweider, Franz X

2017-10-01

Psilocybin, the active compound in psychedelic mushrooms, is an agonist of various serotonin receptors. Seminal psilocybin positron emission tomography (PET) research suggested regional increases in glucose metabolism in frontal cortex (hyperfrontality). However, a recent arterial spin labeling (ASL) study suggests psilocybin may lead to hypo-perfusion in various brain regions. In this placebo-controlled, double-blind study we used pseudo-continuous ASL (pCASL) to measure perfusion changes, with and without adjustment for global brain perfusion, after two doses of oral psilocybin (low dose: 0.160 mg/kg; high dose: 0.215 mg/kg) in two groups of healthy controls (n = 29 in both groups, total N = 58) during rest. We controlled for sex and age and used family-wise error corrected p values in all neuroimaging analyses. Both dose groups reported profound subjective drug effects as measured by the Altered States of Consciousness Rating Scale (5D-ASC) with the high dose inducing significantly larger effects in four out of the 11 scales. After adjusting for global brain perfusion, psilocybin increased relative perfusion in distinct right hemispheric frontal and temporal regions and bilaterally in the anterior insula and decreased perfusion in left hemispheric parietal and temporal cortices and left subcortical regions. Whereas, psilocybin significantly reduced absolute perfusion in frontal, temporal, parietal, and occipital lobes, and bilateral amygdalae, anterior cingulate, insula, striatal regions, and hippocampi. Our analyses demonstrate consistency with both the hyperfrontal hypothesis of psilocybin and the more recent study demonstrating decreased perfusion, depending on analysis method. Importantly, our data illustrate that relative changes in perfusion should be understood and interpreted in relation to absolute signal variations. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

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 to pressure after SCI. PMID:18092567

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.

Can Combined Bypass Surgery at Middle Cerebral Artery Territory Save Anterior Cerebral Artery Territory in Adult Moyamoya Disease?

PubMed

Cho, Won-Sang; Kim, Jeong Eun; Paeng, Jin Chul; Suh, Minseok; Kim, Yong-Il; Kang, Hyun-Seung; Son, Young Je; Bang, Jae Seung; Oh, Chang Wan

2017-03-01

Patients with moyamoya disease are frequently encountered with improved symptoms related to anterior cerebral artery territory (ACAt) and middle cerebral artery territory (MCAt) after bypass surgery at MCAt. To evaluate hemodynamic changes in MCAt and ACAt after bypass surgery in adult moyamoya disease. Combined bypass surgery was performed on 140 hemispheres in 126 patients with MCAt symptoms. Among them, 87 hemispheres (62.1%) accompanied preoperative ACAt symptoms. Clinical, hemodynamic, and angiographic states were evaluated preoperatively and approximately 6 months after surgery. Preoperative symptoms resolved in 127 MCAt (90.7%) and 82 ACAt (94.3%). Hemodynamic analysis of total patients showed a significant improvement in MCAt basal perfusion and reservoir capacity ( P < .001 and P = .002, respectively) and ACAt basal perfusion ( P = .001). In a subgroup analysis, 82 hemispheres that completely recovered from preoperative ACAt symptoms showed a significant improvement in MCAt basal perfusion and reservoir capacity ( P < .001 and P = .05, respectively) and ACAt basal perfusion ( P = .04). Meanwhile, 53 hemispheres that had never experienced ACAt symptoms significantly improved MCAt basal perfusion and reservoir capacity ( P < .001 and P = .05, respectively); however, no ACAt changes were observed. A qualitative angiographic analysis demonstrated a higher trend of leptomeningeal formation from MCAt to ACAt in the former subgroup ( P = .05). During follow-up, no ACAt infarctions were observed. Combined bypass surgery at MCAt resulted in hemodynamic improvements in ACAt and MCAt, especially in patients with preoperative ACAt symptoms. Copyright © 2017 by the Congress of Neurological Surgeons

The fractal heart — embracing mathematics in the cardiology clinic

PubMed Central

Captur, Gabriella; Karperien, Audrey L.; Hughes, Alun D.; Francis, Darrel P.; Moon, James C.

2017-01-01

For clinicians grappling with quantifying the complex spatial and temporal patterns of cardiac structure and function (such as myocardial trabeculae, coronary microvascular anatomy, tissue perfusion, myocyte histology, electrical conduction, heart rate, and blood-pressure variability), fractal analysis is a powerful, but still underused, mathematical tool. In this Perspectives article, we explain some fundamental principles of fractal geometry and place it in a familiar medical setting. We summarize studies in the cardiovascular sciences in which fractal methods have successfully been used to investigate disease mechanisms, and suggest potential future clinical roles in cardiac imaging and time series measurements. We believe that clinical researchers can deploy innovative fractal solutions to common cardiac problems that might ultimately translate into advancements for patient care. PMID:27708281

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 then clearance of viscous fluid within the cochlea, or to a temporary position shift of the Organ of Corti. After 0.5% HA perfusion, a short latency positive peak (P0) appeared in the CAP waveform. This P0 might be due to a change in the cochlea's traveling-wave pattern, or distortion in the cochlear microphonic. Copyright © 2016 Elsevier B.V. All rights reserved.

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, perhaps due to the presence and then clearance of viscous fluid within the cochlea, or to a temporary position shift of the Organ of Corti. After 0.5% HA perfusion, a short latency positive peak (P0) appeared in the CAP wavefrom. This P0 might be due to a change in the cochlea’s traveling-wave pattern, or distortion in the cochlear microphonic. PMID:27220484

A microvascular compartment model validated using 11C-methylglucose liver PET in pigs

NASA Astrophysics Data System (ADS)

Munk, Ole L.; Keiding, Susanne; Baker, Charles; Bass, Ludvik

2018-01-01

The standard compartment model (CM) is widely used to analyse dynamic PET data. The CM is fitted to time-activity curves to estimate rate constants that describe the transport of a tracer between well-mixed compartments. The aim of this study was to develop and validate a more realistic microvascular compartment model (MCM) that includes capillary tracer concentration gradients, backflux from cells into the perfused capillaries and multiple re-uptakes during the passage through a capillary. The MCM incorporates only parameters with clear physiological meaning, it is easy to implement, and it does not require numerical solution. We compared the MCM and CM for the analysis of 3 min dynamic PET data of pig livers (N  =  5) following injection of 11C-methylglucose. During PET scans, the tracer concentrations in blood were measured in the abdominal aorta, portal vein and liver vein by manual sampling. We found that the MCM outperformed the CM and that dynamic PET data include information which cannot be extracted using standard CM. The MCM fitted dynamic PET data better than the CM (Akaike values were 46  ±  4 for best MCM fits, and 82  ±  8 for best CM fits; mean  ±  standard deviation) and extracted physiologically reasonable parameter estimates such as blood perfusion that were in agreement with independent measurements. The difference between model-independent perfusion estimates and the best MCM perfusion estimates was  -0.01  ±  0.05 ml/ml/min, whereas the difference was 0.30  ±  0.13 ml/ml/min using the CM. In addition, the MCM predicted the time course of concentrations in the liver vein, a prediction fundamentally unobtainable using the CM as it does not return tracer backflux from cells to capillary blood. The results demonstrate the benefit of using models that include more physiology and that models including concentration gradients should be preferred when analysing the blood-cell exchange of any tracer in any capillary bed.

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.

SU-C-201-04: Quantification of Perfusion Heterogeneity Based On Texture Analysis for Fully Automatic Detection of Ischemic Deficits From Myocardial Perfusion Imaging

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

Fang, Y; Huang, H; Su, T

Purpose: Texture-based quantification of image heterogeneity has been a popular topic for imaging studies in recent years. As previous studies mainly focus on oncological applications, we report our recent efforts of applying such techniques on cardiac perfusion imaging. A fully automated procedure has been developed to perform texture analysis for measuring the image heterogeneity. Clinical data were used to evaluate the preliminary performance of such methods. Methods: Myocardial perfusion images of Thallium-201 scans were collected from 293 patients with suspected coronary artery disease. Each subject underwent a Tl-201 scan and a percutaneous coronary intervention (PCI) within three months. The PCImore » Result was used as the gold standard of coronary ischemia of more than 70% stenosis. Each Tl-201 scan was spatially normalized to an image template for fully automatic segmentation of the LV. The segmented voxel intensities were then carried into the texture analysis with our open-source software Chang Gung Image Texture Analysis toolbox (CGITA). To evaluate the clinical performance of the image heterogeneity for detecting the coronary stenosis, receiver operating characteristic (ROC) analysis was used to compute the overall accuracy, sensitivity and specificity as well as the area under curve (AUC). Those indices were compared to those obtained from the commercially available semi-automatic software QPS. Results: With the fully automatic procedure to quantify heterogeneity from Tl-201 scans, we were able to achieve a good discrimination with good accuracy (74%), sensitivity (73%), specificity (77%) and AUC of 0.82. Such performance is similar to those obtained from the semi-automatic QPS software that gives a sensitivity of 71% and specificity of 77%. Conclusion: Based on fully automatic procedures of data processing, our preliminary data indicate that the image heterogeneity of myocardial perfusion imaging can provide useful information for automatic determination of the myocardial ischemia.« less

Acidification of rabbit corneal endothelium during contact lens wear in vitro.

PubMed

Giasson, C; Bonanno, J A

1995-04-01

Contact lens wear causes significant epithelial and stromal acidosis. In this study, we tested whether lens wear can cause endothelial acidosis as well. Rabbit corneas were isolated and perfused in vitro. The endothelial intracellular pH (pHi) was measured with a pH sensitive fluorescent probe (BCECF). Three conditions were examined: 1) Polymethylmethacrylate (PMMA) and rigid gas-permeable (RGP) contact lens wear using a range of oxygen transmissibility (Dk/L) from 0 to 121, 2) epithelial hypoxia produced by exposure to oligomycin/sodium azide solution or epithelial perfusion with 100% N2 equilibrated Ringer's solution, and 3) epithelial exposure to Ringer's equilibrated with 5% CO2, balance air. PMMA and RGP contact lens wear acidified endothelial cells by 0.23 +/- 0.01 (n = 23) and 0.11 +/- 0.01 pH units (n = 23), respectively, within twenty min of lens insertion. Epithelial hypoxia, induced by sodium azide and oligomycin, reversibly acidified the endothelium by 0.04 +/- 0.01 pH units (n = 4). However, epithelial hypoxia induced by perfusion with 100% N2 equilibrated Ringer's did not have a significant effect on endothelial pHi. Introduction of 5% CO2 to the epithelium, acidified the endothelium by 0.15 +/- 0.02 pH units (n = 7) within 10 min. We conclude that contact lens wear can significantly acidify corneal endothelial cells. The endothelial pHi change is caused almost exclusively by a build up of CO2 behind the lens; hypoxia having very little contribution. As expected, RGP contact lenses induced less endothelial acidosis than PMMA controls.

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

PubMed

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

2013-01-01

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

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.

The Ethanol-Induced Stimulation of Rat Duodenal Mucosal Bicarbonate Secretion In Vivo Is Critically Dependent on Luminal Cl–

PubMed Central

Sommansson, Anna; Wan Saudi, Wan Salman; Nylander, Olof; Sjöblom, Markus

2014-01-01

Alcohol may induce metabolic and functional changes in gastrointestinal epithelial cells, contributing to impaired mucosal barrier function. Duodenal mucosal bicarbonate secretion (DBS) is a primary epithelial defense against gastric acid and also has an important function in maintaining the homeostasis of the juxtamucosal microenvironment. The aim in this study was to investigate the effects of the luminal perfusion of moderate concentrations of ethanol in vivo on epithelial DBS, fluid secretion and paracellular permeability. Under thiobarbiturate anesthesia, a ∼30-mm segment of the proximal duodenum with an intact blood supply was perfused in situ in rats. The effects on DBS, duodenal transepithelial net fluid flux and the blood-to-lumen clearance of 51Cr-EDTA were investigated. Perfusing the duodenum with isotonic solutions of 10% or 15% ethanol-by-volume for 30 min increased DBS in a concentration-dependent manner, while the net fluid flux did not change. Pre-treatment with the CFTR inhibitor CFTRinh172 (i.p. or i.v.) did not change the secretory response to ethanol, while removing Cl− from the luminal perfusate abolished the ethanol-induced increase in DBS. The administration of hexamethonium (i.v.) but not capsazepine significantly reduced the basal net fluid flux and the ethanol-induced increase in DBS. Perfusing the duodenum with a combination of 1.0 mM HCl and 15% ethanol induced significantly greater increases in DBS than 15% ethanol or 1.0 mM HCl alone but did not influence fluid flux. Our data demonstrate that ethanol induces increases in DBS through a mechanism that is critically dependent on luminal Cl− and partly dependent on enteric neural pathways involving nicotinic receptors. Ethanol and HCl appears to stimulate DBS via the activation of different bicarbonate transporting mechanisms. PMID:25033198

Hemofiltration in ex vivo lung perfusion-a study in experimentally induced pulmonary edema.

PubMed

Nilsson, Tobias; Hansson, Christoffer; Wallinder, Andreas; Malm, Carl-Johan; Silverborn, Martin; Ricksten, Sven-Erik; Dellgren, Göran

2016-02-01

Ex vivo lung perfusion (EVLP) can potentially reduce pulmonary edema. In a pig model with induced pulmonary edema, we evaluated the effect of hemofiltration (HF) during EVLP on lung function, perfusate oncotic pressure, and lung weight. In anesthetized pigs (n = 14), pulmonary edema was induced by a balloon in the left atrium, combined with crystalloid infusion (20 mL/kg), for 2 hours. The lungs were harvested, stored cold for 2 hours, and randomized to EVLP, with or without a hemofilter (HF and noHF groups, respectively, n = 7 for each). EVLP was performed with cellular perfusate at a hematocrit of 10% to 15%. Oncotic pressure, lung performance, and weight were measured before and after 180 minutes of EVLP reconditioning with or without HF. After in vivo induction of edema, arterial oxygen tension (Pao2)/inspired oxygen fraction (Fio2), and compliance decreased by 63% and 16%, respectively. Pao2/Fio2 was considerably improved at first evaluation ex vivo in both groups. HF increased oncotic pressure by 43% and decreased lung weight by 15%. The effects were negligible in the noHF group. Compliance decreased in both groups during reconditioning, although less so in the HF group (P < .05). Pao2/Fio2, shunt fraction, and oxygen saturation remained unchanged in both groups. Pulmonary flow index decreased in both groups, and was partially reversed by nitroglycerin. Dorsal atelectatic consolidations were seen in both groups. In this lung-edema model, EVLP reconditioning with hyperoncotic solution did not affect the degree of lung edema. HF during EVLP increased perfusate oncotic pressure, decreased lung weight with beneficial effects on compliance, but did not improve lung oxygenation capacity. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Corrections of arterial input function for dynamic H215O PET to assess perfusion of pelvic tumours: arterial blood sampling versus image extraction

NASA Astrophysics Data System (ADS)

Lüdemann, L.; Sreenivasa, G.; Michel, R.; Rosner, C.; Plotkin, M.; Felix, R.; Wust, P.; Amthauer, H.

2006-06-01

Assessment of perfusion with 15O-labelled water (H215O) requires measurement of the arterial input function (AIF). The arterial time activity curve (TAC) measured using the peripheral sampling scheme requires corrections for delay and dispersion. In this study, parametrizations with and without arterial spillover correction for fitting of the tissue curve are evaluated. Additionally, a completely noninvasive method for generation of the AIF from a dynamic positron emission tomography (PET) acquisition is applied to assess perfusion of pelvic tumours. This method uses a volume of interest (VOI) to extract the TAC from the femoral artery. The VOI TAC is corrected for spillover using a separate tissue TAC and for recovery by determining the recovery coefficient on a coregistered CT data set. The techniques were applied in five patients with pelvic tumours who underwent a total of 11 examinations. Delay and dispersion correction of the blood TAC without arterial spillover correction yielded in seven examinations solutions inconsistent with physiology. Correction of arterial spillover increased the fitting accuracy and yielded consistent results in all patients. Generation of an AIF from PET image data was investigated as an alternative to arterial blood sampling and was shown to have an intrinsic potential to determine the AIF noninvasively and reproducibly. The AIF extracted from a VOI in a dynamic PET scan was similar in shape to the blood AIF but yielded significantly higher tissue perfusion values (mean of 104.0 ± 52.0%) and lower partition coefficients (-31.6 ± 24.2%). The perfusion values and partition coefficients determined with the VOI technique have to be corrected in order to compare the results with those of studies using a blood AIF.

The ethanol-induced stimulation of rat duodenal mucosal bicarbonate secretion in vivo is critically dependent on luminal Cl-.

PubMed

Sommansson, Anna; Wan Saudi, Wan Salman; Nylander, Olof; Sjöblom, Markus

2014-01-01

Alcohol may induce metabolic and functional changes in gastrointestinal epithelial cells, contributing to impaired mucosal barrier function. Duodenal mucosal bicarbonate secretion (DBS) is a primary epithelial defense against gastric acid and also has an important function in maintaining the homeostasis of the juxtamucosal microenvironment. The aim in this study was to investigate the effects of the luminal perfusion of moderate concentrations of ethanol in vivo on epithelial DBS, fluid secretion and paracellular permeability. Under thiobarbiturate anesthesia, a ∼30-mm segment of the proximal duodenum with an intact blood supply was perfused in situ in rats. The effects on DBS, duodenal transepithelial net fluid flux and the blood-to-lumen clearance of 51Cr-EDTA were investigated. Perfusing the duodenum with isotonic solutions of 10% or 15% ethanol-by-volume for 30 min increased DBS in a concentration-dependent manner, while the net fluid flux did not change. Pre-treatment with the CFTR inhibitor CFTRinh172 (i.p. or i.v.) did not change the secretory response to ethanol, while removing Cl- from the luminal perfusate abolished the ethanol-induced increase in DBS. The administration of hexamethonium (i.v.) but not capsazepine significantly reduced the basal net fluid flux and the ethanol-induced increase in DBS. Perfusing the duodenum with a combination of 1.0 mM HCl and 15% ethanol induced significantly greater increases in DBS than 15% ethanol or 1.0 mM HCl alone but did not influence fluid flux. Our data demonstrate that ethanol induces increases in DBS through a mechanism that is critically dependent on luminal Cl- and partly dependent on enteric neural pathways involving nicotinic receptors. Ethanol and HCl appears to stimulate DBS via the activation of different bicarbonate transporting mechanisms.

In vivo evaluation of acid-induced changes in oesophageal mucosa integrity and sensitivity in non-erosive reflux disease.

PubMed

Woodland, Philip; Al-Zinaty, Mohannad; Yazaki, Etsuro; Sifrim, Daniel

2013-09-01

Patients with non-erosive reflux disease (NERD) have impaired oesophageal mucosal integrity (dilated intercellular spaces). Oesophageal mucosal integrity reflects the balance between repeated reflux damage and mucosal recovery. The relationship between mucosal integrity and acid sensitivity is unclear. Oesophageal impedance may be used for in vivo mucosal integrity measurement. We studied acid-induced changes in oesophageal mucosal integrity and acid perception in patients with heartburn. 50 patients with heartburn whithout oesophagitis underwent impedance monitoring before, during and after 10 min oesophageal perfusion with neutral (pH 6.5) and acid solutions (pH 1). Symptoms and impedance were recorded during perfusion. Impedance recovery was assessed for 2 h post-perfusion in ambulatory conditions followed by 24-h impedance-pH study. Reflux monitoring discriminated 20 NERD and 30 functional heartburn (FH) patients. Neutral perfusion caused impedance fall that recovered within 10 min. Acid perfusion caused impedance fall with slow recovery: 6.5 Ω/min (IQR 3.3-12.0 Ω/min). Patients with slow recovery (< 25th percentile) had lower baseline impedance (1273 Ω ± 208 Ω vs. 3220 Ω ± 275 Ω ±, p < 0.01) and more frequent acid sensitivity (10/12 vs. 4/12, p = 0.04) than those with fast (> 75th percentile) recovery. Patients with NERD had lower baseline impedance (1669 ± 182 Ω vs. 2384 ± 211 Ω, p = 0.02) and slower impedance recovery (6.0 ± 0.9 Ω/min vs. 10.7 ± 1.6 Ω/min, p = 0.03) than patients with FH. Impaired mucosal integrity might be the consequence of repeated reflux episodes with slow recovery. Mucosal integrity, recovery capacity and symptom perception are linked. Low basal impedance and slow recovery after acid challenge are associated with increased acid sensitivity.

Effect of sodium chloride gradients on water flux in rat descending vasa recta.

PubMed

Pallone, T L

1991-01-01

In the hydropenic kidney, volume efflux from descending vasa recta (DVR) occurs despite an intracapillary oncotic pressure that exceeds hydraulic pressure. That finding has been attributed to small solute gradients which may provide an additional osmotic driving force favoring water transport from DVR plasma to the papillary interstitium. To test this hypothesis, axial gradients of NaCl and urea in the papilla were eliminated by administration of furosemide and saline. DVR were then blocked with paraffin and microperfused at 10 nl/min with a buffer containing albumin, fluorescein isothiocyanate labeled dextran (FITC-Dx), 22Na, and NaCl in a concentration of 0 (hypotonic to the interstitium), 161 (isotonic) or 322 mM (hypertonic). Collectate was obtained from the perfused DVR by micropuncture and the collectate-to-perfusate ratios of FITC-Dx and 22Na were measured. A mathematical model was employed to determine DVR permeability (Ps) and reflection coefficient to NaCl (sigma NaCl). The rate of transport of water from the DVR lumen to the papillary interstitium was 2.8 +/- 0.3 (Nv = 22), -0.19 +/- 0.4 (Nv = 15), and -2.3 +/- 0.3 nl/min (Nv = 21) (mean +/- SE) when perfusate NaCl was 0, 161, or 322 mM, respectively (Nv = number of DVR perfused). The collectate-to-perfusate 22Na concentration ratios were 0.34 +/- 0.04, 0.36 +/- 0.04 and 0.37 +/- 0.03 for those groups, respectively. Based on these data, Ps is calculated to be 60.4 x 10(-5) +/- 4.0 x 10(-5) cm/s and sigma NaCl less than 0.05. The results of this study confirm that transcapillary NaCl concentrations gradients induce water movement across the wall of the DVR.

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

PubMed

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

2018-01-01

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

SU-E-QI-06: Design and Initial Validation of a Precise Capillary Phantom to Test Perfusion Systems

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

Wood, R; Iacobucci, G; Khobragade, P

2014-06-15

Purpose: To design a precise perfusion phantom mimicking capillaries of the brain vasculature which could be used to test various perfusion protocols and algorithms which generate perfusion maps. Methods: A perfusion phantom was designed in Solidworks and built using additive manufacturing. The phantom was an overall cylindrical shape of diameter and height 20mm and containing capillaries of 200μm or 300μm which were parallel and in contact making up the inside volume where flow was allowed. We created a flow loop using a peristaltic pump and contrast agent was injected manually. Digital Subtraction Angiographic images and low contrast images with conemore » beam CT were acquired after the contrast was injected. These images were analyzed by our own code in LabVIEW software and Time-Density Curve, MTT and TTP was calculated. Results: Perfused area was visible in the cone beam CT images; however, individual capillaries were not distinguishable. The Time-Density Curve acquired was accurate, sensitive and repeatable. The parameters MTT, and TTP offered by the phantom were very sensitive to slight changes in the TDC shape. Conclusion: We have created a robust calibrating model for evaluation of existing perfusion data analysis systems. This approach is extremely sensitive to changes in the flow due to the high temporal resolution and could be used as a golden standard to assist developers in calibrating and testing of imaging perfusion systems and software algorithms. Supported by NIH Grant: 2R01EB002873 and an equipment grant from Toshiba Medical Systems Corporation.« less

Neurotrophic Substances and Behavioral Recovery from Brain Damage.

DTIC Science & Technology

1983-07-01

intracerebral administration of this substance can increase choline acetyltransferase, an enzyme necessary for the production of neurotransmitter. This...from limbic system 1 Hefti, F., Dravid, A. and Hartikka, J. Chronic intraventricular injections of nerve growth factor elevate hippocampal choline ...testing, the animals were killed with an overdose of anesthetic (Nembutal) and perfused intracardially with saline-formalin solution. Their brains

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.

Myocardial perfusion magnetic resonance imaging using sliding-window conjugate-gradient highly constrained back-projection reconstruction for detection of coronary artery disease.

PubMed

Ma, Heng; Yang, Jun; Liu, Jing; Ge, Lan; An, Jing; Tang, Qing; Li, Han; Zhang, Yu; Chen, David; Wang, Yong; Liu, Jiabin; Liang, Zhigang; Lin, Kai; Jin, Lixin; Bi, Xiaoming; Li, Kuncheng; Li, Debiao

2012-04-15

Myocardial perfusion magnetic resonance imaging (MRI) with sliding-window conjugate-gradient highly constrained back-projection reconstruction (SW-CG-HYPR) allows whole left ventricular coverage, improved temporal and spatial resolution and signal/noise ratio, and reduced cardiac motion-related image artifacts. The accuracy of this technique for detecting coronary artery disease (CAD) has not been determined in a large number of patients. We prospectively evaluated the diagnostic performance of myocardial perfusion MRI with SW-CG-HYPR in patients with suspected CAD. A total of 50 consecutive patients who were scheduled for coronary angiography with suspected CAD underwent myocardial perfusion MRI with SW-CG-HYPR at 3.0 T. The perfusion defects were interpreted qualitatively by 2 blinded observers and were correlated with x-ray angiographic stenoses ≥50%. The prevalence of CAD was 56%. In the per-patient analysis, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of SW-CG-HYPR was 96% (95% confidence interval 82% to 100%), 82% (95% confidence interval 60% to 95%), 87% (95% confidence interval 70% to 96%), 95% (95% confidence interval 74% to100%), and 90% (95% confidence interval 82% to 98%), respectively. In the per-vessel analysis, the corresponding values were 98% (95% confidence interval 91% to 100%), 89% (95% confidence interval 80% to 94%), 86% (95% confidence interval 76% to 93%), 99% (95% confidence interval 93% to 100%), and 93% (95% confidence interval 89% to 97%), respectively. In conclusion, myocardial perfusion MRI using SW-CG-HYPR allows whole left ventricular coverage and high resolution and has high diagnostic accuracy in patients with suspected CAD. Copyright © 2012 Elsevier Inc. All rights reserved.

Laser Doppler imaging of cutaneous blood flow through transparent face masks: a necessary preamble to computer-controlled rapid prototyping fabrication with submillimeter precision.

PubMed

Allely, Rebekah R; Van-Buendia, Lan B; Jeng, James C; White, Patricia; Wu, Jingshu; Niszczak, Jonathan; Jordan, Marion H

2008-01-01

A paradigm shift in management of postburn facial scarring is lurking "just beneath the waves" with the widespread availability of two recent technologies: precise three-dimensional scanning/digitizing of complex surfaces and computer-controlled rapid prototyping three-dimensional "printers". Laser Doppler imaging may be the sensible method to track the scar hyperemia that should form the basis of assessing progress and directing incremental changes in the digitized topographical face mask "prescription". The purpose of this study was to establish feasibility of detecting perfusion through transparent face masks using the Laser Doppler Imaging scanner. Laser Doppler images of perfusion were obtained at multiple facial regions on five uninjured staff members. Images were obtained without a mask, followed by images with a loose fitting mask with and without a silicone liner, and then with a tight fitting mask with and without a silicone liner. Right and left oblique images, in addition to the frontal images, were used to overcome unobtainable measurements at the extremes of face mask curvature. General linear model, mixed model, and t tests were used for data analysis. Three hundred seventy-five measurements were used for analysis, with a mean perfusion unit of 299 and pixel validity of 97%. The effect of face mask pressure with and without the silicone liner was readily quantified with significant changes in mean cutaneous blood flow (P < .5). High valid pixel rate laser Doppler imager flow data can be obtained through transparent face masks. Perfusion decreases with the application of pressure and with silicone. Every participant measured differently in perfusion units; however, consistent perfusion patterns in the face were observed.

Optimal Adenosine Stress for Maximum Stress Perfusion, Coronary Flow Reserve, and Pixel Distribution of Coronary Flow Capacity by Kolmogorov-Smirnov Analysis.

PubMed

Kitkungvan, Danai; Lai, Dejian; Zhu, Hongjian; Roby, Amanda E; Johnson, Nils P; Steptoe, Derek D; Patel, Monica B; Kirkeeide, Richard; Gould, K Lance

2017-02-01

Different adenosine stress imaging protocols have not been systemically validated for absolute myocardial perfusion and coronary flow reserve (CFR) by positron emission tomography, where submaximal stress precludes assessing physiological severity of coronary artery disease. In 127 volunteers, serial rest-stress positron emission tomography scans using rubidium-82 with various adenosine infusion protocols identified (1) the protocol with maximum stress perfusion and CFR, (2) test-retest precision in same subject, (3) stress perfusion and CFR after adenosine compared with dipyridamole, (4) heterogeneity of coronary flow capacity combining stress perfusion and CFR, and (5) potential relevance for patients with risk factors or coronary artery disease. The adenosine 6-minute infusion with rubidium-82 injection at 3 minutes caused CFR that was significantly 15.7% higher than the 4-minute adenosine infusion with rubidium-82 injection at 2 minutes and significantly more homogeneous by Kolmogorov-Smirnov analysis for histograms of 1344 pixel range of perfusion in paired positron emission tomographies. In a coronary artery disease cohort separate from volunteers of this study, compared with the 3/6-minute protocol, the 2/4-minute adenosine protocol would potentially have changed 332 of 1732 (19%) positron emission tomographies at low-risk physiological severity CFR ≥2.3 to CFR <2.0, thereby implying high-risk quantitative severity potentially appropriate for interventions but because of suboptimal stress of the 2/4 protocol in some patients. The 6-minute adenosine infusion with rubidium-82 activation at 3 minutes produced CFR that averaged 15.7% higher than that in the 2/4-minute protocol, thereby potentially providing essential information for personalized management in some patients. © 2017 American Heart Association, Inc.

Retrograde and antegrade cerebral perfusion: results in short elective arch reconstructive times.

PubMed

Milewski, Rita Karianna; Pacini, Davide; Moser, G William; Moeller, Patrick; Cowie, Doreen; Szeto, Wilson Y; Woo, Y Joseph; Desai, Nimesh; Di Marco, Luca; Pochettino, Alberto; Di Bartolomeo, Roberto; Bavaria, Joseph E

2010-05-01

Debate remains regarding optimal cerebral circulatory management during relatively noncomplex, short arch reconstructive times. Both retrograde cerebral perfusion with deep hypothermic circulatory arrest (RCP/DHCA) and antegrade cerebral perfusion with moderate hypothermic circulatory arrest (ACP/MHCA) have emerged as established techniques. The aim of the study was to evaluate perioperative outcomes between antegrade and retrograde cerebral perfusion techniques for elective arch reconstruction times less than 45 minutes. Between 1997 and September 2008, 776 cases from two institutions were reviewed to compare RCP/DHCA and ACP/MHCA perfusion techniques. At the University of Pennsylvania, 682 were treated utilizing RCP/DHCA cerebral protection. At the University of Bologna, 94 were treated with ACP/MHCA and bilateral cerebral perfusion. Mean cerebral ischemic time and visceral ischemic time differed between RCP/DHCA and ACP/MHCA (p < 0.001). Multivariate analysis showed age more than 65 years, atherosclerotic aneurysm, and cross-clamp time as predictors of the composite endpoint of mortality, neurologic event, and acute myocardial infarction. There was no significant difference in permanent neurologic deficit, temporary neurologic dysfunction, or renal failure, between RCP/DHCA and ACP/MHCA. Mortality was comparable across both techniques. Both RCP/DHCA and ACP/MHCA have emerged as effective techniques for selected aortic arch operations with low morbidity and mortality. Univariate analysis revealed no statistically significant differences in primary or secondary outcomes between techniques for aortic reconstruction times less than 45 minutes. Data from this study demonstrate that selective use of either RCP/DHCA or ACP/MHCA provides excellent cerebral and visceral outcomes for elective open aortic surgery with short arch reconstructive times. Copyright (c) 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

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

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

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

1986-03-01

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

Perfusion deficits and functional connectivity alterations in patients with post-traumatic stress disorder

NASA Astrophysics Data System (ADS)

Liu, Yang; Li, Baojuan; Zhang, Xi; Zhang, Linchuan; Li, Liang; Lu, Hongbing

2016-03-01

To explore the alteration in cerebral blood flow (CBF) and functional connectivity between survivors with recent onset post-traumatic stress disorder (PTSD) and without PTSD, survived from the same coal mine flood disaster. In this study, a processing pipeline using arterial spin labeling (ASL) sequence was proposed. Considering low spatial resolution of ASL sequence, a linear regression method was firstly used to correct the partial volume (PV) effect for better CBF estimation. Then the alterations of CBF between two groups were analyzed using both uncorrected and PV-corrected CBF maps. Based on altered CBF regions detected from the CBF analysis as seed regions, the functional connectivity abnormities in PTSD patients was investigated. The CBF analysis using PV-corrected maps indicates CBF deficits in the bilateral frontal lobe, right superior frontal gyrus and right corpus callosum of PTSD patients, while only right corpus callosum was identified in uncorrected CBF analysis. Furthermore, the regional CBF of the right superior frontal gyrus exhibits significantly negative correlation with the symptom severity in PTSD patients. The resting-state functional connectivity indicates increased connectivity between left frontal lobe and right parietal lobe. These results indicate that PV-corrected CBF exhibits more subtle perfusion changes and may benefit further perfusion and connectivity analysis. The symptom-specific perfusion deficits and aberrant connectivity in above memory-related regions may be putative biomarkers for recent onset PTSD induced by a single prolonged trauma exposure and help predict the severity of PTSD.

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.

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

PubMed

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

2008-02-01

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

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

PubMed

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

1997-09-01

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

Pulmonary blood flow distribution in sheep: effects of anesthesia, mechanical ventilation, and change in posture

NASA Technical Reports Server (NTRS)

Walther, S. M.; Domino, K. B.; Glenny, R. W.; Hlastala, M. P.

1997-01-01

BACKGROUND: Recent studies providing high-resolution images of pulmonary perfusion have questioned the classical zone model of pulmonary perfusion. Hence the present work was undertaken to provide detailed maps of regional pulmonary perfusion to examine the influence of anesthesia, mechanical ventilation, and posture. METHODS: Pulmonary perfusion was analyzed with intravenous fluorescent microspheres (15 microm) in six sheep studied in four conditions: prone and awake, prone with pentobarbital-anesthesia and breathing spontaneously, prone with anesthesia and mechanical ventilation, and supine with anesthesia and mechanical ventilation. Lungs were air dried at total lung capacity and sectioned into approximately 1,100 pieces (about 2 cm3) per animal. The pieces were weighed and assigned spatial coordinates. Fluorescence was read on a spectrophotometer, and signals were corrected for piece weight and normalized to mean flow. Pulmonary blood flow heterogeneity was assessed using the coefficient of variation of flow data. RESULTS: Pentobarbital anesthesia and mechanical ventilation did not influence perfusion heterogeneity, but heterogeneity increased when the animals were in the supine posture (P < 0.01). Gravitational flow gradients were absent in the prone position but present in the supine (P < 0.001 compared with zero). Pulmonary perfusion was distributed with a hilar-to-peripheral gradient in animals breathing spontaneously (P < 0.05). CONCLUSIONS: The influence of pentobarbital anesthesia and mechanical ventilation on pulmonary perfusion heterogeneity is small compared with the effect of changes in posture. Analysis of flow gradients indicate that gravity plays a small role in determining pulmonary blood flow distribution.

Effects of Stirring and Fluid Perfusion on the In Vitro Degradation of Calcium Phosphate Cement/PLGA Composites.

PubMed

An, Jie; Leeuwenburgh, Sander C G; Wolke, Joop G C; Jansen, John A

2015-11-01

In vitro degradation rates of calcium phosphate bioceramics are investigated using a large variation of soaking protocols that do not all match the dynamic conditions of the perfused physiological environment. Therefore, we studied the effect of stirring and fluid perfusion on the in vitro degradation rate of apatitic calcium phosphate cements (CPC) containing poly(lactic-co-glycolic acid) (PLGA) microspheres. The composites were soaked in phosphate-buffered saline up to 6 weeks under unstirred, stirred, or perfused conditions followed by analysis of mass loss, compression strength, porosity, crystal phase composition, and morphology of the cement composites. The results showed that fluid perfusion reduced the decrease in pH and corresponding degradation rates, while nonperfused soaking conditions (i.e., stirred and unstirred conditions) resulted into more extensive acidification, the rate of which increased with stirring. After 2 weeks, the formation of a secondary brushite phase was observed for cement composites soaked under nonperfused (i.e., stirred and unstirred) conditions, whereas this phase was not detected in cements soaked under perfused conditions. The degradation rate of cement composites decreased in the order unstirred>stirred>perfused, as evidenced by quantification of mass loss, compression strength, and pore morphology. To summarize, we have demonstrated that soaking conditions strongly affected the in vitro degradation process of CPCs. As a consequence, it can be concluded that the experimental design of current in vitro degradation studies does not allow for correlation to (pre-)clinical studies.

Normal values and standardization of parameters in nuclear cardiology: Japanese Society of Nuclear Medicine working group database.

PubMed

Nakajima, Kenichi; Matsumoto, Naoya; Kasai, Tokuo; Matsuo, Shinro; Kiso, Keisuke; Okuda, Koichi

2016-04-01

As a 2-year project of the Japanese Society of Nuclear Medicine working group activity, normal myocardial imaging databases were accumulated and summarized. Stress-rest with gated and non-gated image sets were accumulated for myocardial perfusion imaging and could be used for perfusion defect scoring and normal left ventricular (LV) function analysis. For single-photon emission computed tomography (SPECT) with multi-focal collimator design, databases of supine and prone positions and computed tomography (CT)-based attenuation correction were created. The CT-based correction provided similar perfusion patterns between genders. In phase analysis of gated myocardial perfusion SPECT, a new approach for analyzing dyssynchrony, normal ranges of parameters for phase bandwidth, standard deviation and entropy were determined in four software programs. Although the results were not interchangeable, dependency on gender, ejection fraction and volumes were common characteristics of these parameters. Standardization of (123)I-MIBG sympathetic imaging was performed regarding heart-to-mediastinum ratio (HMR) using a calibration phantom method. The HMRs from any collimator types could be converted to the value with medium-energy comparable collimators. Appropriate quantification based on common normal databases and standard technology could play a pivotal role for clinical practice and researches.

Colloids and the Microcirculation.

PubMed

He, Huaiwu; Liu, Dawei; Ince, Can

2018-05-01

Colloid solutions have been advocated for use in treating hypovolemia due to their expected effect on improving intravascular retention compared with crystalloid solutions. Because the ultimate desired effect of fluid resuscitation is the improvement of microcirculatory perfusion and tissue oxygenation, it is of interest to study the effects of colloids and crystalloids at the level of microcirculation under conditions of shock and fluid resuscitation, and to explore the potential benefits of using colloids in terms of recruiting the microcirculation under conditions of hypovolemia. This article reviews the physiochemical properties of the various types of colloid solutions (eg, gelatin, dextrans, hydroxyethyl starches, and albumin) and the effects that they have under various conditions of hypovolemia in experimental and clinical scenarios.

A chamber for the perfusion of in vitro tissue with multiple solutions

PubMed Central

Covington, James A.; Wall, Mark J.

2013-01-01

There are currently no practical systems that allow extended regions (>5 mm2) of a tissue slice in vitro to be exposed, in isolation, to changes in ionic conditions or to pharmacological manipulation. Previous work has only achieved this at the expense of access to the tissue for recording electrodes. Here, we present a chamber that allows a tissue slice to be maintained in multiple solutions, at physiological temperatures, and preserves the ability to record from the slice. We demonstrate the effectiveness of the tissue bath with respect to minimizing the mixing of the solutions, maintaining the viability of the tissue, and preserving the ability to record from the slice simultaneously. PMID:23576703

Comparing model-based and model-free analysis methods for QUASAR arterial spin labeling perfusion quantification.

PubMed

Chappell, Michael A; Woolrich, Mark W; Petersen, Esben T; Golay, Xavier; Payne, Stephen J

2013-05-01

Amongst the various implementations of arterial spin labeling MRI methods for quantifying cerebral perfusion, the QUASAR method is unique. By using a combination of labeling with and without flow suppression gradients, the QUASAR method offers the separation of macrovascular and tissue signals. This permits local arterial input functions to be defined and "model-free" analysis, using numerical deconvolution, to be used. However, it remains unclear whether arterial spin labeling data are best treated using model-free or model-based analysis. This work provides a critical comparison of these two approaches for QUASAR arterial spin labeling in the healthy brain. An existing two-component (arterial and tissue) model was extended to the mixed flow suppression scheme of QUASAR to provide an optimal model-based analysis. The model-based analysis was extended to incorporate dispersion of the labeled bolus, generally regarded as the major source of discrepancy between the two analysis approaches. Model-free and model-based analyses were compared for perfusion quantification including absolute measurements, uncertainty estimation, and spatial variation in cerebral blood flow estimates. Major sources of discrepancies between model-free and model-based analysis were attributed to the effects of dispersion and the degree to which the two methods can separate macrovascular and tissue signal. Copyright © 2012 Wiley Periodicals, Inc.

The Ionic Permeability Changes during Acetylcholine-Induced Responses of Aplysia Ganglion Cells

PubMed Central

Sato, Makoto; Austin, George; Yai, Hideko; Maruhashi, Juro

1968-01-01

ACh-induced depolarization (D response) in D cells markedly decreases as the external Na+ is reduced. However, when Na+ is completely replaced with Mg++, the D response remains unchanged. When Na+ is replaced with Tris(hydroxymethyl)aminomethane, the D response completely disappears, except for a slight decrease in membrane resistance. ACh-induced hyperpolarization (H response) in H cells is markedly depressed as the external Cl- is reduced. Frequently, the reversal of the H response; i.e., depolarization, is observed during perfusion with Cl--free media. In cells which show both D and H responses superimposed, it was possible to separate these responses from each other by perfusing the cells with either Na+-free or Cl--free Ringer's solution. High [K+]0 often caused a marked hyperpolarization in either D or H cells. This is due to the primary effect of high [K+]0 on the presynaptic inhibitory fibers. The removal of this inhibitory afferent interference by applying Nembutal readily disclosed the predicted K+ depolarization. In perfusates containing normal [Na+]0, the effects of Ca++ and Mg++ on the activities of postsynaptic membrane were minimal, supporting the current theory that the effects of these ions on the synaptic transmission are mainly presynaptic. The possible mechanism of the hyperpolarization produced by simultaneous perfusion with both high [K+]0 and ACh in certain H cells is explained quantitatively under the assumption that ACh induces exclusively an increase in Cl- permeability of the H membrane. PMID:5648831

Diabetes Diminishes the Portal-Systemic Collateral Vascular Response to Vasopressin via Vasopressin Receptor and Gα Proteins Regulations in Cirrhotic Rats

PubMed Central

Lee, Jing-Yi; Huo, Teh-Ia; Wang, Sun-Sang; Lin, Han-Chieh; Chuang, Chiao-Lin; Lee, Shou-Dong

2013-01-01

Liver cirrhosis may lead to portal-systemic collateral formation and bleeding. The hemostatic effect is influenced by the response of collateral vessels to vasoconstrictors. Diabetes and glucose also influence vasoresponsiveness, but their net effect on collaterals remains unexplored. This study investigated the impact of diabetes or glucose application on portal-systemic collateral vasoresponsiveness to arginine vasopressin (AVP) in cirrhosis. Spraque-Dawley rats with bile duct ligation (BDL)-induced cirrhosis received vehicle (citrate buffer) or streptozotocin (diabetic, BDL/STZ). The in situ collateral perfusion was done after hemodynamic measurements: Both were perfused with Krebs solution, D-glucose, or D-glucose and NaF, with additional OPC-31260 for the BDL/STZ group. Splenorenal shunt vasopressin receptors and Gα proteins mRNA expressions were evaluated. The survival rate of cirrhotic rats was decreased by STZ injection. The collateral perfusion pressure changes to AVP were lower in STZ-injected groups, which were reversed by OPC-31260 (a V2R antagonist) and overcome by NaF (a G protein activator). The splenorenal shunt V2R mRNA expression was increased while Gα proteins mRNA expressions were decreased in BDL/STZ rats compared to BDL rats. The Gαq and Gα11 mRNA expressions also correlated with the maximal perfusion pressure changes to AVP. Diabetes diminished the portal-systemic collateral vascular response to AVP in rats with BDL-induced cirrhosis, probably via V2 receptor up-regulation and Gα proteins down-regulation. PMID:23874439

Diabetes diminishes the portal-systemic collateral vascular response to vasopressin via vasopressin receptor and Gα proteins regulations in cirrhotic rats.

PubMed

Lee, Jing-Yi; Huo, Teh-Ia; Wang, Sun-Sang; Huang, Hui-Chun; Lee, Fa-Yauh; Lin, Han-Chieh; Chuang, Chiao-Lin; Lee, Shou-Dong

2013-01-01

Liver cirrhosis may lead to portal-systemic collateral formation and bleeding. The hemostatic effect is influenced by the response of collateral vessels to vasoconstrictors. Diabetes and glucose also influence vasoresponsiveness, but their net effect on collaterals remains unexplored. This study investigated the impact of diabetes or glucose application on portal-systemic collateral vasoresponsiveness to arginine vasopressin (AVP) in cirrhosis. Spraque-Dawley rats with bile duct ligation (BDL)-induced cirrhosis received vehicle (citrate buffer) or streptozotocin (diabetic, BDL/STZ). The in situ collateral perfusion was done after hemodynamic measurements: Both were perfused with Krebs solution, D-glucose, or D-glucose and NaF, with additional OPC-31260 for the BDL/STZ group. Splenorenal shunt vasopressin receptors and Gα proteins mRNA expressions were evaluated. The survival rate of cirrhotic rats was decreased by STZ injection. The collateral perfusion pressure changes to AVP were lower in STZ-injected groups, which were reversed by OPC-31260 (a V2R antagonist) and overcome by NaF (a G protein activator). The splenorenal shunt V2R mRNA expression was increased while Gα proteins mRNA expressions were decreased in BDL/STZ rats compared to BDL rats. The Gαq and Gα11 mRNA expressions also correlated with the maximal perfusion pressure changes to AVP. Diabetes diminished the portal-systemic collateral vascular response to AVP in rats with BDL-induced cirrhosis, probably via V2 receptor up-regulation and Gα proteins down-regulation.

Microprocessor-based integration of microfluidic control for the implementation of automated sensor monitoring and multithreaded optimization algorithms.

PubMed

Ezra, Elishai; Maor, Idan; Bavli, Danny; Shalom, Itai; Levy, Gahl; Prill, Sebastian; Jaeger, Magnus S; Nahmias, Yaakov

2015-08-01

Microfluidic applications range from combinatorial synthesis to high throughput screening, with platforms integrating analog perfusion components, digitally controlled micro-valves and a range of sensors that demand a variety of communication protocols. Currently, discrete control units are used to regulate and monitor each component, resulting in scattered control interfaces that limit data integration and synchronization. Here, we present a microprocessor-based control unit, utilizing the MS Gadgeteer open framework that integrates all aspects of microfluidics through a high-current electronic circuit that supports and synchronizes digital and analog signals for perfusion components, pressure elements, and arbitrary sensor communication protocols using a plug-and-play interface. The control unit supports an integrated touch screen and TCP/IP interface that provides local and remote control of flow and data acquisition. To establish the ability of our control unit to integrate and synchronize complex microfluidic circuits we developed an equi-pressure combinatorial mixer. We demonstrate the generation of complex perfusion sequences, allowing the automated sampling, washing, and calibrating of an electrochemical lactate sensor continuously monitoring hepatocyte viability following exposure to the pesticide rotenone. Importantly, integration of an optical sensor allowed us to implement automated optimization protocols that require different computational challenges including: prioritized data structures in a genetic algorithm, distributed computational efforts in multiple-hill climbing searches and real-time realization of probabilistic models in simulated annealing. Our system offers a comprehensive solution for establishing optimization protocols and perfusion sequences in complex microfluidic circuits.

Effects of anti-malarial drugs on the electrocardiographic QT interval modelled in the isolated perfused guinea pig heart system

PubMed Central

2010-01-01

Background Concern over the potential cardiotoxicity of anti-malarial drugs inducing a prolonged electrocardiographic QT interval has resulted in the almost complete withdrawal from the market of one anti-malarial drug - halofantrine. The effects on the QT interval of four anti-malarial drugs were examined, using the guinea pig heart. Methods The guinea pig heart was isolated, mounted on a Langendorff apparatus, and was then perfused with pyruvate-added Klebs-Henseleit solutions containing graded concentrations of the four agents such as quinidine (0.15 - 1.2 μM), quinine (0.3 - 2.4 μM), halofantrine (0.1 - 2.0 μM) and mefloquine (0.1 - 2.0 μM). The heart rate-corrected QaTc intervals were measured to evaluate drug-induced QT prolongation effects. Results Quinidine, quinine, and halofantrine prolonged the QaTc interval in a dose-dependent manner, whereas no such effect was found with mefloquine. The EC50 values for the QaTc prolongation effects, the concentration that gives a half-maximum effect, were quinidine < quinine ≈ halofantrine. Conclusions In this study, an isolated, perfused guinea pig heart system was constructed to assess the cardiotoxic potential of anti-malarial drugs. This isolated perfused guinea pig heart system could be used to test newly developed anti-malarial drugs for their inherent QT lengthening potential. More information is required on the potential variation in unbound drug concentrations in humans, and their role in cardiotoxicity. PMID:21067575

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

PubMed

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

2004-11-17

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

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

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.

Cognitive function in patients with stable coronary heart disease: Related cerebrovascular and cardiovascular responses.

PubMed

Gayda, Mathieu; Gremeaux, Vincent; Bherer, Louis; Juneau, Martin; Drigny, Joffrey; Dupuy, Olivier; Lapierre, Gabriel; Labelle, Véronique; Fortier, Annik; Nigam, Anil

2017-01-01

Chronic exercise has been shown to prevent or slow age-related decline in cognitive functions in otherwise healthy, asymptomatic individuals. We sought to assess cognitive function in a stable coronary heart disease (CHD) sample and its relationship to cerebral oxygenation-perfusion, cardiac hemodynamic responses, and [Formula: see text] peak compared to age-matched and young healthy control subjects. Twenty-two young healthy controls (YHC), 20 age-matched old healthy controls (OHC) and 25 patients with stable CHD were recruited. Cognitive function assessment included short term-working memory, perceptual abilities, processing speed, cognitive inhibition and flexibility and long-term verbal memory. Maximal cardiopulmonary function (gas exchange analysis), cardiac hemodynamic (impedance cardiography) and left frontal cerebral oxygenation-perfusion (near-infra red spectroscopy) were measured during and after a maximal incremental ergocycle test. Compared to OHC and CHD, YHC had higher [Formula: see text] peak, maximal cardiac index (CI max), cerebral oxygenation-perfusion (ΔO2 Hb, ΔtHb: exercise and recovery) and cognitive function (for all items) (P<0.05). Compared to OHC, CHD patients had lower [Formula: see text] peak, CI max, cerebral oxygenation-perfusion (during recovery) and short term-working memory, processing speed, cognitive inhibition and flexibility and long-term verbal memory (P<0.05). [Formula: see text] peak and CI max were related to exercise cerebral oxygenation-perfusion and cognitive function (P<0.005). Cerebral oxygenation-perfusion (exercise) was related to cognitive function (P<0.005). Stable CHD patients have a worse cognitive function, a similar cerebral oxygenation/perfusion during exercise but reduced one during recovery vs. their aged-matched healthy counterparts. In the all sample, cognitive functions correlated with [Formula: see text] peak, CI max and cerebral oxygenation-perfusion.

Is liver perfusion CT reproducible? A study on intra- and interobserver agreement of normal hepatic haemodynamic parameters obtained with two different software packages.

PubMed

Bretas, Elisa Almeida Sathler; Torres, Ulysses S; Torres, Lucas Rios; Bekhor, Daniel; Saito Filho, Celso Fernando; Racy, Douglas Jorge; Faggioni, Lorenzo; D'Ippolito, Giuseppe

2017-10-01

To evaluate the agreement between the measurements of perfusion CT parameters in normal livers by using two different software packages. This retrospective study was based on 78 liver perfusion CT examinations acquired for detecting suspected liver metastasis. Patients with any morphological or functional hepatic abnormalities were excluded. The final analysis included 37 patients (59.7 ± 14.9 y). Two readers (1 and 2) independently measured perfusion parameters using different software packages from two major manufacturers (A and B). Arterial perfusion (AP) and portal perfusion (PP) were determined using the dual-input vascular one-compartmental model. Inter-reader agreement for each package and intrareader agreement between both packages were assessed with intraclass correlation coefficients (ICC) and Bland-Altman statistics. Inter-reader agreement was substantial for AP using software A (ICC = 0.82) and B (ICC = 0.85-0.86), fair for PP using software A (ICC = 0.44) and fair to moderate for PP using software B (ICC = 0.56-0.77). Intrareader agreement between software A and B ranged from slight to moderate (ICC = 0.32-0.62) for readers 1 and 2 considering the AP parameters, and from fair to moderate (ICC = 0.40-0.69) for readers 1 and 2 considering the PP parameters. At best there was only moderate agreement between both software packages, resulting in some uncertainty and suboptimal reproducibility. Advances in knowledge: Software-dependent factors may contribute to variance in perfusion measurements, demanding further technical improvements. AP measurements seem to be the most reproducible parameter to be adopted when evaluating liver perfusion CT.

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.

Influence of amplitude-related perfusion parameters in the parotid glands by non-fat-saturated dynamic contrast-enhanced magnetic resonance imaging.

PubMed

Chiu, Su-Chin; Cheng, Cheng-Chieh; Chang, Hing-Chiu; Chung, Hsiao-Wen; Chiu, Hui-Chu; Liu, Yi-Jui; Hsu, Hsian-He; Juan, Chun-Jung

2016-04-01

To verify whether quantification of parotid perfusion is affected by fat signals on non-fat-saturated (NFS) dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and whether the influence of fat is reduced with fat saturation (FS). This study consisted of three parts. First, a retrospective study analyzed DCE-MRI data previously acquired on different patients using NFS (n = 18) or FS (n = 18) scans. Second, a phantom study simulated the signal enhancements in the presence of gadolinium contrast agent at six concentrations and three fat contents. Finally, a prospective study recruited nine healthy volunteers to investigate the influence of fat suppression on perfusion quantification on the same subjects. Parotid perfusion parameters were derived from NFS and FS DCE-MRI data using both pharmacokinetic model analysis and semiquantitative parametric analysis. T tests and linear regression analysis were used for statistical analysis with correction for multiple comparisons. NFS scans showed lower amplitude-related parameters, including parameter A, peak enhancement (PE), and slope than FS scans in the patients (all with P < 0.0167). The relative signal enhancement in the phantoms was proportional to the dose of contrast agent and was lower in NFS scans than in FS scans. The volunteer study showed lower parameter A (6.75 ± 2.38 a.u.), PE (42.12% ± 14.87%), and slope (1.43% ± 0.54% s(-1)) in NFS scans as compared to 17.63 ± 8.56 a.u., 104.22% ± 25.15%, and 9.68% ± 1.67% s(-1), respectively, in FS scans (all with P < 0.005). These amplitude-related parameters were negatively associated with the fat content in NFS scans only (all with P < 0.05). On NFS DCE-MRI, quantification of parotid perfusion is adversely affected by the presence of fat signals for all amplitude-related parameters. The influence could be reduced on FS scans.

Voxel-by-voxel analysis of brain SPECT perfusion in Fibromyalgia

NASA Astrophysics Data System (ADS)

Guedj, Eric; Taïeb, David; Cammilleri, Serge; Lussato, David; de Laforte, Catherine; Niboyet, Jean; Mundler, Olivier

2007-02-01

We evaluated brain perfusion SPECT at rest, without noxious stiumuli, in a homogeneous group of hyperalgesic FM patients. We performed a voxel-based analysis in comparison to a control group, matched for age and gender. Under such conditions, we made the assumption that significant cerebral perfusion abnormalities could be demonstrated, evidencing altered cerebral processing associated with spontaneous pain in FM patients. The secondary objective was to study the reversibility and the prognostic value of such possible perfusion abnormalities under specific treatment. Eighteen hyperalgesic FM women (mean age 48 yr; range 25-63 yr; ACR criteria) and 10 healthy women matched for age were enrolled in the study. A voxel-by-voxel group analysis was performed using SPM2 ( p<0.05, corrected for multiple comparisons). All brain SPECT were performed before any change was made in therapy in the pain care unit. A second SPECT was performed a month later after specific treatment by Ketamine. Compared to control subjects, we observed individual brain SPECT abnormalities in FM patients, confirmed by SPM2 analysis with hyperperfusion of the somatosensory cortex and hypoperfusion of the frontal, cingulate, medial temporal and cerebellar cortices. We also found that a medial frontal and anterior cingulate hypoperfusions were highly predictive (PPV=83%; NPV=91%) of non-response on Ketamine, and that only responders showed significant modification of brain perfusion, after treatment. In the present study performed without noxious stimuli in hyperalgesic FM patients, we found significant hyperperfusion in regions of the brain known to be involved in sensory dimension of pain processing and significant hypoperfusion in areas assumed to be associated with the affective dimension. As current pharmacological and non-pharmacological therapies act differently on both components of pain, we hypothesize that SPECT could be a valuable and readily available tool to guide individual therapeutic strategy and provide objective follow-up of pain-processing recovery under treatment.

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 the overall record keeping for perfusion management. PMID:16524151

Oxygen demand of perfused heart preparations: how electromechanical function and inadequate oxygenation affect physiology and optical measurements.

PubMed

Kuzmiak-Glancy, Sarah; Jaimes, Rafael; Wengrowski, Anastasia M; Kay, Matthew W

2015-06-01

What is the topic of this review? This review discusses how the function and electrophysiology of isolated perfused hearts are affected by oxygenation and energy utilization. The impact of oxygenation on fluorescence measurements in perfused hearts is also discussed. What advances does it highlight? Recent studies have illuminated the inherent differences in electromechanical function, energy utilization rate and oxygen requirements between the primary types of excised heart preparations. A summary and analysis of how these variables affect experimental results are necessary to elevate the physiological relevance of these approaches in order to advance the field of whole-heart research. The ex vivo perfused heart recreates important aspects of in vivo conditions to provide insight into whole-organ function. In this review we discuss multiple types of ex vivo heart preparations, explain how closely each mimic in vivo function, and discuss how changes in electromechanical function and inadequate oxygenation of ex vivo perfused hearts may affect measurements of physiology. Hearts that perform physiological work have high oxygen demand and are likely to experience hypoxia when perfused with a crystalloid perfusate. Adequate myocardial oxygenation is critically important for obtaining physiologically relevant measurements, so when designing experiments the type of ex vivo preparation and the capacity of perfusate to deliver oxygen must be carefully considered. When workload is low, such as during interventions that inhibit contraction, oxygen demand is also low, which could dramatically alter a physiological response to experimental variables. Changes in oxygenation also alter the optical properties of cardiac tissue, an effect that may influence optical signals measured from both endogenous and exogenous fluorophores. Careful consideration of oxygen supply, working condition, and wavelengths used to acquire optical signals is critical for obtaining physiologically relevant measurements during ex vivo perfused heart studies. © 2015 The Authors. Experimental Physiology © 2015 The Physiological Society.

Mechanism of action of honey bee (Apis mellifera L.) venom on different types of muscles.

PubMed

Nabil, Z I; Hussein, A A; Zalat, S M; Rakha, M Kh

1998-03-01

1. The effect of crude honeybee (Apis mellifera) venom on the skeletal, smooth as well as cardiac muscles were studied in this investigation. 2. Perfusion of gastrocnemius-sciatic nerve preparation of frogs with 1 microgram/ml venom solution has weakened the mechanical contraction of the muscle without recovery. Blocking of nicotinic receptors with 3 micrograms/ml flaxedil before bee venom application sustained normal contraction of gastrocnemius muscle. 3. The electrical activity of duodenum rabbits was recorded before and after the application of 1 microgram/ml venom solution. The venom has depressed the amplitude of the muscle contraction after 15 min pretreatment with atropine nearly abolished the depressor effect of the venom on smooth muscle. 4. In concentrations from 0.5-2 micrograms/ml, bee venom caused decrease of heart rate of isolated perfused toad heart. This bradycardia was accompanied by elongation in the P-R interval. A gradual and progressive increase in the R-wave amplitude reflected a positive inotropism of the venom. Application of 5 micrograms/ml verapamil, a calcium channels blocking agent, abolished the noticed effect of the venom. 5. Marked electrocardiographic changes were produced within minutes of the venom application on the isolated perfused hearts, like marked injury current (elevation or depression of the S-T segment), atrioventricular conduction disturbances and sinus arrhythmias. Atropine and nicotine could decrease the toxic effect of the venom on the myocardium. 6. Results of the present work lead to the suggestion that bee venom is mediated through the peripheral cholinergic neurotransmitter system. General neurotoxicity of an inhibitory nature involving the autonomic as well as neuromuscular system are established as a result of the venom, meanwhile a direct effect on the myocardium membrane stabilization has been suggested.

Hemoglobin encapsulation in vesicles retards NO and CO binding and O2 release when perfused through narrow gas-permeable tubes.

PubMed

Sakai, Hiromi; Okuda, Naoto; Sato, Atsushi; Yamaue, Tatsuya; Takeoka, Shinji; Tsuchida, Eishun

2010-03-01

Intravenous administration of cell-free Hb induces vasoconstriction and circulatory disorders, presumably because of the intrinsic affinities to endogenous nitric oxide (NO) and carbon monoxide (CO) as vasorelaxation factors and because of the facilitated O(2) release that might induce autoregulatory vasoconstriction. We examined these gas reactions when Hb-containing solutions of four kinds were perfused through artificial narrow tubes at a practical Hb concentration (10 g/dl). Purified Hb solution, polymerized bovine Hb (Poly(B)Hb), encapsulated Hb [Hb-vesicles (HbV), 279 nm], and red blood cells (RBCs) were perfused through a gas-permeable narrow tube (25 microm inner diameter) at 1 mm/s centerline velocity. The level of reactions was determined microscopically based on the visible-light absorption spectrum of Hb. When the tube was immersed in NO and CO atmospheres, both NO binding and CO binding of deoxygenated Hb (deoxy-Hb) and Poly(B)Hb in the tube was faster than those of HbV and RBCs, and HbV and RBCs showed almost identical binding rates. When the tube was immersed in a N(2) atmosphere, oxygenated Hb and Poly(B)Hb showed much faster O(2) release than did HbV and RBCs. Poly(B)Hb showed a faster reaction than Hb because of the lower O(2) affinity of Poly(B)Hb than Hb. The diffusion process of the particles was simulated using Navier-Stokes and Maxwell-Stefan equations. Results clarified that small Hb (6 nm) diffuses laterally and mixes rapidly. However, the large-dimension HbV shows no such rapid diffusion. The purely physicochemical differences in diffusivity of the particles and the resulting reactivity with gas molecules are one factor inducing biological vasoconstriction of Hb-based oxygen carriers.

Measurement of the efficacy of 2% lipid in reversing bupivacaine- induced asystole in isolated rat hearts

PubMed Central

2014-01-01

Background The reversal efficacy of 2% lipid emulsion in cardiac asystole induced by different concentrations of bupivacaine is poorly defined and needs to be determined. Methods Forty-two male Sprague–Dawley rats were randomly divided into seven groups: B40, B60, B80, B100, B120, B140 and B160, n = 6. The Langendorff isolated heart perfusion model was used, which consisted of a balanced perfusion with Krebs-Henseleit solution for 25 minutes and a continuous infusion of 100 μmol/L bupivacaine until asystole had been induced for 3 minutes. The hearts in the seven groups were perfused with Krebs-Henseleit solution containing a 2% lipid emulsion, and 40, 60, 80, 100, 120, 140 or 160 μmol/L bupivacaine, respectively. Cardiac recovery was defined as a spontaneous and regular rhythm with a rate-pressure product > 10% of the baseline value for more than 1 minute. Our primary outcome was the rate-pressure product 25 minutes after cardiac recovery. Other cardiac function parameters were also recorded. Results All groups demonstrated cardiac recovery. During the recovery phase, heart rate, rate-pressure product, the maximum left ventricular pressure rise and decline in heart rate in the B120-B160 groups was significantly lower than those in the B40-B80 groups (P < 0.05). The concentration of bupivacaine and the reversal effects of a 2% lipid emulsion showed a typical transoid S-shaped curve, R2 = 0.9983, IC50 value was 102.5 μmol/L (95% CI: 92.44 - 113.6). Conclusions There is a concentration-response relationship between the concentrations of bupivacaine and the reversal effects of 2% lipid emulsion. PMID:25089118

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

NASA Astrophysics Data System (ADS)

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

2014-03-01

The acute ischemic stroke is a leading cause for death and disability in the industry nations. In case of a present acute ischemic stroke, the prediction of the future tissue outcome is of high interest for the clinicians as it can be used to support therapy decision making. Within this context, it has already been shown that the voxel-wise multi-parametric tissue outcome prediction leads to more promising results compared to single channel perfusion map thresholding. Most previously published multi-parametric predictions employ information from perfusion maps derived from perfusion-weighted MRI together with other image sequences such as diffusion-weighted MRI. However, it remains unclear if the typically calculated perfusion maps used for this purpose really include all valuable information from the PWI dataset for an optimal tissue outcome prediction. To investigate this problem in more detail, two different methods to predict tissue outcome using a k-nearest-neighbor approach were developed in this work and evaluated based on 18 datasets of acute stroke patients with known tissue outcome. The first method integrates apparent diffusion coefficient and perfusion parameter (Tmax, MTT, CBV, CBF) information for the voxel-wise prediction, while the second method employs also apparent diffusion coefficient information but the complete perfusion information in terms of the voxel-wise residue functions instead of the perfusion parameter maps for the voxel-wise prediction. Overall, the comparison of the results of the two prediction methods for the 18 patients using a leave-one-out cross validation revealed no considerable differences. Quantitatively, the parameter-based prediction of tissue outcome led to a mean Dice coefficient of 0.474, while the prediction using the residue functions led to a mean Dice coefficient of 0.461. Thus, it may be concluded from the results of this study that the perfusion parameter maps typically derived from PWI datasets include all valuable perfusion information required for a voxel-based tissue outcome prediction, while the complete analysis of the residue functions does not add further benefits for the voxel-wise tissue outcome prediction and is also computationally more expensive.

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.

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 assess blood supply of lung cancer patients. Preliminary results demonstrated that the iodine uptake relevant parameters derived from DE-CT significantly correlated with perfusion parameters derived from DI-PCT.

The dream of a one-stop-shop: Meta-analysis on myocardial perfusion CT.

PubMed

Pelgrim, Gert Jan; Dorrius, Monique; Xie, Xueqian; den Dekker, Martijn A M; Schoepf, U Joseph; Henzler, Thomas; Oudkerk, Matthijs; Vliegenthart, Rozemarijn

2015-12-01

To determine the diagnostic performance of computed tomography (CT) perfusion techniques for the detection of functionally relevant coronary artery disease (CAD) in comparison to reference standards, including invasive coronary angiography (ICA), single photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI). PubMed, Web of Knowledge and Embase were searched from January 1, 1998 until July 1, 2014. The search yielded 9475 articles. After duplicate removal, 6041 were screened on title and abstract. The resulting 276 articles were independently analyzed in full-text by two reviewers, and included if the inclusion criteria were met. The articles reporting diagnostic parameters including true positive, true negative, false positive and false negative were subsequently evaluated for the meta-analysis. Results were pooled according to CT perfusion technique, namely snapshot techniques: single-phase rest, single-phase stress, single-phase dual-energy stress and combined coronary CT angiography [rest] and single-phase stress, as well the dynamic technique: dynamic stress CT perfusion. Twenty-two articles were included in the meta-analysis (1507 subjects). Pooled per-patient sensitivity and specificity of single-phase rest CT compared to rest SPECT were 89% (95% confidence interval [CI], 82-94%) and 88% (95% CI, 78-94%), respectively. Vessel-based sensitivity and specificity of single-phase stress CT compared to ICA-based >70% stenosis were 82% (95% CI, 64-92%) and 78% (95% CI, 61-89%). Segment-based sensitivity and specificity of single-phase dual-energy stress CT in comparison to stress MRI were 75% (95% CI, 60-85%) and 95% (95% CI, 80-99%). Segment-based sensitivity and specificity of dynamic stress CT perfusion compared to stress SPECT were 77% (95% CI, 67-85) and 89% (95% CI, 78-95%). For combined coronary CT angiography and single-phase stress CT, vessel-based sensitivity and specificity in comparison to ICA-based >50% stenosis were 84% (95% CI, 67-93%) and 93% (95% CI, 89-96%). This meta-analysis shows considerable variation in techniques and reference standards for CT of myocardial blood supply. While CT seems sensitive and specific for evaluation of hemodynamically relevant CAD, studies so far are limited in size. Standardization of myocardial perfusion CT technique is essential. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Effect of increased pressure during pulsatile pump perfusion of deceased donor kidneys in transplantation.

PubMed

Patel, S K; Pankewycz, O G; Weber-Shrikant, E; Zachariah, M; Kohli, R; Nader, N D; Laftavi, M R

2012-09-01

Pulsatile pump perfusion of potential kidneys for transplantation is known to decrease the rate of delayed graft function (DGF) and improve their 1-year survival. Flow and resistance parameters are often used to determine the suitability of kidneys for transplantation. Kidneys with low flow rates are often subjected to higher pressures to improve flow. This study evaluated the effect of higher pump pressures on posttransplant renal function. We performed a retrospective analysis of 73 deceased donor kidneys preserved using pump perfusion (LifePort) at our center between May 2006 and September 2009. We calculated the mean pump pressure (MP) for the duration of perfusion of each kidney, using systolic pressure (SP) and diastolic pressure (DP) readings with the following formula: (MP = DP + 1/3 (SP - DP). The kidneys were divided into a low (LP; n = 49) and a high-pressure group (HP; n = 24) based on a MP cutoff value of 23 mm Hg. The two groups were then compared for differences in perfusion dynamics and primary endpoints including DGF and 1-year graft survival. Statistical analysis was performed using paired Student t test and chi-square analysis. The two groups were comparable for donor age, extended criteria, sensitization, and cold ischemic times. They differed significantly in higher initial (0.65 ± 0.4 versus 0.4 ± 0.2, P = .01), average (0.25 ± 0.08 versus 0.18 ± 0.06, P = .0006), and terminal resistance (0.21 ± 0.07 versus 0.17 ± 0.06, P = .008) of HP versus LP kidneys. Flow rates were comparable between the two groups. DGF was higher in HP kidneys (75% versus 40%, P = .006) with similar 1-year graft survival (87.5% versus 89%, P = .7). Perfusate flow through a kidney can be improved by increasing pressure settings to overcome elevated resistance. This maneuver was not associated with a lower rate of DGF after transplantation. One-year graft survival remained unaffected. Copyright © 2012 Elsevier Inc. All rights reserved.

Chalk in the prime.

PubMed Central

Yeo, H; Doyle, T; Saynor, R; Smith, G H

1986-01-01

After observations of cloudiness in the perfusion circuit at open intracardiac operations, laboratory experiments showed a precipitate in a Hartmann's solution (compound sodium lactate solution, Ringer-lactate) and sodium bicarbonate based priming fluid used for cardiopulmonary bypass. The precipitate was found to consist of calcium carbonate crystals. The crystals were not dissolved by adding plasma proteins, nor were they sufficiently cleared from the extracorporeal circuit by a 40 microns filter in the arterial line. The crystals may embolise in microvascular beds and thus be a cause of postoperative morbidity. The practice of adding sodium bicarbonate to the pump prime may be unnecessary. Images PMID:3010485

Fractal analysis of the ischemic transition region in chronic ischemic heart disease using magnetic resonance imaging.

PubMed

Michallek, Florian; Dewey, Marc

2017-04-01

To introduce a novel hypothesis and method to characterise pathomechanisms underlying myocardial ischemia in chronic ischemic heart disease by local fractal analysis (FA) of the ischemic myocardial transition region in perfusion imaging. Vascular mechanisms to compensate ischemia are regulated at various vascular scales with their superimposed perfusion pattern being hypothetically self-similar. Dedicated FA software ("FraktalWandler") has been developed. Fractal dimensions during first-pass (FD first-pass ) and recirculation (FD recirculation ) are hypothesised to indicate the predominating pathomechanism and ischemic severity, respectively. Twenty-six patients with evidence of myocardial ischemia in 108 ischemic myocardial segments on magnetic resonance imaging (MRI) were analysed. The 40th and 60th percentiles of FD first-pass were used for pathomechanical classification, assigning lesions with FD first-pass  ≤ 2.335 to predominating coronary microvascular dysfunction (CMD) and ≥2.387 to predominating coronary artery disease (CAD). Optimal classification point in ROC analysis was FD first-pass  = 2.358. FD recirculation correlated moderately with per cent diameter stenosis in invasive coronary angiography in lesions classified CAD (r = 0.472, p = 0.001) but not CMD (r = 0.082, p = 0.600). The ischemic transition region may provide information on pathomechanical composition and severity of myocardial ischemia. FA of this region is feasible and may improve diagnosis compared to traditional noninvasive myocardial perfusion analysis. • A novel hypothesis and method is introduced to pathophysiologically characterise myocardial ischemia. • The ischemic transition region appears a meaningful diagnostic target in perfusion imaging. • Fractal analysis may characterise pathomechanical composition and severity of myocardial ischemia.

Long-term myocardial preservation: beneficial and additive effects of polarized arrest (Na+-channel blockade), Na+/H+-exchange inhibition, and Na+/K+/2Cl- -cotransport inhibition combined with calcium desensitization.

PubMed

Snabaitis, A K; Chambers, D

1999-11-27

Polarized arrest, induced by tetrodotoxin (TTX) at an optimal concentration of 22 micromol/L, has been shown to reduce ionic imbalance and improve myocardial preservation compared with hyperkalemic (depolarized) arrest. Additional pharmacologic manipulation of ionic changes (involving inhibition of Na+ influx by the Na+/H+ exchanger [HOE694] and Na+/K+/2Cl- cotransporter [furosemide], and calcium desensitization [BDM]) may further improve long-term preservation. In this study, we (i) established optimal concentrations of each drug, (ii) determined additive effects of optimal concentrations of each drug and (iii) compared our optimal preservation solution to an established depolarizing cardioplegia (St Thomas' Hospital solution No 2: STH2) used during long-term hypothermic storage for clinical transplantation. The isolated working rat heart, perfused with Krebs Henseleit (KH) buffer was used; cardiac function was measured after 20 min aerobic working mode perfusion. The hearts (n=6/group) were arrested with a 2 ml infusion (for 30 sec) of the polarizing (control) solution (22 micromol/L TTX in KH) or control+drug and subjected to 5 hr or 8 hr of storage at 7.5 degrees C in the arresting solution. Postischemic function during reperfusion was measured (expressed as percentage of preischemic function). Dose-response studies established optimal concentrations of HOE694 (10 micromol/L), furosemide (1.0 micromol/L) and BDM (30 mmol/L) in the polarizing (control) solution. Sequential addition to the control solution (Group I) of optimal concentrations of HOE694 (Group II), furosemide (Group III), and BDM (Group IV) were compared with STH2 (Group V); postischemic recovery of aortic flow was 29+/-7%, 49+/-6%*, 56+/-2%*, 76+/-3%*, and 25+/-6%, respectively (*P<0.05 vs. I and V). Creatine kinase leakage was lowest, and myocardial ATP content was highest in Group IV. A polarizing preservation solution (KH+TTX) containing HOE694, furosemide, and BDM significantly enhanced long-term preservation compared with an optimized depolarizing solution (STH2) used clinically for long-term donor heart preservation.

Temporal and spectral properties of esophageal mucosal blood perfusion: a comparison between normal subjects and nutcracker esophagus patients.

PubMed

Zifan, A; Jiang, Y; Mittal, R K

2017-02-01

The mechanism of esophageal pain in patients with nutcracker esophagus (NE) and other esophageal motor disorders is not known. Our recent study shows that baseline esophageal mucosal perfusion, measured by laser Doppler perfusion monitoring, is lower in NE patients compared to controls. The goal of our current study was to perform a more detailed analysis of esophageal mucosal blood perfusion (EMBP) waveform of NE patients and controls to determine the optimal EMBP biomarkers that combined with suitable statistical learning models produce robust discrimination between the two groups. Laser Doppler recordings of 10 normal subjects (mean age 43 ± 15 years, 8 males) and 10 patients (mean age 47 ± 5.5 years., 8 males) with NE were analyzed. Time and frequency domain features were extracted from the first twenty-minute recordings of the EMBP waveforms, statistically ranked according to four independent evaluation criterions, and analyzed using two statistical learning models, namely, logistic regression (LR) and support vector machines (SVM). The top three ranked predictors between the two groups were the 0.5 and 0.75 perfusion quantile values followed by the surface of the EMBP power spectrum in the frequency domain. ROC curve ranking produced a cross-validated AUC (area under the curve) of 0.93 for SVM and 0.90 for LR. We show that as a group NE patients have lower perfusion values compared to controls, however, there is an overlap between the two groups, suggesting that not all NE patients suffer from low mucosal perfusion levels. © 2016 John Wiley & Sons Ltd.

Dynamic infrared thermography (DIRT) for assessment of skin blood perfusion in cranioplasty: a proof of concept for qualitative comparison with the standard indocyanine green video angiography (ICGA).

PubMed

Rathmann, P; Chalopin, C; Halama, D; Giri, P; Meixensberger, J; Lindner, D

2018-03-01

Complications in wound healing after neurosurgical operations occur often due to scarred dehiscence with skin blood perfusion disturbance. The standard imaging method for intraoperative skin perfusion assessment is the invasive indocyanine green video angiography (ICGA). The noninvasive dynamic infrared thermography (DIRT) is a promising alternative modality that was evaluated by comparison with ICGA. The study was carried out in two parts: (1) investigation of technical conditions for intraoperative use of DIRT for its comparison with ICGA, and (2) visual and quantitative comparison of both modalities in a proof of concept on nine patients. Time-temperature curves in DIRT and time-intensity curves in ICGA for defined regions of interest were analyzed. New perfusion parameters were defined in DIRT and compared with the usual perfusion parameters in ICGA. The visual observation of the image data in DIRT and ICGA showed that operation material, anatomical structures and skin perfusion are represented similarly in both modalities. Although the analysis of the curves and perfusion parameter values showed differences between patients, no complications were observed clinically. These differences were represented in DIRT and ICGA equivalently. DIRT has shown a great potential for intraoperative use, with several advantages over ICGA. The technique is passive, contactless and noninvasive. The practicability of the intraoperative recording of the same operation field section with ICGA and DIRT has been demonstrated. The promising results of this proof of concept provide a basis for a trial with a larger number of patients.

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.

Effect of D2O on growth properties and chemical structure of annual ryegrass (Lolium multiflorum)

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

Evans, Barbara R; Bali, Garima; Reeves, David T

2014-01-01

In present paper, we report the production and detailed structural analysis of deuterium-enriched rye grass (Lolium multiflorum) for neutron scattering experiments. An efficient method to produce deuterated biomass was developed by designing hydroponic perfusion chambers. In preliminary studies, the partial deuterated rye samples were grown in increasing levels of D2O to study the seed germination and the level of deuterium incorporation as a function of D2O concentration. Solution NMR method indicated 36.9 % deuterium incorporation in 50 % D2O grown annual rye samples and further significant increase in the deuterium incorporation level was observed by germinating the rye seedlings inmore » H2O and growing in 50 % D2O inside the perfusion chambers. Moreover, in an effort to compare the substrate characteristics related to enzymatic hydrolysis on deuterated and protiated version of biomass, annual rye grown in 50 % D2O was selected for detailed biomass characterization studies. The compositional analyses, degree of polymerization and cellulose crystallinity were compared with its protiated control. The cellulose molecular weight indicated slight variation with deuteration; however, hemicellulose molecular weights and cellulose crystallinity remain unaffected with the deuteration. Besides the minor differences in biomass components, the development of deuterated biomass for neutron scattering application is essential to understand the complex biomass conversion processes.« less

[Sodium chloride 0.9%: nephrotoxic crystalloid?].

PubMed

Dombre, Vincent; De Seigneux, Sophie; Schiffer, Eduardo

2016-02-03

Sodium chloride 0.9%, often incorrectly called physiological saline, contains higher concentration of chloride compared to plasma. It is known that the administration of sodium chloride 0.9% can cause hyperchloremic metabolic acidosis in a reproducible manner. The elevated chloride concentration in 0.9% NaCl solution can also adversely affect renal perfusion. This effect is thought to be induced by hyperchloremia that causes renal artery vasoconstriction. For these reasons, the use of 0.9% NaCl solution is raising attention and some would advocate the use of a more "physiological" solution, such as balanced solutions that contain a level of chloride closer to that of plasma. Few prospective, randomized, controlled trials are available today and most were done in a perioperative setting. Some studies suggest that the chloride excess in 0.9% NaCl solution could have clinical consequences; however, this remains to be established by quality randomized controlled trials.

Quantitative relationship between the octanol/water partition coefficient and the diffusion limitation of the exchange between adipose and blood

PubMed Central

2010-01-01

Background The goal of physiologically based pharmacokinetics (PBPK) is to predict drug kinetics from an understanding of the organ/blood exchange. The standard approach is to assume that the organ is "flow limited" which means that the venous blood leaving the organ equilibrates with the well-stirred tissue compartment. Although this assumption is valid for most solutes, it has been shown to be incorrect for several very highly fat soluble compounds which appear to be "diffusion limited". This paper describes the physical basis of this adipose diffusion limitation and its quantitative dependence on the blood/water (Kbld-wat) and octanol/water (Kow) partition coefficient. Methods Experimental measurements of the time dependent rat blood and adipose concentration following either intravenous or oral input were used to estimate the "apparent" adipose perfusion rate (FA) assuming that the tissue is flow limited. It is shown that the ratio of FA to the anatomic perfusion rate (F) provides a measure of the diffusion limitation. A quantitative relationship between this diffusion limitation and Kbld-wat and Kow is derived. This analysis was applied to previously published data, including the Oberg et. al. measurements of the rat plasma and adipose tissue concentration following an oral dose of a mixture of 13 different polychlorinated biphenyls. Results Solutes become diffusion limited at values of log Kow greater than about 5.6, with the adipose-blood exchange rate reduced by a factor of about 30 for a solute with a log Kow of 7.36. Quantitatively, a plot of FA/F versus Kow is well described assuming an adipose permeability-surface area product (PS) of 750/min. This PS corresponds to a 0.14 micron aqueous layer separating the well-stirred blood from the adipose lipid. This is approximately equal to the thickness of the rat adipose capillary endothelium. Conclusions These results can be used to quantitate the adipose-blood diffusion limitation as a function of Kow. This is especially important for the highly fat soluble persistent organic chemicals (e.g. polychlorinated biphenyls, dioxins) whose pharmacokinetics are primarily determined by the adipose-blood exchange kinetics. PMID:20055995

Quantitative relationship between the octanol/water partition coefficient and the diffusion limitation of the exchange between adipose and blood.

PubMed

Levitt, David G

2010-01-07

The goal of physiologically based pharmacokinetics (PBPK) is to predict drug kinetics from an understanding of the organ/blood exchange. The standard approach is to assume that the organ is "flow limited" which means that the venous blood leaving the organ equilibrates with the well-stirred tissue compartment. Although this assumption is valid for most solutes, it has been shown to be incorrect for several very highly fat soluble compounds which appear to be "diffusion limited". This paper describes the physical basis of this adipose diffusion limitation and its quantitative dependence on the blood/water (Kbld-wat) and octanol/water (Kow) partition coefficient. Experimental measurements of the time dependent rat blood and adipose concentration following either intravenous or oral input were used to estimate the "apparent" adipose perfusion rate (FA) assuming that the tissue is flow limited. It is shown that the ratio of FA to the anatomic perfusion rate (F) provides a measure of the diffusion limitation. A quantitative relationship between this diffusion limitation and Kbld-wat and Kow is derived. This analysis was applied to previously published data, including the Oberg et. al. measurements of the rat plasma and adipose tissue concentration following an oral dose of a mixture of 13 different polychlorinated biphenyls. Solutes become diffusion limited at values of log Kow greater than about 5.6, with the adipose-blood exchange rate reduced by a factor of about 30 for a solute with a log Kow of 7.36. Quantitatively, a plot of FA/F versus Kow is well described assuming an adipose permeability-surface area product (PS) of 750/min. This PS corresponds to a 0.14 micron aqueous layer separating the well-stirred blood from the adipose lipid. This is approximately equal to the thickness of the rat adipose capillary endothelium. These results can be used to quantitate the adipose-blood diffusion limitation as a function of Kow. This is especially important for the highly fat soluble persistent organic chemicals (e.g. polychlorinated biphenyls, dioxins) whose pharmacokinetics are primarily determined by the adipose-blood exchange kinetics.

Meshless Method with Operator Splitting Technique for Transient Nonlinear Bioheat Transfer in Two-Dimensional Skin Tissues

PubMed Central

Zhang, Ze-Wei; Wang, Hui; Qin, Qing-Hua

2015-01-01

A meshless numerical scheme combining the operator splitting method (OSM), the radial basis function (RBF) interpolation, and the method of fundamental solutions (MFS) is developed for solving transient nonlinear bioheat problems in two-dimensional (2D) skin tissues. In the numerical scheme, the nonlinearity caused by linear and exponential relationships of temperature-dependent blood perfusion rate (TDBPR) is taken into consideration. In the analysis, the OSM is used first to separate the Laplacian operator and the nonlinear source term, and then the second-order time-stepping schemes are employed for approximating two splitting operators to convert the original governing equation into a linear nonhomogeneous Helmholtz-type governing equation (NHGE) at each time step. Subsequently, the RBF interpolation and the MFS involving the fundamental solution of the Laplace equation are respectively employed to obtain approximated particular and homogeneous solutions of the nonhomogeneous Helmholtz-type governing equation. Finally, the full fields consisting of the particular and homogeneous solutions are enforced to fit the NHGE at interpolation points and the boundary conditions at boundary collocations for determining unknowns at each time step. The proposed method is verified by comparison of other methods. Furthermore, the sensitivity of the coefficients in the cases of a linear and an exponential relationship of TDBPR is investigated to reveal their bioheat effect on the skin tissue. PMID:25603180

Meshless method with operator splitting technique for transient nonlinear bioheat transfer in two-dimensional skin tissues.

PubMed

Zhang, Ze-Wei; Wang, Hui; Qin, Qing-Hua

2015-01-16

A meshless numerical scheme combining the operator splitting method (OSM), the radial basis function (RBF) interpolation, and the method of fundamental solutions (MFS) is developed for solving transient nonlinear bioheat problems in two-dimensional (2D) skin tissues. In the numerical scheme, the nonlinearity caused by linear and exponential relationships of temperature-dependent blood perfusion rate (TDBPR) is taken into consideration. In the analysis, the OSM is used first to separate the Laplacian operator and the nonlinear source term, and then the second-order time-stepping schemes are employed for approximating two splitting operators to convert the original governing equation into a linear nonhomogeneous Helmholtz-type governing equation (NHGE) at each time step. Subsequently, the RBF interpolation and the MFS involving the fundamental solution of the Laplace equation are respectively employed to obtain approximated particular and homogeneous solutions of the nonhomogeneous Helmholtz-type governing equation. Finally, the full fields consisting of the particular and homogeneous solutions are enforced to fit the NHGE at interpolation points and the boundary conditions at boundary collocations for determining unknowns at each time step. The proposed method is verified by comparison of other methods. Furthermore, the sensitivity of the coefficients in the cases of a linear and an exponential relationship of TDBPR is investigated to reveal their bioheat effect on the skin tissue.

Shortened Mean Transit Time in CT Perfusion With Singular Value Decomposition Analysis in Acute Cerebral Infarction: Quantitative Evaluation and Comparison With Various CT Perfusion Parameters.

PubMed

Murayama, Kazuhiro; Katada, Kazuhiro; Hayakawa, Motoharu; Toyama, Hiroshi

We aimed to clarify the cause of shortened mean transit time (MTT) in acute ischemic cerebrovascular disease and examined its relationship with reperfusion. Twenty-three patients with acute ischemic cerebrovascular disease underwent whole-brain computed tomography perfusion (CTP). The maximum MTT (MTTmax), minimum MTT (MTTmin), ratio of maximum and minimum MTT (MTTmin/max), and minimum cerebral blood volume (CBV) (CBVmin) were measured by automatic region of interest analysis. Diffusion weighted image was performed to calculate infarction volume. We compared these CTP parameters between reperfusion and nonreperfusion groups and calculated correlation coefficients between the infarction core volume and CTP parameters. Significant differences were observed between reperfusion and nonreperfusion groups (MTTmin/max: P = 0.014; CBVmin ratio: P = 0.038). Regression analysis of CTP and high-intensity volume on diffusion weighted image showed negative correlation (CBVmin ratio: r = -0.41; MTTmin/max: r = -0.30; MTTmin ratio: r = -0.27). A region of shortened MTT indicated obstructed blood flow, which was attributed to the singular value decomposition method error.

Hippocampal perfusion predicts impending neurodegeneration in REM sleep behavior disorder.

PubMed

Dang-Vu, Thien Thanh; Gagnon, Jean-François; Vendette, Mélanie; Soucy, Jean-Paul; Postuma, Ronald B; Montplaisir, Jacques

2012-12-11

Patients with idiopathic REM sleep behavior disorder (IRBD) are at risk for developing Parkinson disease (PD) and dementia with Lewy bodies (DLB). We aimed to identify functional brain imaging patterns predicting the emergence of PD and DLB in patients with IRBD, using SPECT with (99m)Tc-ethylene cysteinate dimer (ECD). Twenty patients with IRBD were scanned at baseline during wakefulness using (99m)Tc-ECD SPECT. After a follow-up of 3 years on average, patients were divided into 2 groups according to whether or not they developed defined neurodegenerative disease (PD, DLB). SPECT data analysis comparing regional cerebral blood flow (rCBF) between groups assessed whether specific brain perfusion patterns were associated with subsequent clinical evolution. Regression analysis between rCBF and clinical markers of neurodegeneration (motor, color vision, olfaction) looked for neural structures involved in this process. Of the 20 patients with IRBD recruited for this study, 10 converted to PD or DLB during the follow-up. rCBF at baseline was increased in the hippocampus of patients who would later convert compared with those who would not (p < 0.05 corrected). Hippocampal perfusion was correlated with motor and color vision scores across all IRBD patients. (99m)Tc-ECD SPECT identifies patients with IRBD at risk for conversion to other neurodegenerative disorders such as PD or DLB; disease progression in IRBD is predicted by abnormal perfusion in the hippocampus at baseline. Perfusion within this structure is correlated with clinical markers of neurodegeneration, further suggesting its involvement in the development of presumed synucleinopathies.

Effectiveness of diagnostic strategies in suspected delayed cerebral ischemia: a decision analysis.

PubMed

Rawal, Sapna; Barnett, Carolina; John-Baptiste, Ava; Thein, Hla-Hla; Krings, Timo; Rinkel, Gabriel J E

2015-01-01

Delayed cerebral ischemia (DCI) is a serious complication after aneurysmal subarachnoid hemorrhage. If DCI is suspected clinically, imaging methods designed to detect angiographic vasospasm or regional hypoperfusion are often used before instituting therapy. Uncertainty in the strength of the relationship between imaged vasospasm or perfusion deficits and DCI-related outcomes raises the question of whether imaging to select patients for therapy improves outcomes in clinical DCI. Decision analysis was performed using Markov models. Strategies were either to treat all patients immediately or to first undergo diagnostic testing by digital subtraction angiography or computed tomography angiography to assess for angiographic vasospasm, or computed tomography perfusion to assess for perfusion deficits. According to current practice guidelines, treatment consisted of induced hypertension. Outcomes were survival in terms of life-years and quality-adjusted life-years. When treatment was assumed to be ineffective in nonvasospasm patients, Treat All and digital subtraction angiography were equivalent strategies; when a moderate treatment effect was assumed in nonvasospasm patients, Treat All became the superior strategy. Treating all patients was also superior to selecting patients for treatment via computed tomography perfusion. One-way sensitivity analyses demonstrated that the models were robust; 2- and 3-way sensitivity analyses with variation of disease and treatment parameters reinforced dominance of the Treat All strategy. Imaging studies to test for the presence of angiographic vasospasm or perfusion deficits in patients with clinical DCI do not seem helpful in selecting which patients should undergo treatment and may not improve outcomes. Future directions include validating these results in prospective cohort studies. © 2014 American Heart Association, Inc.

Bacopa monnieri extract increases rat coronary flow and protects against myocardial ischemia/reperfusion injury.

PubMed

Srimachai, Sirintorn; Devaux, Sylvie; Demougeot, Celine; Kumphune, Sarawut; Ullrich, Nina D; Niggli, Ernst; Ingkaninan, Kornkanok; Kamkaew, Natakorn; Scholfield, C Norman; Tapechum, Sompol; Chootip, Krongkarn

2017-02-20

This study explored Bacopa monnieri, a medicinal Ayurvedic herb, as a cardioprotectant against ischemia/reperfusion injury using cardiac function and coronary flow as end-points. In normal isolated rat hearts, coronary flow, left ventricular developed pressure, heart rate, and functional recovery were measured using the Langendorff preparation. Hearts were perfused with either (i) Krebs-Henseleit (normal) solution, (control), or with 30, 100 μg/ml B. monnieri ethanolic extract (30 min), or (ii) with normal solution or extract for 10 min preceding no-perfusion ischemia (30 min) followed by reperfusion (30 min) with normal solution. Infarct volumes were measured by triphenyltetrazolium staining. L-type Ca 2+ -currents (I Ca, L ) were measured by whole-cell patching in HL-1 cells, a mouse atrial cardiomyocyte cell line. Cytotoxicity of B. monnieri was assessed in rat isolated ventricular myocytes by trypan blue exclusion. In normally perfused hearts, B. monnieri increased coronary flow by 63 ± 13% (30 μg/ml) and 216 ± 21% (100 μg/ml), compared to control (5 ± 3%) (n = 8-10, p < 0.001). B. monnieri treatment preceding ischemia/reperfusion improved left ventricular developed pressure by 84 ± 10% (30 μg/ml), 82 ± 10% (100 μg/ml) and 52 ± 6% (control) compared to pre- ischemia/reperfusion. Similarly, functional recovery showed a sustained increase. Moreover, B. monnieri (100 μg/ml) reduced the percentage of infarct size from 51 ± 2% (control) to 25 ± 2% (n = 6-8, p < 0.0001). B. monnieri (100 μg/ml) reduced I Ca, L by 63 ± 4% in HL-1 cells. Ventricular myocyte survival decreased at higher concentrations (50-1000 μg/ml) B. monnieri. B. monnieri improves myocardial function following ischemia/reperfusion injury through recovery of coronary blood flow, contractile force and decrease in infarct size. Thus this may lead to a novel cardioprotectant strategy.

Clinically Practical Magnetic Resonance Protocol for Improved Specifically in Breast Cancer Diagnosis

DTIC Science & Technology

2006-06-01

MRI, MRS, DCE, Choline , Perfusion, Breast Cancer, Diagnosis, Specificity 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18...data analysis, patient recruitment and consent, and can now perform these tasks independently. 3. Through interactions with the DOD representative (Dr...out at 4 cc/sec during perfusion MRI acquisition. The detection of an apparent choline compounds (Cho) peak (S/N > 2) at 3.23 ppm was defined as

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

PubMed

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

2018-03-01

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

Evaluation of General Toxicity, Anti-Oxidant Activity and Effects of Ficus Carica Leaves Extract on Ischemia/Reperfusion Injuries in Isolated Heart of Rat

PubMed Central

Allahyari, Saeideh; Delazar, Abbas; Najafi, Moslem

2014-01-01

Purpose: This study was aimed to evaluate general toxicity, anti-oxidant activity and effects of Ficus carica leaves extract on ischemia/reperfusion injuries. Methods: Antioxidant activity, total phenolic and flavonoid compounds of 70% methanolic extract of Ficus carica leaves were measured. The general toxicity test was carried out by brine shrimp lethality assay. Isolated hearts of male rats were mounted on a Langendorff apparatus and perfused with modified Krebs-Henseleit solution. In control group, the hearts were perfused with normal Krebs solution, however, treatment groups received enriched solution with the extract (0.04, 0.2 and 1 mg/ml) during stabilization and reperfusion (after 30 min global ischemia), respectively. Cardiac arrhythmias were analyzed and TTC method was used for infarct size determination. Results: The extract displayed antioxidant activity in the DPPH assay (RC50=0.06666 mg/ml). Total phenolic content was 12.29 mg GAE/100 g dry sample and the amount of flavonoids was calculated 40.729 mg/g. LD50 value by brine shrimp test was 0.158 mg/ml. The extract decreased number of VEBs, incidence and duration of Rev VF with clear reduction in infarct size and infarct volume (P<0.001). Conclusion: Ficus carica decreased ischemia/reperfusion-induced injuries. These protections are probably due to antioxidant capacity and the existence of flavonoid and phenolic compounds in the extract. PMID:25671192

Noise spatial nonuniformity and the impact of statistical image reconstruction in CT myocardial perfusion imaging.

PubMed

Lauzier, Pascal Theriault; Tang, Jie; Speidel, Michael A; Chen, Guang-Hong

2012-07-01

To achieve high temporal resolution in CT myocardial perfusion imaging (MPI), images are often reconstructed using filtered backprojection (FBP) algorithms from data acquired within a short-scan angular range. However, the variation in the central angle from one time frame to the next in gated short scans has been shown to create detrimental partial scan artifacts when performing quantitative MPI measurements. This study has two main purposes. (1) To demonstrate the existence of a distinct detrimental effect in short-scan FBP, i.e., the introduction of a nonuniform spatial image noise distribution; this nonuniformity can lead to unexpectedly high image noise and streaking artifacts, which may affect CT MPI quantification. (2) To demonstrate that statistical image reconstruction (SIR) algorithms can be a potential solution to address the nonuniform spatial noise distribution problem and can also lead to radiation dose reduction in the context of CT MPI. Projection datasets from a numerically simulated perfusion phantom and an in vivo animal myocardial perfusion CT scan were used in this study. In the numerical phantom, multiple realizations of Poisson noise were added to projection data at each time frame to investigate the spatial distribution of noise. Images from all datasets were reconstructed using both FBP and SIR reconstruction algorithms. To quantify the spatial distribution of noise, the mean and standard deviation were measured in several regions of interest (ROIs) and analyzed across time frames. In the in vivo study, two low-dose scans at tube currents of 25 and 50 mA were reconstructed using FBP and SIR. Quantitative perfusion metrics, namely, the normalized upslope (NUS), myocardial blood volume (MBV), and first moment transit time (FMT), were measured for two ROIs and compared to reference values obtained from a high-dose scan performed at 500 mA. Images reconstructed using FBP showed a highly nonuniform spatial distribution of noise. This spatial nonuniformity led to large fluctuations in the temporal direction. In the numerical phantom study, the level of noise was shown to vary by as much as 87% within a given image, and as much as 110% between different time frames for a ROI far from isocenter. The spatially nonuniform noise pattern was shown to correlate with the source trajectory and the object structure. In contrast, images reconstructed using SIR showed a highly uniform spatial distribution of noise, leading to smaller unexpected noise fluctuations in the temporal direction when a short scan angular range was used. In the numerical phantom study, the noise varied by less than 37% within a given image, and by less than 20% between different time frames. Also, the noise standard deviation in SIR images was on average half of that of FBP images. In the in vivo studies, the deviation observed between quantitative perfusion metrics measured from low-dose scans and high-dose scans was mitigated when SIR was used instead of FBP to reconstruct images. (1) Images reconstructed using FBP suffered from nonuniform spatial noise levels. This nonuniformity is another manifestation of the detrimental effects caused by short-scan reconstruction in CT MPI. (2) Images reconstructed using SIR had a much lower and more uniform noise level and thus can be used as a potential solution to address the FBP nonuniformity. (3) Given the improvement in the accuracy of the perfusion metrics when using SIR, it may be desirable to use a statistical reconstruction framework to perform low-dose dynamic CT MPI.

Noise spatial nonuniformity and the impact of statistical image reconstruction in CT myocardial perfusion imaging

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

Lauzier, Pascal Theriault; Tang Jie; Speidel, Michael A.

Purpose: To achieve high temporal resolution in CT myocardial perfusion imaging (MPI), images are often reconstructed using filtered backprojection (FBP) algorithms from data acquired within a short-scan angular range. However, the variation in the central angle from one time frame to the next in gated short scans has been shown to create detrimental partial scan artifacts when performing quantitative MPI measurements. This study has two main purposes. (1) To demonstrate the existence of a distinct detrimental effect in short-scan FBP, i.e., the introduction of a nonuniform spatial image noise distribution; this nonuniformity can lead to unexpectedly high image noise andmore » streaking artifacts, which may affect CT MPI quantification. (2) To demonstrate that statistical image reconstruction (SIR) algorithms can be a potential solution to address the nonuniform spatial noise distribution problem and can also lead to radiation dose reduction in the context of CT MPI. Methods: Projection datasets from a numerically simulated perfusion phantom and an in vivo animal myocardial perfusion CT scan were used in this study. In the numerical phantom, multiple realizations of Poisson noise were added to projection data at each time frame to investigate the spatial distribution of noise. Images from all datasets were reconstructed using both FBP and SIR reconstruction algorithms. To quantify the spatial distribution of noise, the mean and standard deviation were measured in several regions of interest (ROIs) and analyzed across time frames. In the in vivo study, two low-dose scans at tube currents of 25 and 50 mA were reconstructed using FBP and SIR. Quantitative perfusion metrics, namely, the normalized upslope (NUS), myocardial blood volume (MBV), and first moment transit time (FMT), were measured for two ROIs and compared to reference values obtained from a high-dose scan performed at 500 mA. Results: Images reconstructed using FBP showed a highly nonuniform spatial distribution of noise. This spatial nonuniformity led to large fluctuations in the temporal direction. In the numerical phantom study, the level of noise was shown to vary by as much as 87% within a given image, and as much as 110% between different time frames for a ROI far from isocenter. The spatially nonuniform noise pattern was shown to correlate with the source trajectory and the object structure. In contrast, images reconstructed using SIR showed a highly uniform spatial distribution of noise, leading to smaller unexpected noise fluctuations in the temporal direction when a short scan angular range was used. In the numerical phantom study, the noise varied by less than 37% within a given image, and by less than 20% between different time frames. Also, the noise standard deviation in SIR images was on average half of that of FBP images. In the in vivo studies, the deviation observed between quantitative perfusion metrics measured from low-dose scans and high-dose scans was mitigated when SIR was used instead of FBP to reconstruct images. Conclusions: (1) Images reconstructed using FBP suffered from nonuniform spatial noise levels. This nonuniformity is another manifestation of the detrimental effects caused by short-scan reconstruction in CT MPI. (2) Images reconstructed using SIR had a much lower and more uniform noise level and thus can be used as a potential solution to address the FBP nonuniformity. (3) Given the improvement in the accuracy of the perfusion metrics when using SIR, it may be desirable to use a statistical reconstruction framework to perform low-dose dynamic CT MPI.« less

Noise spatial nonuniformity and the impact of statistical image reconstruction in CT myocardial perfusion imaging

PubMed Central

Lauzier, Pascal Thériault; Tang, Jie; Speidel, Michael A.; Chen, Guang-Hong

2012-01-01

Purpose: To achieve high temporal resolution in CT myocardial perfusion imaging (MPI), images are often reconstructed using filtered backprojection (FBP) algorithms from data acquired within a short-scan angular range. However, the variation in the central angle from one time frame to the next in gated short scans has been shown to create detrimental partial scan artifacts when performing quantitative MPI measurements. This study has two main purposes. (1) To demonstrate the existence of a distinct detrimental effect in short-scan FBP, i.e., the introduction of a nonuniform spatial image noise distribution; this nonuniformity can lead to unexpectedly high image noise and streaking artifacts, which may affect CT MPI quantification. (2) To demonstrate that statistical image reconstruction (SIR) algorithms can be a potential solution to address the nonuniform spatial noise distribution problem and can also lead to radiation dose reduction in the context of CT MPI. Methods: Projection datasets from a numerically simulated perfusion phantom and an in vivo animal myocardial perfusion CT scan were used in this study. In the numerical phantom, multiple realizations of Poisson noise were added to projection data at each time frame to investigate the spatial distribution of noise. Images from all datasets were reconstructed using both FBP and SIR reconstruction algorithms. To quantify the spatial distribution of noise, the mean and standard deviation were measured in several regions of interest (ROIs) and analyzed across time frames. In the in vivo study, two low-dose scans at tube currents of 25 and 50 mA were reconstructed using FBP and SIR. Quantitative perfusion metrics, namely, the normalized upslope (NUS), myocardial blood volume (MBV), and first moment transit time (FMT), were measured for two ROIs and compared to reference values obtained from a high-dose scan performed at 500 mA. Results: Images reconstructed using FBP showed a highly nonuniform spatial distribution of noise. This spatial nonuniformity led to large fluctuations in the temporal direction. In the numerical phantom study, the level of noise was shown to vary by as much as 87% within a given image, and as much as 110% between different time frames for a ROI far from isocenter. The spatially nonuniform noise pattern was shown to correlate with the source trajectory and the object structure. In contrast, images reconstructed using SIR showed a highly uniform spatial distribution of noise, leading to smaller unexpected noise fluctuations in the temporal direction when a short scan angular range was used. In the numerical phantom study, the noise varied by less than 37% within a given image, and by less than 20% between different time frames. Also, the noise standard deviation in SIR images was on average half of that of FBP images. In the in vivo studies, the deviation observed between quantitative perfusion metrics measured from low-dose scans and high-dose scans was mitigated when SIR was used instead of FBP to reconstruct images. Conclusions: (1) Images reconstructed using FBP suffered from nonuniform spatial noise levels. This nonuniformity is another manifestation of the detrimental effects caused by short-scan reconstruction in CT MPI. (2) Images reconstructed using SIR had a much lower and more uniform noise level and thus can be used as a potential solution to address the FBP nonuniformity. (3) Given the improvement in the accuracy of the perfusion metrics when using SIR, it may be desirable to use a statistical reconstruction framework to perform low-dose dynamic CT MPI. PMID:22830741

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

PubMed Central

2014-01-01

Introduction We evaluate an innovative device consisting of an enteral feeding tube equipped with a photoplethysmography (PPG) sensor in contact with the duodenal mucosa. This study aims to determine if the PPG signal, composed of a continuous (PDC) and a pulsatile part (PAC), is a reliable method to assess gut perfusion in a porcine model of septic shock. Method Fourteen piglets were anesthetized and mechanically ventilated. They were randomly assigned to two groups: the nonseptic (NS) group received an infusion of Ringer’s lactate solution (RL) alone, the septic (S) group received in addition a suspension of live Pseudomonas aeruginosa. Heart rate (HR), pulse oximetry (SpO2), mean arterial pressure (MAP), cardiac index (CI) and serum lactates were recorded and gut microcirculation (GM) was monitored with a laser Doppler probe applied on the duodenal serosa. PDC and PAC were given by the PPG probe inserted in the duodenum. Data was collected every 15 minutes (t0, t15…) during 150 minutes (t150). After administration of the bacteria suspension (t0), resuscitation maneuvers were performed following a defined algorithm. GM PAC, and PDC were expressed as variation from baseline (GMvar, PACvar, PDCvar). Analysis of variance (ANOVA) with repeated measures was performed to compare hemodynamic variables, with Bonferroni correction as post hoc analysis on t0, t60 and t150. Results One piglet was withdrawn from analysis due to a defective probe. S group (six piglets) received resuscitation therapy while NS group (seven piglets) did not. A significant group effect was found for the all parameters except HR. Post hoc analysis found a significant decrease for GM and PAC at t60. The correlation between PAC, PDC and microcirculatory parameters were as follows: rPACvar-GMvar = 0.496, P <0.001, rPDCvar-GMvar = 0.244; P = 0.002. In the septic group, correlations were as follows: rPAC-lactate = -0.772, P <0.001; rPDC-lactate = -0.681, P <0.01). At the onset of shock, a decrease of PAC, PDC and GM occurred before the alteration of MAP. Conclusions PAC and PDC decreased at the onset of shock and were correlated with GM and lactate. These results confirm that PPG signal reliably reflects the early perfusion alteration of the gut. Further studies should assess the clinical use of this device. PMID:25030376

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

Engstroem, K; Casares-Magaz, O; Muren, L

Purpose: Multi-parametric MRI (mp-MRI) is being introduced in radiotherapy (RT) of prostate cancer, including for tumour delineation in focal boosting strategies. We recently developed an image-based tumour control probability model, based on cell density distributions derived from apparent diffusion coefficient (ADC) maps. Beyond tumour volume and cell densities, tumour hypoxia is also an important determinant of RT response. Since tissue perfusion from mp-MRI has been related to hypoxia we have explored the patterns of ADC and perfusion maps, and the relations between them, inside and outside prostate index lesions. Methods: ADC and perfusion maps from 20 prostate cancer patients weremore » used, with the prostate and index lesion delineated by a dedicated uro-radiologist. To reduce noise, the maps were averaged over a 3×3×3 voxel cube. Associations between different ADC and perfusion histogram parameters within the prostate, inside and outside the index lesion, were evaluated with the Pearson’s correlation coefficient. In the voxel-wise analysis, scatter plots of ADC vs perfusion were analysed for voxels in the prostate, inside and outside of the index lesion, again with the associations quantified with the Pearson’s correlation coefficient. Results: Overall ADC was lower inside the index lesion than in the normal prostate as opposed to ktrans that was higher inside the index lesion than outside. In the histogram analysis, the minimum ktrans was significantly correlated with the maximum ADC (Pearson=0.47; p=0.03). At the voxel level, 15 of the 20 cases had a statistically significant inverse correlation between ADC and perfusion inside the index lesion; ten of the cases had a Pearson < −0.4. Conclusion: The minimum value of ktrans across the tumour was correlated to the maximum ADC. However, on the voxel level, the ‘local’ ktrans in the index lesion is inversely (i.e. negatively) correlated to the ‘local’ ADC in most patients. Research agreement with Varian Medical Systems, not related to the work presented in this abstract.« less

Interpretative Guidelines and Possible Indications for Indocyanine Green Fluorescence Imaging in Robot-Assisted Sphincter-Saving Operations.

PubMed

Kim, Jin Cheon; Lee, Jong Lyul; Park, Seong Ho

2017-04-01

Since the introduction of indocyanine green angiography more than 25 years ago, few studies have presented interpretative guidelines for indocyanine green fluorescent imaging. We aimed to provide interpretative guidelines for indocyanine green fluorescent imaging through quantitative analysis and to suggest possible indications for indocyanine green fluorescent imaging during robot-assisted sphincter-saving operations. This is a retrospective observational study. This study was conducted at a single center. A cohort of 657 patients with rectal cancer who consecutively underwent curative robot-assisted sphincter-saving operations was enrolled between 2010 and 2016, including 310 patients with indocyanine green imaging (indocyanine green fluorescent imaging+ group) and 347 patients without indocyanine green imaging (indocyanine green fluorescent imaging- group). We tried to quantitatively define the indocyanine green fluorescent imaging findings based on perfusion (mesocolic and colic) time and perfusion intensity (5 grades) to provide probable indications. The anastomotic leakage rate was significantly lower in the indocyanine green fluorescent imaging+ group than in the indocyanine green fluorescent imaging- group (0.6% vs 5.2%) (OR, 0.123; 95% CI, 0.028-0.544; p = 0.006). Anastomotic stricture was closely correlated with anastomotic leakage (p = 0.002) and a short descending mesocolon (p = 0.003). Delayed perfusion (>60 s) and low perfusion intensity (1-2) were more frequently detected in patients with anastomotic stricture and marginal artery defects than in those without these factors (p ≤ 0.001). In addition, perfusion times greater than the mean were more frequently observed in patients aged >58 years, whereas low perfusion intensity was seen more in patients with short descending mesocolon and high ASA classes (≥3). The 300 patients in the indocyanine green fluorescent imaging- group underwent operations 3 years before indocyanine green fluorescent imaging. Quantitative analysis of indocyanine green fluorescent imaging may help prevent anastomotic complications during robot-assisted sphincter-saving operations, and may be of particular value in high-class ASA patients, older patients, and patients with a short descending mesocolon.

Prognostic value of high-dose dobutamine stress magnetic resonance imaging in 1,493 consecutive patients: assessment of myocardial wall motion and perfusion.

PubMed

Korosoglou, Grigorios; Elhmidi, Yacine; Steen, Henning; Schellberg, Dieter; Riedle, Nina; Ahrens, Johannes; Lehrke, Stephanie; Merten, Constanze; Lossnitzer, Dirk; Radeleff, Jannis; Zugck, Christian; Giannitsis, Evangelos; Katus, Hugo A

2010-10-05

This study sought to determine the prognostic value of wall motion and perfusion assessment during high-dose dobutamine stress (DS) cardiac magnetic resonance imaging (MRI) in a large patient cohort. DS-MRI offers the possibility to integrate myocardial perfusion and wall motion analysis in a single examination for the detection of coronary artery disease (CAD). A total of 1,493 consecutive patients with suspected or known CAD underwent DS-MRI, using a standard protocol in a 1.5-T magnetic resonance scanner. Wall motion and perfusion were assessed at baseline and during stress, and outcome data including cardiac death, nonfatal myocardial infarction ("hard events"), and "late" revascularization performed >90 days after the MR scans were collected during a 2 ± 1 year follow-up period. Fifty-three hard events, including 14 cardiac deaths and 39 nonfatal infarctions, occurred during the follow-up period, whereas 85 patients underwent "late" revascularization. Using multivariable regression analysis, an abnormal result for wall motion or perfusion during stress yielded the strongest independent prognostic value for both hard events and late revascularization, clearly surpassing that of clinical and baseline magnetic resonance parameters (for wall motion: adjusted hazard ratio [HR] of 5.9 [95% confidence interval (CI): 2.5 to 13.6] for hard events and of 3.1 [95% CI: 1.7 to 5.6] for late revascularization, and for perfusion: adjusted HR of 5.4 [95% CI: 2.3 to 12.9] for hard events and of 6.2 [95% CI: 3.3 to 11.3] for late revascularization, p < 0.001 for all). DS-MRI can accurately identify patients who are at increased risk for cardiac death and myocardial infarction, separating them from those with normal findings, who have very low risk for future cardiac events. (Prognostic Value of High Dose Dobutamine Stress Magnetic Resonance Imaging; NCT00837005). Copyright © 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

CCKB/gastrin receptors mediate changes in sodium and potassium absorption in the isolated perfused rat kidney.

PubMed

von Schrenck, T; Ahrens, M; de Weerth, A; Bobrowski, C; Wolf, G; Jonas, L; Jocks, T; Schulz, M; Bläker, M; Neumaier, M; Stahl, R A

2000-09-01

To evaluate the function of cholecystokinin B (CCKB)/gastrin receptors in the rat kidney, we identified the receptors by Northern blot and localized the receptors by immunohistochemistry. The functional effects of gastrin were studied under standardized in vitro conditions using the isolated perfused kidney. Rat kidneys were mounted in an organ bath by attaching the renal artery to a perfusion system. A catheter was inserted into the renal vein and the ureter to collect samples that were analyzed for the concentrations of electrolytes. After a preperfusion period, gastrin-17-I was given via the renal artery (10-8 to 10-6 mol/L). Subsequently, hemodynamic parameters (for example, perfusate flow) and changes in sodium and potassium absorption were determined. All data were subjected to a nonparametric analysis of variance and, in case of significant results, to subsequent paired comparisons by the a posteriori Wilcoxon test. Northern blot analysis detected CCKB receptor transcripts in total RNA isolated from kidneys. Immunohistochemistry localized CCKB receptors on tubules and collecting duct cells. Compared with controls, gastrin (10-6 mol/L) caused a decrease in the fractional sodium reabsorption (basal 80%, 10 minutes after application of gastrin 71%, after 20 minutes 62%, P < 0.05). This effect was inhibited by the CCKB receptor antagonist L-365,260. Gastrin decreased urinary potassium excretion at 10-8 and 10-6 mol/L [maximal decrease at 10-6 mol/L from baseline values (100%) to 49% after 10 minutes and to 69% after 20 minutes, P < 0.05, N = 6]. This effect was also abolished by the CCKB receptor antagonist L-365,260. Gastrin (10-6 mol/L) reduced perfusate flow by 31% (P < 0.05). CCKB receptors are expressed in the rat kidney on tubules and collecting ducts. These receptors mediate changes in renal potassium and sodium absorption. In addition, gastrin causes a decrease in perfusate flow, indicating that CCKB receptors might also modulate vascular resistance in the kidney.

Preretinal partial pressure of oxygen gradients before and after experimental pars plana vitrectomy.

PubMed

Petropoulos, Ioannis K; Pournaras, Jean-Antoine C; Stangos, Alexandros N; Pournaras, Constantin J

2013-01-01

To evaluate preretinal partial pressure of oxygen (PO2) gradients before and after experimental pars plana vitrectomy. Arteriolar, venous, and intervascular preretinal PO2 gradients were recorded in 7 minipigs during slow withdrawal of oxygen-sensitive microelectrodes (10-μm tip diameter) from the vitreoretinal interface to 2 mm into the vitreous cavity. Recordings were repeated after pars plana vitrectomy and balanced salt solution (BSS) intraocular perfusion. Arteriolar, venous, and intervascular preretinal PO2 at the vitreoretinal interface were 62.3 ± 13.8, 22.5 ± 3.3, and 17.0 ± 7.5 mmHg, respectively, before vitrectomy; 97.7 ± 19.9, 40.0 ± 21.9, and 56.3 ± 28.4 mmHg, respectively, immediately after vitrectomy; and 59.0 ± 27.4, 25.2 ± 3.0, and 21.5 ± 4.5 mmHg, respectively, 2½ hours after interruption of BSS perfusion. PO2 2 mm from the vitreoretinal interface was 28.4 ± 3.6 mmHg before vitrectomy; 151.8 ± 4.5 mmHg immediately after vitrectomy; and 34.8 ± 4.1 mmHg 2½ hours after interruption of BSS perfusion. PO2 gradients were still present after vitrectomy, with the same patterns as before vitrectomy. Preretinal PO2 gradients are not eliminated after pars plana vitrectomy. During BSS perfusion, vitreous cavity PO2 is very high. Interruption of BSS perfusion evokes progressive equilibration of vitreous cavity PO2 with concomitant progressive return of preretinal PO2 gradients to their previtrectomy patterns. This indicates that preretinal diffusion of oxygen is not altered after vitrectomy. The beneficial effect of vitrectomy in ischemic retinal diseases or macular edema may be related to other mechanisms, such as increased oxygen convection currents or removal of growth factors and cytokines secreted in the vitreous.

A randomized, controlled, double-blind crossover study on the effects of 1-L infusions of 6% hydroxyethyl starch suspended in 0.9% saline (voluven) and a balanced solution (Plasma Volume Redibag) on blood volume, renal blood flow velocity, and renal cortical tissue perfusion in healthy volunteers.

PubMed

Chowdhury, Abeed H; Cox, Eleanor F; Francis, Susan T; Lobo, Dileep N

2014-05-01

We compared the effects of intravenous administration of 6% hydroxyethyl starch (maize-derived) in 0.9% saline (Voluven; Fresenius Kabi, Runcorn, United Kingdom) and a "balanced" preparation of 6% hydroxyethyl starch (potato-derived) [Plasma Volume Redibag (PVR); Baxter Healthcare, Thetford, United Kingdom] on renal blood flow velocity and renal cortical tissue perfusion in humans using magnetic resonance imaging. Hyperchloremia resulting from 0.9% saline infusion may adversely affect renal hemodynamics when compared with balanced crystalloids. This phenomenon has not been studied with colloids. Twelve healthy adult male subjects received 1-L intravenous infusions of Voluven or PVR over 30 minutes in a randomized, double-blind manner, with crossover studies 7 to 10 days later. Magnetic resonance imaging proceeded for 60 minutes after commencement of infusion to measure renal artery blood flow velocity and renal cortical perfusion. Blood was sampled, and weight was recorded at 0, 30, 60, 120, 180, and 240 minutes. Mean peak serum chloride concentrations were 108 and 106 mmol/L, respectively, after Voluven and PVR infusion (P = 0.032). Changes in blood volume (P = 0.867), strong ion difference (P = 0.219), and mean renal artery flow velocity (P = 0.319) were similar. However, there was a significant increase in mean renal cortical tissue perfusion after PVR when compared with Voluven (P = 0.033). There was no difference in urinary neutrophil gelatinase-associated liopcalin to creatinine ratios after the infusion (P = 0.164). There was no difference in the blood volume-expanding properties of the 2 preparations of 6% hydroxyethyl starch. The balanced starch produced an increase in renal cortical tissue perfusion, a phenomenon not seen with starch in 0.9% saline.

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

PubMed

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

2013-07-01

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

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

Rapid engineering of endothelial cell-lined vascular-like structures in in situ crosslinkable hydrogels.

PubMed

Kageyama, Tatsuto; Kakegawa, Takahiro; Osaki, Tatsuya; Enomoto, Junko; Ito, Taichi; Nittami, Tadashi; Fukuda, Junji

2014-06-01

Fabrication of perfusable vascular networks in vitro is one of the most critical challenges in the advancement of tissue engineering. Because cells consume oxygen and nutrients during the fabrication process, a rapid fabrication approach is necessary to construct cell-dense vital tissues and organs, such as the liver. In this study, we propose a rapid molding process using an in situ crosslinkable hydrogel and electrochemical cell transfer for the fabrication of perfusable vascular structures. The in situ crosslinkable hydrogel was composed of hydrazide-modified gelatin (gelatin-ADH) and aldehyde-modified hyaluronic acid (HA-CHO). By simply mixing these two solutions, the gelation occurred in less than 20 s through the formation of a stable hydrazone bond. To rapidly transfer cells from a culture surface to the hydrogel, we utilized a zwitterionic oligopeptide, which forms a self-assembled molecular layer on a gold surface. Human umbilical vein endothelial cells adhering on a gold surface via the oligopeptide layer were transferred to the hydrogel within 5 min, along with electrochemical desorption of the oligopeptides. This approach was applicable to cylindrical needles 200-700 µm in diameter, resulting in the formation of perfusable microchannels where the internal surface was fully enveloped with the transferred endothelial cells. The entire fabrication process was completed within 10 min, including 20 s for the hydrogel crosslinking and 5 min for the electrochemical cell transfer. This rapid fabrication approach may provide a promising strategy to construct perfusable vasculatures in cell-dense tissue constructs and subsequently allow cells to organize complicated and fully vascularized tissues while preventing hypoxic cell injury.

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

PubMed Central

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

2011-01-01

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

Acidosis slows electrical conduction through the atrio-ventricular node

PubMed Central

Nisbet, Ashley M.; Burton, Francis L.; Walker, Nicola L.; Craig, Margaret A.; Cheng, Hongwei; Hancox, Jules C.; Orchard, Clive H.; Smith, Godfrey L.

2014-01-01

Acidosis affects the mechanical and electrical activity of mammalian hearts but comparatively little is known about its effects on the function of the atrio-ventricular node (AVN). In this study, the electrical activity of the epicardial surface of the left ventricle of isolated Langendorff-perfused rabbit hearts was examined using optical methods. Perfusion with hypercapnic Tyrode's solution (20% CO2, pH 6.7) increased the time of earliest activation (Tact) from 100.5 ± 7.9 to 166.1 ± 7.2 ms (n = 8) at a pacing cycle length (PCL) of 300 ms (37°C). Tact increased at shorter PCL, and the hypercapnic solution prolonged Tact further: at 150 ms PCL, Tact was prolonged from 131.0 ± 5.2 to 174.9 ± 16.3 ms. 2:1 AVN block was common at shorter cycle lengths. Atrial and ventricular conduction times were not significantly affected by the hypercapnic solution suggesting that the increased delay originated in the AVN. Isolated right atrial preparations were superfused with Tyrode's solutions at pH 7.4 (control), 6.8 and 6.3. Low pH prolonged the atrial-Hisian (AH) interval, the AVN effective and functional refractory periods and Wenckebach cycle length significantly. Complete AVN block occurred in 6 out of 9 preparations. Optical imaging of conduction at the AV junction revealed increased conduction delay in the region of the AVN, with less marked effects in atrial and ventricular tissue. Thus acidosis can dramatically prolong the AVN delay, and in combination with short cycle lengths, this can cause partial or complete AVN block and is therefore implicated in the development of brady-arrhythmias in conditions of local or systemic acidosis. PMID:25009505

Acidosis slows electrical conduction through the atrio-ventricular node.

PubMed

Nisbet, Ashley M; Burton, Francis L; Walker, Nicola L; Craig, Margaret A; Cheng, Hongwei; Hancox, Jules C; Orchard, Clive H; Smith, Godfrey L

2014-01-01

Acidosis affects the mechanical and electrical activity of mammalian hearts but comparatively little is known about its effects on the function of the atrio-ventricular node (AVN). In this study, the electrical activity of the epicardial surface of the left ventricle of isolated Langendorff-perfused rabbit hearts was examined using optical methods. Perfusion with hypercapnic Tyrode's solution (20% CO2, pH 6.7) increased the time of earliest activation (Tact) from 100.5 ± 7.9 to 166.1 ± 7.2 ms (n = 8) at a pacing cycle length (PCL) of 300 ms (37°C). Tact increased at shorter PCL, and the hypercapnic solution prolonged Tact further: at 150 ms PCL, Tact was prolonged from 131.0 ± 5.2 to 174.9 ± 16.3 ms. 2:1 AVN block was common at shorter cycle lengths. Atrial and ventricular conduction times were not significantly affected by the hypercapnic solution suggesting that the increased delay originated in the AVN. Isolated right atrial preparations were superfused with Tyrode's solutions at pH 7.4 (control), 6.8 and 6.3. Low pH prolonged the atrial-Hisian (AH) interval, the AVN effective and functional refractory periods and Wenckebach cycle length significantly. Complete AVN block occurred in 6 out of 9 preparations. Optical imaging of conduction at the AV junction revealed increased conduction delay in the region of the AVN, with less marked effects in atrial and ventricular tissue. Thus acidosis can dramatically prolong the AVN delay, and in combination with short cycle lengths, this can cause partial or complete AVN block and is therefore implicated in the development of brady-arrhythmias in conditions of local or systemic acidosis.

Automated Voxel-Based Analysis of Volumetric Dynamic Contrast-Enhanced CT Data Improves Measurement of Serial Changes in Tumor Vascular Biomarkers

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

Coolens, Catherine, E-mail: catherine.coolens@rmp.uhn.on.ca; Department of Radiation Oncology, University of Toronto, Toronto, Ontario; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario

2015-01-01

Objectives: Development of perfusion imaging as a biomarker requires more robust methodologies for quantification of tumor physiology that allow assessment of volumetric tumor heterogeneity over time. This study proposes a parametric method for automatically analyzing perfused tissue from volumetric dynamic contrast-enhanced (DCE) computed tomography (CT) scans and assesses whether this 4-dimensional (4D) DCE approach is more robust and accurate than conventional, region-of-interest (ROI)-based CT methods in quantifying tumor perfusion with preliminary evaluation in metastatic brain cancer. Methods and Materials: Functional parameter reproducibility and analysis of sensitivity to imaging resolution and arterial input function were evaluated in image sets acquired from amore » 320-slice CT with a controlled flow phantom and patients with brain metastases, whose treatments were planned for stereotactic radiation surgery and who consented to a research ethics board-approved prospective imaging biomarker study. A voxel-based temporal dynamic analysis (TDA) methodology was used at baseline, at day 7, and at day 20 after treatment. The ability to detect changes in kinetic parameter maps in clinical data sets was investigated for both 4D TDA and conventional 2D ROI-based analysis methods. Results: A total of 7 brain metastases in 3 patients were evaluated over the 3 time points. The 4D TDA method showed improved spatial efficacy and accuracy of perfusion parameters compared to ROI-based DCE analysis (P<.005), with a reproducibility error of less than 2% when tested with DCE phantom data. Clinically, changes in transfer constant from the blood plasma into the extracellular extravascular space (K{sub trans}) were seen when using TDA, with substantially smaller errors than the 2D method on both day 7 post radiation surgery (±13%; P<.05) and by day 20 (±12%; P<.04). Standard methods showed a decrease in K{sub trans} but with large uncertainty (111.6 ± 150.5) %. Conclusions: Parametric voxel-based analysis of 4D DCE CT data resulted in greater accuracy and reliability in measuring changes in perfusion CT-based kinetic metrics, which have the potential to be used as biomarkers in patients with metastatic brain cancer.« less

Automated Quantification of Myocardial Salvage in a Rat Model of Ischemia–Reperfusion Injury Using 3D High‐Resolution Magnetic Resonance Imaging (MRI)

PubMed Central

Grieve, Stuart M.; Mazhar, Jawad; Callaghan, Fraser; Kok, Cindy Y.; Tandy, Sarah; Bhindi, Ravinay; Figtree, Gemma A.

2014-01-01

Background Quantification of myocardial “area at risk” (AAR) and myocardial infarction (MI) zone is critical for assessing novel therapies targeting myocardial ischemia–reperfusion (IR) injury. Current “gold‐standard” methods perfuse the heart with Evan's Blue and stain with triphenyl tetrazolium chloride (TTC), requiring manual slicing and analysis. We aimed to develop and validate a high‐resolution 3‐dimensional (3D) magnetic resonance imaging (MRI) method for quantifying MI and AAR. Methods and Results Forty‐eight hours after IR was induced, rats were anesthetized and gadopentetate dimeglumine was administered intravenously. After 10 minutes, the coronary artery was re‐ligated and a solution containing iron oxide microparticles and Evan's Blue was infused (for comparison). Hearts were harvested and transversally sectioned for TTC staining. Ex vivo MR images of slices were acquired on a 9.4‐T magnet. T2* data allowed visualization of AAR, with microparticle‐associated signal loss in perfused regions. T1 data demonstrated gadolinium retention in infarcted zones. Close correlation (r=0.92 to 0.94; P<0.05) of MRI and Evan's Blue/TTC measures for both AAR and MI was observed when the combined techniques were applied to the same heart slice. However, 3D MRI acquisition and analysis of whole heart reduced intra‐observer variability compared to assessment of isolated slices, and allowed automated segmentation and analysis, thus reducing interobserver variation. Anatomical resolution of 81 μm3 was achieved (versus ≈2 mm with manual slicing). Conclusions This novel, yet simple, MRI technique allows precise assessment of infarct and AAR zones. It removes the need for tissue slicing and provides opportunity for 3D digital analysis at high anatomical resolution in a streamlined manner accessible for all laboratories already performing IR experiments. PMID:25146703

Metabolic profiling reveals that time related physiological changes in mammalian cell perfusion cultures are bioreactor scale independent.

PubMed

Vernardis, Spyros I; Goudar, Chetan T; Klapa, Maria I

2013-09-01

Metabolic profiling was used to characterize the time course of cell physiology both in laboratory- and manufacturing-scale mammalian cell perfusion cultures. Two independent experiments were performed involving three vials from the same BHK cell bank, used to inoculate three laboratory-scale bioreactors, from which four manufacturing-scale cultures were initiated. It was shown that metabolomic analysis can indeed enhance the prime variable dataset for the monitoring of perfusion cultures by providing a higher resolution view of the metabolic state. Metabolic profiles could capture physiological state shifts over the course of the perfusion cultures and indicated a metabolic "signature" of the phase transitions, which was not observable from prime variable data. Specifically, the vast majority of metabolites had lower concentrations in the middle compared to the other two phases. Notably, metabolomics provided orthogonal (to prime variables) evidence that all cultures followed this same metabolic state shift with cell age, independently of bioreactor scale. © 2013 Elsevier Inc. All rights reserved.

Sodium Chloride and Water Transport in the Medullary Thick Ascending Limb of Henle. EVIDENCE FOR ACTIVE CHLORIDE TRANSPORT

PubMed Central

Rocha, Antonino S.; Kokko, Juha P.

1973-01-01

Transport of NaCl and water was examined in the rabbit medullary thick ascending limb of Henle (ALH) by perfusing isolated segments of these nephrons in vitro. Osmotic water permeability was evaluated by perfusing tubules against imposed osmotic gradients. In these experiments the net transport of fluid remained at zero when segments of thick ALH were perfused with isotonic ultrafiltrate in a bath of rabbit serum in which the serum osmolality was increased by the addition of either 239±8 mosmol/liter of raffinose or 232±17 mosmol of NaCl indicating that the thick ascending limb of Henle is impermeant to osmotic flow of water. When these tubules were perfused at slow rates with isosmolal ultrafiltrate of same rabbit serum as used for the bath, the effluent osmolality was consistently lowered to concentrations less than the perfusate and the bath. That this decrease in collected fluid osmolality represented salt transport was demonstrated in a separate set of experiments in which it was shown that the sodium and chloride concentrations decreased to 0.79±0.02 and 0.77±0.02 respectively when compared with the perfusion fluid concentrations. In each instance the simultaneously determined transtubular potential difference (PD) revealed the lumen to be positive with the magnitude dependent on the perfusion rate. At flow rates above 2 nl·min-1, the mean transtubular PD was stable and equal to 6.70±0.34 mv. At stop-flow conditions this PD became more positive. Ouabain and cooling reversibly decreased the magnitude of this PD. The transtubular PD remained positive, 3.3±0.2 mV, when complete substitution of Na by choline was carried out in both the perfusion fluid and the bathing media. These results are interpreted to indicate that the active transport process is primarily an electrogenic chloride mechanism. The isotopic permeability coefficient for Na was 6.27±0.38 × 10-5 cm·s-1 indicating that the thick ALH is approximately as permeable to Na as the proximal convoluted tubule. The chloride permeability coefficient for the thick ALH was 1.06±0.12 × 10-5 cm·s-1 which is significantly less than the chloride permeability of the proximal tubule. These data demonstrate that the medullary thick ascending limb of Henle is water impermeable while having the capacity for active outward solute transport as a consequence of an electrogenic chloride pump. The combination of these characteristics allows this segment to generate a dilute tubular fluid and participate as the principal energy source for the overall operation of the countercurrent multiplication system. Images PMID:4685086

Bladder mucosa pH and Pco2 as a minimally invasive monitor of hemorrhagic shock and resuscitation.

PubMed

Clavijo-Alvarez, Julio A; Sims, Carrie A; Menconi, Michael; Shim, Inbo; Ochoa, Christian; Puyana, Juan Carlos

2004-12-01

Continuous monitoring of pH, Pco2, and Po2 using fiberoptic sensor technology has been proposed recently as a clinical monitor of the severity of shock and impaired tissue perfusion. Surrogates of gut tissue perfusion such as gastric tonometry, although cumbersome, have been used to indirectly quantify the degree of gut ischemia. The purpose of this study was to demonstrate the feasibility of monitoring bladder mucosa (BM) and to compare urinary bladder mucosa and proximal jejunum mucosa interstitial pH and Pco2 during hemorrhagic shock and resuscitation. Eleven male miniature swine (25-35 kg) (control, n = 4; shock, n = 7) underwent jejunal tonometry and cystostomy. A multisensor probe was placed adjacent to the BM. Urine was diverted. Normocarbia was maintained. Animals were hemorrhaged and kept at a mean arterial pressure of 40 mm Hg. When a constant infusion was required to maintain the mean arterial pressure at 40 mm Hg (decompensation), animals were resuscitated with shed blood plus two times the shed volume in lactated Ringer's solution (20 minutes) and observed for 2 hours. During decompensation, BM pH values decreased significantly from 7.33 +/- 0.08 to 7.01 +/- 0.2 (p < 0.01) and recovered to 7.11 +/- 0.19 at 120 minutes after completion of resuscitation. During decompensation, BM Pco2 values increased significantly compared with baseline (from 49 +/- 6 mm Hg to 71 +/- 19 mm Hg, p < 0.05) and returned to baseline with resuscitation. Jejunum mucosa and BM interstitial Pco2 correlated throughout shock and resuscitation (r = 0.49). Bland-Altman analysis demonstrated significant differences between jejunum mucosa (intramucosal pH) and BM interstitial pH. Shock-induced changes in the Pco2 of the BM are comparable to tonometric changes in the gut. These data suggest that continuous fiberoptic multisensor probe monitoring of the BM could potentially provide a minimally invasive method for the assessment of impaired tissue perfusion of the splanchnic circulation during shock and resuscitation.

Fully automated registration of first-pass myocardial perfusion MRI using independent component analysis.

PubMed

Milles, J; van der Geest, R J; Jerosch-Herold, M; Reiber, J H C; Lelieveldt, B P F

2007-01-01

This paper presents a novel method for registration of cardiac perfusion MRI. The presented method successfully corrects for breathing motion without any manual interaction using Independent Component Analysis to extract physiologically relevant features together with their time-intensity behavior. A time-varying reference image mimicking intensity changes in the data of interest is computed based on the results of ICA, and used to compute the displacement caused by breathing for each frame. Qualitative and quantitative validation of the method is carried out using 46 clinical quality, short-axis, perfusion MR datasets comprising 100 images each. Validation experiments showed a reduction of the average LV motion from 1.26+/-0.87 to 0.64+/-0.46 pixels. Time-intensity curves are also improved after registration with an average error reduced from 2.65+/-7.89% to 0.87+/-3.88% between registered data and manual gold standard. We conclude that this fully automatic ICA-based method shows an excellent accuracy, robustness and computation speed, adequate for use in a clinical environment.

No evidence of perfusion abnormalities in the basal ganglia of a patient with generalized chorea-ballism and polycythaemia vera: analysis using subtraction SPECT co-registered to MRI.

PubMed

Kim, Woojun; Kim, Joong-Seok; Lee, Kwang-Soo; Kim, Yeong-In; Park, Chong-Won; Chung, Yong-An

2008-10-01

Polycythaemia vera is a well-known cause of symptomatic chorea, however, the pathophysiology of this correlation remains unclear. We report on a patient with generalized chorea-ballism associated with polycythaemia vera, and we present the findings of 99mTc-hexamethylpropylene amine oxime (HMPAO) SPECT done in both the choreic state and the non-choreic state. The SPECT during both the choreic and the non-choreic states did not reveal any definite perfusion changes in specific regions of the brain, as compared with 6 age-matched controls. In addition, the subtraction SPECT co-registered to MRI (SISCOM) analysis did not show any difference in cerebral blood flow during the choreic and non-choreic states. This result suggests that the basic mechanism of chorea associated with polycythaemia vera does not appear to be associated with a reduction in cerebral perfusion to a specific cerebral area, such as the basal ganglia or its thalamocortical connections.

Microvascular perfusion during focal vasogenic brain edema: a scanning laser fluorescence microscopy study.

PubMed

Lindsberg, P J; Sirén, A L; Hallenbeck, J M

1997-01-01

Controversy exists about the effect of tissue edema on cerebral microcirculation. High spatial resolution is required for observation of extravasation and microcirculation during focal vasogenic edema formation. To study the relationship between tissue edema and perfusion, we developed a technique for simultaneous visualization of extravasation and microvessel perfusion in rats. Focal intracortical microvascular injury was generated with a 1-sec Nd-YAG laser pulse. Evans blue albumin (EBA) was infused 30 min before decapitation to study extravasation and FITC-dextran was injected 30 sec prior to decapitation to examine microvessel perfusion. Computerized scanning laser-excited fluorescence microscopy followed by high resolution image analysis permitted quantitative assessment of both parameters on single fresh-frozen brain sections. Studied at 30 min (3.66 +/- 0.15 mm), 2 hr (4.14 +/- 0.08 mm, P < .05), and 8 hr (4.69 +/- 0.18 mm, P < .01) after injury, the diameter of the circular, sharply demarcated zone of EBA-extravasation increased progressively. At 30 min, microvessels at a zone surrounding the area of EBA-extravasation contained 69 +/- 14% (P < .05) more fluorescent FITC-filling than in the control hemisphere, but the density of perfused microvessels was unchanged. At 2 hr, secondary tissue changes had already occurred in a zone surrounding the initial laser lesion. While severe reduction in the density (-76 +/- 13%, P < .05) of perfused microvessels was observed within 400 to 240 microm inside the border of EBA extravasation, perfusion indexes were normal despite the presence of extravasated plasma constituents within 0-80 microm from the border. In a narrow zone (80 microm) outside the border of extravasation, individual microvessels contained 34 +/- 9% (P < .01) less FITC-fluorescence than those in a homologous area of the uninjured contralateral hemisphere. This report demonstrates the feasibility of simultaneous measurement and high-resolution mapping of indices of microvascular perfusion (density, filling) and extravasated plasma constituents in damaged and intact brain areas. In this model, the presence of extravasated plasma constituents the size of proteins did not immediately influence indices of cortical microcirculation. However, microvascular perfusion may be perturbed surrounding such an area of advancing vasogenic edema formation.

What's behind the mask? A look at blood flow changes with prolonged facial pressure and expression using laser Doppler imaging.

PubMed

Van-Buendia, Lan B; Allely, Rebekah R; Lassiter, Ronald; Weinand, Christian; Jordan, Marion H; Jeng, James C

2010-01-01

Clinically, the initial blanching in burn scar seen on transparent plastic face mask application seems to diminish with time and movement requiring mask alteration. To date, studies quantifying perfusion with prolonged mask use do not exist. This study used laser Doppler imaging (LDI) to assess perfusion through the transparent face mask and movement in subjects with and without burn over time. Five subjects fitted with transparent face masks were scanned with the LDI on four occasions. The four subjects without burn were scanned in the following manner: 1) no mask, 2) mask on while at rest, 3) mask on with alternating intervals of sustained facial expression and rest, and 4) after mask removal. Images were acquired every 3 minutes throughout the 85-minute study period. The subject with burn underwent a shortened scanning protocol to increase comfort. Each face was divided into five regions of interest for analysis. Compared with baseline, mask application decreased perfusion significantly in all subjects (P < .0001). Perfusion did not change during the rest period. There were no significant differences with changing facial expression in any of the regions of interest. On mask removal, all regions of the face demonstrated a hyperemic effect with the chin (P = .05) and each cheek (P < .0001) reaching statistical significance. Perfusion levels did not return to baseline in the chin and cheeks after 30 minutes of mask removal. Perfusions remain constantly low while wearing the face mask, despite changing facial expressions. Changing facial expressions with the mask on did not alter perfusion. Hyperemic response occurs on removal of the mask. This study exposed methodology and statistical issues worth considering when conducting future research with the face, pressure therapy, and with LDI technology.

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

PubMed Central

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

2014-01-01

Background The basic strategy to construct tissue engineered bone graft (TEBG) is to combine osteoblastic cells with three dimensional (3D) scaffold. Based on this strategy, we proposed the “Totally Vitalized TEBG” (TV-TEBG) which was characterized by abundant and homogenously distributed cells with enhanced cell proliferation and differentiation and further investigated its biological performance in repairing segmental bone defect. Methods In this study, we constructed the TV-TEBG with the combination of customized flow perfusion seeding/culture system and β-tricalcium phosphate (β-TCP) scaffold fabricated by Rapid Prototyping (RP) technique. We systemically compared three kinds of TEBG constructed by perfusion seeding and perfusion culture (PSPC) method, static seeding and perfusion culture (SSPC) method, and static seeding and static culture (SSSC) method for their in vitro performance and bone defect healing efficacy with a rabbit model. Results Our study has demonstrated that TEBG constructed by PSPC method exhibited better biological properties with higher daily D-glucose consumption, increased cell proliferation and differentiation, and better cell distribution, indicating the successful construction of TV-TEBG. After implanted into rabbit radius defects for 12 weeks, PSPC group exerted higher X-ray score close to autograft, much greater mechanical property evidenced by the biomechanical testing and significantly higher new bone formation as shown by histological analysis compared with the other two groups, and eventually obtained favorable healing efficacy of the segmental bone defect that was the closest to autograft transplantation. Conclusion This study demonstrated the feasibility of TV-TEBG construction with combination of perfusion seeding, perfusion culture and RP technique which exerted excellent biological properties. The application of TV-TEBG may become a preferred candidate for segmental bone defect repair in orthopedic and maxillofacial fields. PMID:24728277

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 of NFL players.

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.

Stem cells enhance reperfusion following ischemia: Validation using laser speckle imaging in predicting tissue repair.

PubMed

Tang, Ya Hui; Thompson, R Will; Nathan, Cherie-Ann; Alexander, Jonathan Steven; Lian, Timothy

2018-06-01

The lack of real-time assessment of vascular perfusion changes remains a major weakness in assessing the efficacy of bone marrow stromal cells (BMSC) therapeutic ischemia reperfusion (I/R) injury. This study provides for the first time the real-time in vivo perfusion monitoring in I/R mice with BMSC therapy. Animal model. Surgically created cutaneous flaps perfused by the inferior epigastric vessels were subjected to 3.5 hours of ischemia/reperfusion. Wound healing and vascular perfusion were assessed by Image-J and laser speckle contrast analysis (LSCA) in three groups (sham, I/R, and I/R + BMSC). BMSC tracking was quantified in an additional two groups (with/without I/R) using intravital fluorescent microscopy. The histopathology of skin flaps was examined by hematoxylin and eosin stain. Infiltrated macrophages were analyzed by confocal immunofluorescent microscopy. Postischemic tissues treated with BMSC demonstrated significantly greater survival than I/R control. On days 3 to 7 postreperfusion, both proximal and distal areas in BMSC-treated flaps demonstrated greater levels of perfusion than untreated I/R flaps (P < 0.05). Intravital fluorescent microscopy revealed that numbers of labeled BMSC were significantly increased in the distal area compared to the proximal area in both with and without ischemic mice. Histological examination showed lower necrosis and infiltrated inflammatory cells in I/R + BMSC-treated mice versus I/R controls. BMSC accumulated in I/R flaps and exerted beneficial effects including: 1) improving vascular perfusion and 2) attenuating inflammatory cell infiltration. LSCA facilitates monitoring of the real-time restitution of perfusion during flap wound healing in experimental animals and could also similarly applied in clinical investigations. NA. Laryngoscope, 128:E198-E205, 2018. © 2018 The American Laryngological, Rhinological and Otological Society, Inc.

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 study carries implications for the neurological safety of NFL players. PMID:27128374

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

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.

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 pregnancies at-risk for vascular insufficiency; early recognition may facilitate intervention and improved pregnancy outcomes. PMID:26928151

Design and testing of an endoscopic photoacoustic probe for determination of treatment depth after photodynamic therapy

NASA Astrophysics Data System (ADS)

Viator, John A.; Paltauf, Guenther; Jacques, Steven L.; Prahl, Scott A.

2001-06-01

An endoscopic photoacoustic probe is designed and tested for use in PDT treatment of esophageal cancer. The probe, measuring less than 2.5 mm in diameter, was designed to fit within the lumen of an endoscope that will be inserted into an esophagus after PDT. PDT treatment results in a blanched, necrotic layer of cancerous tissue over a healthy, deeper layer of perfused tissue. The photoacoustic probe was designed to use acoustic propagation time to determine the thickness of the blanched surface of the esophagus, which corresponds to treatment depth. A side-firing 600 micrometers fiber delivered 532 nm laser light to induce acoustic waves in the perfused layer of the esophagus beneath the blanched (treated) layer. A PVDF transducer detected the induced acoustic waves and transmitted the signal to an oscilloscope. The probe was tested on clear and turbid tissue phantom layers over an optically absorbing dye solution.

Application of differential interference contrast with inverted microscopes to the in vitro perfused nephron.

PubMed

Horster, M; Gundlach, H

1979-12-01

The study of in vitro perfused individual nephron segments requires a microscope which provides: (1) easy access to the specimen for measurement of cellular solute flux and voltage; (2) an image with high resolution and contrast; (3) optical sectioning of the object at different levels; and (4) rapid recording of the morphological phenomena. This paper describes an example of commercially available apparatus meeting the above requirements, and illustrates its efficiency. The microscope is of the inverted type (Zeiss IM 35) equipped with differential-interference-contrast (DIC) with a long working distance, and an automatically controlled camera system. The microscopic image exhibits cellular and intercellular details in the unstained transporting mammalian nephron segments despite their tubular structure and great thickness and makes obvious function-structure correlations (e.g. cell volume changes); luminal and contraluminal cell borders are well resolved for controlled microelectrode impalement.

Pulmonary Perfusion Changes as Assessed by Contrast-Enhanced Dual-Energy Computed Tomography after Endoscopic Lung Volume Reduction by Coils.

PubMed

Lador, Frédéric; Hachulla, Anne-Lise; Hohn, Olivia; Plojoux, Jérôme; Ronot, Maxime; Montet, Xavier; Soccal, Paola M

2016-01-01

Endoscopic lung volume reduction by coils (LVRC) is a recent treatment approach for severe emphysema. Furthermore, dual-energy computed tomography (DECT) now offers a combined assessment of lung morphology and pulmonary perfusion. The aim of our study was to assess the impact of LVRC on pulmonary perfusion with DECT. Seventeen patients (64.8 ± 6.7 years) underwent LVRC. DECT was performed prior to and after LVRC. For each patient, lung volumes and emphysema quantification were automatically calculated. Then, 6 regions of interest (ROIs) on the iodine perfusion map were drawn in the anterior, mid, and posterior right and left lungs at 4 defined levels. The ROI values were averaged to obtain lung perfusion as assessed by the lung's iodine concentration (CLung, μg·cm-3). The CLung values were normalized using the left atrial iodine concentration (CLA) to take into account differences between successive DECT scans. The 6-min walk distance (6MWD) improved significantly after the procedure (p = 0.0002). No lung volume changes were observed between successive DECT scans for any of the patients (p = 0.32), attesting the same suspended inspiration. After LVRC, the emphysema index was significantly reduced in the treated lung (p = 0.0014). Lung perfusion increased significantly adjacent to the treated areas (CLung/CLA from 3.4 ± 1.7 to 5.6 ± 2.2, p < 0.001) and in the ipsilateral untreated areas (from 4.1 ± 1.4 to 6.6 ± 1.7, p < 0.001), corresponding to a mean 65 and 61% increase in perfusion, respectively. No significant difference was observed in the contralateral upper and lower areas (from 4.4 ± 1.9 to 4.8 ± 2.1, p = 0.273, and from 4.9 ± 2.0 to 5.2 ± 1.7, p = 0.412, respectively). A significant correlation between increased 6MWD and increased perfusion was found (p = 0.0027, R2 = 0.3850). Quantitative analysis based on DECT acquisition revealed that LVRC results in a significant increase in perfusion in the coil-free areas adjacent to the treated ones, as well as in the ipsilateral untreated areas. This suggests a possible role for LVRC in the improvement of the ventilation/perfusion relationship. © 2016 S. Karger AG, Basel.

Investigation of styrene in the liver perfusion/cell culture system. No indication of styrene-7,8-oxide as the principal mutagenic metabolite produced by the intact rat liver.

PubMed

Beije, B; Jenssen, D

1982-03-01

Mutagenic effect of styrene and styrene-7,8-oxide was studied with the isolated perfused rat liver as metabolizing system and Chinese hamster V79 cells as genetic target cells. Styrene-7,8-oxide which is mutagenic per se was rapidly metabolized by the perfused rat liver. Thus no mutagenic effect was detected neither in the perfusion medium nor in the bile. However when styrene was added to the perfusion system, an increase in V79 mutants was observed regardless of where in the circulating perfusion medium the V79 cells were placed: the same effect was obtained with V79 cells close to the liver as well as at a distance from the liver. No mutagenic effect was observed in the bile. Simultaneous analysis of the styrene-7,8-oxide concentration in the perfusion medium, suggest that this metabolite is not the cause of the mutagenic effect observed during perfusion with styrene. The effect of the two test compounds on some liver functions was also studied. Both styrene and styrene-7,8-oxide changed the bile flow without affecting bile acid secretion: styrene caused a reduction in bile flow as compared to control perfusions and styrene-7,8-oxide increased the bile flow. Styrene, but not styrene-7,8-oxide, reduced gluconeogenesis from lactate. Styrene had no effect on the liver's capacity to incorporate amino acids into plasma proteins, whereas styrene-7,8-oxide reduced the amino acid incorporation. The microsomal cytochrome P-450 content was not affected by the two test compounds. No alteration in microsomal N- and C-oxygenation of N,N-dimethylaniline (DMA) was observed with styrene-7,8-oxide or the lower styrene dose used (240 mumol), whereas the higher styrene concentration (480 mumol) reduced N-oxygenation and thus also the total DNA metabolism. It is suggested that the results on styrene and styrene-7,8-oxide found here using the liver perfusion/cell culture system mimic the metabolism expected to be found in the intact animal, thus indicating that styrene-7,8-oxide is not the principal mutagenic metabolite of styrene in vivo.

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 ...

Perfusion MRI in Early Stage of Legg-Calvé-Perthes Disease to Predict Lateral Pillar Involvement: A Preliminary Study.

PubMed

Kim, Harry K W; Wiesman, Kathryn D; Kulkarni, Vedant; Burgess, Jamie; Chen, Elena; Brabham, Case; Ikram, Haseeb; Du, Jerry; Lu, Amanda; Kulkarni, Ashok V; Dempsey, Molly; Herring, J Anthony

2014-07-16

Current radiographic classifications for Legg-Calvé-Perthes disease cannot be applied at the early stages of the disease. The purpose of this study was to quantify the perfusion of the femoral epiphysis in the early stages of Legg-Calvé-Perthes disease with use of perfusion magnetic resonance imaging (MRI) and to determine if the extent of epiphyseal perfusion can predict the lateral pillar involvement at the mid-fragmentation stage. Twenty-nine patients had gadolinium-enhanced perfusion MRI at the initial stage or early fragmentation stage of Legg-Calvé-Perthes disease and were followed prospectively. The percent perfusion of the whole epiphysis and its lateral third was measured by four independent observers using image analysis software. The radiographs obtained at the mid-fragmentation stage were used for the lateral pillar classification. Intraclass correlation coefficient (ICC) and logistic regression analyses were performed. The mean age (and standard deviation) at diagnosis was 7.7 ± 1.7 years (range, 5.3 to 11.3 years). The mean interval between the MRI and the time of maximum fragmentation was 8.2 ± 5.5 months. The interobserver ICC for the percent perfusion of the lateral third of the epiphysis was 0.90 (95% confidence interval [CI]: 0.83 to 0.95). The mean percent perfusion of the lateral third of the epiphysis was 92% ± 2%, 68% ± 18%, and 46% ± 12% for the hips in which the lateral pillar was later classified as A, B, and C, respectively (p = 0.001). When the perfusion level was ≥90% in the lateral third of the epiphysis, the odds ratio of the lateral pillar being later classified as group A, as opposed to B or C, was 72.0 (CI: 3.5 to 1476). With a perfusion level of ≤55% in the lateral third of the epiphysis, the odds ratio of the lateral pillar being later classified as group C, as opposed to A or B, was 33.3 (CI: 2.8 to 392). Similar results were obtained for the whole epiphysis. Perfusion MRI measurements of the total epiphysis and its lateral third obtained at the early stages of Legg-Calvé-Perthes disease were predictive of lateral pillar involvement at the mid-fragmentation stage of the disease. Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence. Copyright © 2014 by The Journal of Bone and Joint Surgery, Incorporated.

Simultaneous Assessment of Myocardial Perfusion, Wall Motion, and Deformation during Myocardial Contrast Echocardiography: A Feasibility Study.

PubMed

Zoppellaro, Giacomo; Venneri, Lucia; Khattar, Rajdeep S; Li, Wei; Senior, Roxy

2016-06-01

Ultrasound contrast agents may be used for the assessment of regional wall motion and myocardial perfusion, but are generally considered not suitable for deformation analysis. The aim of our study was to assess the feasibility of deformation imaging on contrast-enhanced images using a novel methodology. We prospectively enrolled 40 patients who underwent stress echocardiography with continuous intravenous infusion of SonoVue for the assessment of myocardial perfusion imaging with flash replenishment technique. We compared longitudinal strain (Lε) values, assessed with a vendor-independent software (2D CPA), on 68 resting contrast-enhanced and 68 resting noncontrast recordings. Strain analysis on contrast recordings was evaluated in the first cardiac cycles after the flash. Tracking of contrast images was deemed feasible in all subjects and in all views. Contrast administration improved image quality and increased the number of segments used for deformation analysis. Lε of noncontrast and contrast-enhanced images were statistically different (-18.8 ± 4.5% and -22.8 ± 5.4%, respectively; P < 0.001), but their correlation was good (ICC 0.65, 95%CI 0.42-0.78). Patients with resting wall-motion abnormalities showed lower Lε values on contrast recordings (-18.6 ± 6.0% vs. -24.2 ± 5.5%, respectively; P < 0.01). Intra-operator and inter-operator reproducibility was good for both noncontrast and contrast images with no statistical differences. Our study shows that deformation analysis on postflash contrast-enhanced images is feasible and reproducible. Therefore, it would be possible to perform a simultaneous evaluation of wall-motion abnormalities, volumes, ejection fraction, perfusion defects, and cardiac deformation on the same contrast recording. © 2016, Wiley Periodicals, Inc.

An open source software for analysis of dynamic contrast enhanced magnetic resonance images: UMMPerfusion revisited.

PubMed

Zöllner, Frank G; Daab, Markus; Sourbron, Steven P; Schad, Lothar R; Schoenberg, Stefan O; Weisser, Gerald

2016-01-14

Perfusion imaging has become an important image based tool to derive the physiological information in various applications, like tumor diagnostics and therapy, stroke, (cardio-) vascular diseases, or functional assessment of organs. However, even after 20 years of intense research in this field, perfusion imaging still remains a research tool without a broad clinical usage. One problem is the lack of standardization in technical aspects which have to be considered for successful quantitative evaluation; the second problem is a lack of tools that allow a direct integration into the diagnostic workflow in radiology. Five compartment models, namely, a one compartment model (1CP), a two compartment exchange (2CXM), a two compartment uptake model (2CUM), a two compartment filtration model (2FM) and eventually the extended Toft's model (ETM) were implemented as plugin for the DICOM workstation OsiriX. Moreover, the plugin has a clean graphical user interface and provides means for quality management during the perfusion data analysis. Based on reference test data, the implementation was validated against a reference implementation. No differences were found in the calculated parameters. We developed open source software to analyse DCE-MRI perfusion data. The software is designed as plugin for the DICOM Workstation OsiriX. It features a clean GUI and provides a simple workflow for data analysis while it could also be seen as a toolbox providing an implementation of several recent compartment models to be applied in research tasks. Integration into the infrastructure of a radiology department is given via OsiriX. Results can be saved automatically and reports generated automatically during data analysis ensure certain quality control.

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

Selective cerebral perfusion prevents abnormalities in glutamate cycling and neuronal apoptosis in a model of infant deep hypothermic circulatory arrest and reperfusion.

PubMed

Kajimoto, Masaki; Ledee, Dolena R; Olson, Aaron K; Isern, Nancy G; Robillard-Frayne, Isabelle; Des Rosiers, Christine; Portman, Michael A

2016-11-01

Deep hypothermic circulatory arrest is often required for the repair of complex congenital cardiac defects in infants. However, deep hypothermic circulatory arrest induces neuroapoptosis associated with later development of neurocognitive abnormalities. Selective cerebral perfusion theoretically provides superior neural protection possibly through modifications in cerebral substrate oxidation and closely integrated glutamate cycling. We tested the hypothesis that selective cerebral perfusion modulates glucose utilization, and ameliorates abnormalities in glutamate flux, which occur in association with neuroapoptosis during deep hypothermic circulatory arrest. Eighteen infant male Yorkshire piglets were assigned randomly to two groups of seven (deep hypothermic circulatory arrest or deep hypothermic circulatory arrest with selective cerebral perfusion for 60 minutes at 18℃) and four control pigs without cardiopulmonary bypass support. Carbon-13-labeled glucose as a metabolic tracer was infused, and gas chromatography-mass spectrometry and nuclear magnetic resonance were used for metabolic analysis in the frontal cortex. Following 2.5 h of cerebral reperfusion, we observed similar cerebral adenosine triphosphate levels, absolute levels of lactate and citric acid cycle intermediates, and carbon-13 enrichment among three groups. However, deep hypothermic circulatory arrest induced significant abnormalities in glutamate cycling resulting in reduced glutamate/glutamine and elevated γ-aminobutyric acid/glutamate along with neuroapoptosis, which were all prevented by selective cerebral perfusion. The data suggest that selective cerebral perfusion prevents these modifications in glutamate/glutamine/γ-aminobutyric acid cycling and protects the cerebral cortex from apoptosis. © The Author(s) 2016.

DCEUS-based focal parametric perfusion imaging of microvessel with single-pixel resolution and high contrast.

PubMed

Wang, Diya; Xiao, Mengnan; Hu, Hong; Zhang, Yu; Su, Zhe; Xu, Shanshan; Zong, Yujin; Wan, Mingxi

2018-03-01

This study aimed to develop a focal microvascular contrast-enhanced ultrasonic parametric perfusion imaging (PPI) scheme to overcome the tradeoff between the resolution, contrast, and accuracy of focal PPI in the tumor. Its resolution was limited by the low signal-to-clutter ratio (SCR) of time-intensity-curves (TICs) induced by multiple limitations, which deteriorated the accuracy and contrast of focal PPI. The scheme was verified by the in-vivo perfusion experiments. Single-pixel TICs were first extracted to ensure PPI with the highest resolution. The SCR of focal TICs in the tumor was improved using respiratory motion compensation combined with detrended fluctuation analysis. The entire and focal PPIs of six perfusion parameters were then accurately created after filtrating the valid TICs and targeted perfusion parameters. Compared with those of the conventional PPIs, the axial and lateral resolutions of focal PPIs were improved by 30.29% (p < .05) and 32.77% (p < .05), respectively; the average contrast and accuracy evaluated by SCR improved by 7.24 ± 4.90 dB (p < .05) and 5.18 ± 1.28 dB (p < .05), respectively. The edge, morphostructure, inhomogeneous hyper-enhanced distribution, and ring-like perfusion features in intratumoral microvessel were accurately distinguished and highlighted by the focal PPIs. The developed focal PPI can assist clinicians in making confirmed diagnoses and in providing appropriate therapeutic strategies for liver tumor. Copyright © 2017 Elsevier B.V. All rights reserved.

Geographic and demographic variabilities of quantitative parameters in stress myocardial computed tomography perfusion.

PubMed

Park, Jinoh; Kim, Hyun-Sook; Hwang, Hye Jeon; Yang, Dong Hyun; Koo, Hyun Jung; Kang, Joon-Won; Kim, Young-Hak

2017-09-01

To evaluate the geographic and demographic variabilities of the quantitative parameters of computed tomography perfusion (CTP) of the left ventricular (LV) myocardium in patients with normal coronary artery on computed tomography angiography (CTA). From a multicenter CTP registry of stress and static computed tomography, we retrospectively recruited 113 patients (mean age, 60 years; 57 men) without perfusion defect on visual assessment and minimal (< 20% of diameter stenosis) or no coronary artery disease on CTA. Using semiautomatic analysis software, quantitative parameters of the LV myocardium, including the myocardial attenuation in stress and rest phases, transmural perfusion ratio (TPR), and myocardial perfusion reserve index (MPRI), were evaluated in 16 myocardial segments. In the lateral wall of the LV myocardium, all quantitative parameters except for MPRI were significantly higher compared with those in the other walls. The MPRI showed consistent values in all myocardial walls (anterior to lateral wall: range, 25% to 27%; p = 0.401). At the basal level of the myocardium, all quantitative parameters were significantly lower than those at the mid- and apical levels. Compared with men, women had significantly higher values of myocardial attenuation and TPR. Age, body mass index, and Framingham risk score were significantly associated with the difference in myocardial attenuation. Geographic and demographic variabilities of quantitative parameters in stress myocardial CTP exist in healthy subjects without significant coronary artery disease. This information may be helpful when assessing myocardial perfusion defects in CTP.

Influence of amplitude-related perfusion parameters in the parotid glands by non-fat-saturated dynamic contrast-enhanced magnetic resonance imaging

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

Chiu, Su-Chin; Cheng, Cheng-Chieh; Chang, Hing-Chiu

Purpose: To verify whether quantification of parotid perfusion is affected by fat signals on non-fat-saturated (NFS) dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and whether the influence of fat is reduced with fat saturation (FS). Methods: This study consisted of three parts. First, a retrospective study analyzed DCE-MRI data previously acquired on different patients using NFS (n = 18) or FS (n = 18) scans. Second, a phantom study simulated the signal enhancements in the presence of gadolinium contrast agent at six concentrations and three fat contents. Finally, a prospective study recruited nine healthy volunteers to investigate the influence of fatmore » suppression on perfusion quantification on the same subjects. Parotid perfusion parameters were derived from NFS and FS DCE-MRI data using both pharmacokinetic model analysis and semiquantitative parametric analysis. T tests and linear regression analysis were used for statistical analysis with correction for multiple comparisons. Results: NFS scans showed lower amplitude-related parameters, including parameter A, peak enhancement (PE), and slope than FS scans in the patients (all with P < 0.0167). The relative signal enhancement in the phantoms was proportional to the dose of contrast agent and was lower in NFS scans than in FS scans. The volunteer study showed lower parameter A (6.75 ± 2.38 a.u.), PE (42.12% ± 14.87%), and slope (1.43% ± 0.54% s{sup −1}) in NFS scans as compared to 17.63 ± 8.56 a.u., 104.22% ± 25.15%, and 9.68% ± 1.67% s{sup −1}, respectively, in FS scans (all with P < 0.005). These amplitude-related parameters were negatively associated with the fat content in NFS scans only (all with P < 0.05). Conclusions: On NFS DCE-MRI, quantification of parotid perfusion is adversely affected by the presence of fat signals for all amplitude-related parameters. The influence could be reduced on FS scans.« less

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 lesions among all the parameters. Copyright © 2018. Published by Elsevier Masson SAS.

Biliary secretion of fluid-phase markers by the isolated perfused rat liver. Role of transcellular vesicular transport.

PubMed Central

Lake, J R; Licko, V; Van Dyke, R W; Scharschmidt, B F

1985-01-01

In these studies, we have used several approaches to systematically explore the contribution of transcellular vesicular transport (transcytosis) to the blood-to-bile movement of inert fluid-phase markers of widely varying molecular weight. First, under steady-state conditions, the perfused rat liver secreted even large markers in appreciable amounts. The bile-to-plasma (B/P) ratio of these different markers, including microperoxidase (B/P ratio = 0.06; mol wt = 1,879), insulin (B/P ratio = 0.09, mol wt = 5,000), horseradish peroxidase (B/P ratio = 0.04, mol wt = 40,000), and dextran (B/P ratio = 0.09, mol wt = 70,000), exhibited no clear ordering based on size alone, and when dextrans of two different sizes (40,000 and 70,000 mol wt) were studied simultaneously, the relative amounts of the two dextran species in bile were the same as in perfusate. Taurocholate administration produced a 71% increase in bile flow but little or no (0-20%) increase in the output of horseradish peroxidase, microperoxidase, inulin, and dextran. Second, under nonsteady-state conditions in which the appearance in or disappearance from bile of selected markers was studied after their abrupt addition to or removal from perfusate, erythritol reached a B/P ratio of 1 within 2 min. Microperoxidase and dextran appeared in bile only after a lag period of approximately 12 min and then slowly approached maximal values, whereas sucrose exhibited kinetically intermediate behavior. A similar pattern was observed after removal of greater than 95% of the marker from the perfusate. Erythritol rapidly reapproached a B/P ratio of 1, whereas the B/P ratio for sucrose, dextran, and microperoxidase fell much more slowly and exceeded 1 for a full 30 min after perfusate washout. Finally, electron microscopy and fluorescence microscopy of cultured hepatocytes demonstrated the presence of horseradish peroxidase and fluorescein-dextran, respectively, in intracellular vesicles, and fractionation of perfused liver homogenates revealed that at least 35-50% of sucrose, inulin, and dextran was associated with subcellular organelles. Collectively, these observations are most compatible with a transcytosis pathway that contributes minimally to the secretion of erythritol, but accounts for a substantial fraction of sucrose secretion and virtually all (greater than 95%) of the blood-to-bile transport of microperoxidase and larger markers. These findings have important implications with respect to current concepts of canalicular bile formation as well as with respect to the conventional use of solutes such as sucrose as markers of canalicular or paracellular pathway permeability. Images PMID:2411761

Novel cardiac protective effects of urea: from shark to rat

PubMed Central

Wang, Xintao; Wu, Lingyun; Aouffen, M'hamed; Mateescu, Mircea-Alexandru; Nadeau, Réginald; Wang, Rui

1999-01-01

This study was carried out to investigate novel cardioprotective effects of urea and the underlying mechanisms. The cardiac functions under oxidative stress were evaluated using Langendorff perfused isolated heart.Isolated dogfish shark hearts tolerated the oxidative stress generated by electrolysis (10 mA, 1 min) of the perfusion solution (n=4), and also showed normal cardiac functions during post-ischaemia reperfusion (n=4). The high concentration of urea (350 mM) in the heart perfusate was indispensable for maintaining the normal cardiac functions of the shark heart.Urea at 3–300 mM (n=4 for each group) protected the isolated rat heart against both electrolysis-induced heart damage and post-ischaemia reperfusion-induced cardiac injury.A concentration-dependent scavenging effect of urea (3–300 mM, n=4 for each group) against electrolysis-induced reactive oxygen species was also demonstrated in vitro.Urea derivatives as hydroxyurea, dimethylurea, and thiourea had antioxidant cardioprotective effect against the electrolysis-induced cardiac dysfunction of rat heart, but were not as effective as urea in suppressing the post-ischaemia reperfusion injury.Our results suggest that urea and its derivatives are potential antioxidant cardioprotective agents against oxidative stress-induced myocardium damage including the post-ischaemia reperfusion-induced injury. PMID:10602326

Additively Manufactured Device for Dynamic Culture of Large Arrays of 3D Tissue Engineered Constructs.

PubMed

Costa, Pedro F; Hutmacher, Dietmar W; Theodoropoulos, Christina; Gomes, Manuela E; Reis, Rui L; Vaquette, Cédryck

2015-04-22

The ability to test large arrays of cell and biomaterial combinations in 3D environments is still rather limited in the context of tissue engineering and regenerative medicine. This limitation can be generally addressed by employing highly automated and reproducible methodologies. This study reports on the development of a highly versatile and upscalable method based on additive manufacturing for the fabrication of arrays of scaffolds, which are enclosed into individualized perfusion chambers. Devices containing eight scaffolds and their corresponding bioreactor chambers are simultaneously fabricated utilizing a dual extrusion additive manufacturing system. To demonstrate the versatility of the concept, the scaffolds, while enclosed into the device, are subsequently surface-coated with a biomimetic calcium phosphate layer by perfusion with simulated body fluid solution. 96 scaffolds are simultaneously seeded and cultured with human osteoblasts under highly controlled bidirectional perfusion dynamic conditions over 4 weeks. Both coated and noncoated resulting scaffolds show homogeneous cell distribution and high cell viability throughout the 4 weeks culture period and CaP-coated scaffolds result in a significantly increased cell number. The methodology developed in this work exemplifies the applicability of additive manufacturing as a tool for further automation of studies in the field of tissue engineering and regenerative medicine. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Endothelial cell membrane vesicles in the study of organ preference of metastasis.

PubMed

Johnson, R C; Augustin-Voss, H G; Zhu, D Z; Pauli, B U

1991-01-01

Many malignancies exhibit distinct patterns of metastasis that appear to be mediated by receptor/ligand-like interactions between tumor cells and organ-specific vascular endothelium. In order to study endothelial cell surface molecules involved in the binding of metastatic cells, we developed a perfusion method to isolate outside-out membrane vesicles from the lumenal surface of rat lung microvascular endothelium. Lungs were perfused in situ for 4 h at 37 degrees C with a solution of 100 mM formaldehyde, 2 mM dithiothreitol in phosphate-buffered saline to induce endothelial cell vesiculation. Radioiodinated rat lung endothelial cell membrane vesicles bound lung-metastatic tumor cells (B16F10, R323OAC-MET) in significantly higher numbers than their low or nonmetastatic counterparts (B16F0, R323OAC-LR). In contrast, leg endothelial membrane vesicle showed no binding preference for either cell line. Neuraminidase treatment of vesicles abolished specificity of adhesion of lung-derived vesicles to lung metastatic tumor cells. These results demonstrate that in situ perfusion is an appropriate technique to obtain pure endothelial cell membrane vesicles containing functionally active adhesion molecules. The preferential binding of lung-derived endothelial cell membrane vesicles by lung metastatic tumor cells is evidence of the importance of endothelial cell adhesion molecules in the formation of metastases.

The protective effect of dexmedetomidine in a rat ex vivo lung model of ischemia-reperfusion injury.

PubMed

Zhou, Yan; Zhou, Xinqiao; Zhou, Wenjuan; Pang, Qingfeng; Wang, Zhiping

2018-01-01

To investigate the effect of dexmedetomidine (Dex) in a rat ex vivo lung model of ischemia-reperfusion injury. An IL-2 ex vivo lung perfusion system was used to establish a rat ex vivo lung model of ischemia-reperfusion injury. Drugs were added to the perfusion solution for reperfusion. Lung injury was assessed by histopathological changes, airway pressure (Res), lung compliance (Compl), perfusion flow (Flow), pulmonary venous oxygen partial pressure (PaO2), and lung wet/dry (W/D) weight ratio. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), 78 kDa glucose-regulated protein (GRP78) and CCAAT/enhancer-binding protein homologous protein (CHOP) were measured, respectively. The introduction of Dex attenuated the post-ischemia-reperfusion lung damage and MDA level, improved lung histology, W/D ratio, lung injury scores and SOD activity. Decreased mRNA and protein levels of GRP78 and CHOP compared with the IR group were observed after Dex treatment. The effect of Dex was dosage-dependence and a high dose of Dex (10 nM) was shown to confer the strongest protective effect against lung damage (P<0.05). Yohimbine, an α2 receptor antagonist, significantly reversed the protective effect of Dex in lung tissues (P<0.05). Dex reduced ischemia-reperfusion injury in rat ex vivo lungs.

Minimally invasive monitoring of skeletal muscle hypermetabolism induced by the phosphodiesterase-III-inhibitor milrinone and sodium fluoride.

PubMed

Schuster, Frank; Johannsen, Stephan; Roewer, Norbert; Anetseder, Martin

2013-04-01

We hypothesized that the phosphodiesterase-III-inhibitor milrinone and the non-specific G-protein activator sodium fluoride increase the skeletal muscular lactate levels as a sign of a hypermetabolic response. With approval of the local animal care committee Sprague-Dawley rats were killed and artificially perfused either with Ringer's solution or sodium fluoride 110 mM, while milrinone 1.32 mM or Ringer's solution at 1 μl/min was applied via microdialysis probes in both hind limbs. Lactate was measured spectrophotometrically in the dialysate. Baseline lactate levels before drug application did not differ between hind limbs. Local infusion of milrinone via microdialysis did not significantly increase intramuscular lactate concentrations compared with the Ringer control group. Muscular perfusion with sodium fluoride resulted in a significant increase of lactate and was potentiated by combination with local milrinone. Phosphodiesterase-III-inhibition alone does not significantly influence the lactate levels in skeletal muscle of sacrificed rats. Sodium fluoride infusion leads to an intramuscular lactate increase, which was further potentiated by local inhibition of phosphodiesterase-III. The fluoride-mediated hypermetabolic response following sodium fluoride could be a possible explanation for the observed myotoxic adverse effects in individuals treated by fluoride-containing agents. © 2012 The Authors. JPP © 2012. Royal Pharmaceutical Society.

CAD system for automatic analysis of CT perfusion maps

NASA Astrophysics Data System (ADS)

Hachaj, T.; Ogiela, M. R.

2011-03-01

In this article, authors present novel algorithms developed for the computer-assisted diagnosis (CAD) system for analysis of dynamic brain perfusion, computer tomography (CT) maps, cerebral blood flow (CBF), and cerebral blood volume (CBV). Those methods perform both quantitative analysis [detection and measurement and description with brain anatomy atlas (AA) of potential asymmetries/lesions] and qualitative analysis (semantic interpretation of visualized symptoms). The semantic interpretation (decision about type of lesion: ischemic/hemorrhagic, is the brain tissue at risk of infraction or not) of visualized symptoms is done by, so-called, cognitive inference processes allowing for reasoning on character of pathological regions based on specialist image knowledge. The whole system is implemented in.NET platform (C# programming language) and can be used on any standard PC computer with.NET framework installed.

Glioblastoma: Vascular Habitats Detected at Preoperative Dynamic Susceptibility-weighted Contrast-enhanced Perfusion MR Imaging Predict Survival.

PubMed

Juan-Albarracín, Javier; Fuster-Garcia, Elies; Pérez-Girbés, Alexandre; Aparici-Robles, Fernando; Alberich-Bayarri, Ángel; Revert-Ventura, Antonio; Martí-Bonmatí, Luis; García-Gómez, Juan M

2018-06-01

Purpose To determine if preoperative vascular heterogeneity of glioblastoma is predictive of overall survival of patients undergoing standard-of-care treatment by using an unsupervised multiparametric perfusion-based habitat-discovery algorithm. Materials and Methods Preoperative magnetic resonance (MR) imaging including dynamic susceptibility-weighted contrast material-enhanced perfusion studies in 50 consecutive patients with glioblastoma were retrieved. Perfusion parameters of glioblastoma were analyzed and used to automatically draw four reproducible habitats that describe the tumor vascular heterogeneity: high-angiogenic and low-angiogenic regions of the enhancing tumor, potentially tumor-infiltrated peripheral edema, and vasogenic edema. Kaplan-Meier and Cox proportional hazard analyses were conducted to assess the prognostic potential of the hemodynamic tissue signature to predict patient survival. Results Cox regression analysis yielded a significant correlation between patients' survival and maximum relative cerebral blood volume (rCBV max ) and maximum relative cerebral blood flow (rCBF max ) in high-angiogenic and low-angiogenic habitats (P < .01, false discovery rate-corrected P < .05). Moreover, rCBF max in the potentially tumor-infiltrated peripheral edema habitat was also significantly correlated (P < .05, false discovery rate-corrected P < .05). Kaplan-Meier analysis demonstrated significant differences between the observed survival of populations divided according to the median of the rCBV max or rCBF max at the high-angiogenic and low-angiogenic habitats (log-rank test P < .05, false discovery rate-corrected P < .05), with an average survival increase of 230 days. Conclusion Preoperative perfusion heterogeneity contains relevant information about overall survival in patients who undergo standard-of-care treatment. The hemodynamic tissue signature method automatically describes this heterogeneity, providing a set of vascular habitats with high prognostic capabilities. © RSNA, 2018.

Prediction of Therapeutic Effect of Chemotherapy for NSCLC Using Dual-Input Perfusion CT Analysis: Comparison among Bevacizumab Treatment, Two-Agent Platinum-based Therapy without Bevacizumab, and Other Non-Bevacizumab Treatment Groups.

PubMed

Yabuuchi, Hidetake; Kawanami, Satoshi; Iwama, Eiji; Okamoto, Isamu; Kamitani, Takeshi; Sagiyama, Koji; Yamasaki, Yuzo; Honda, Hiroshi

2018-02-01

Purpose To determine whether dual-input perfusion computed tomography (CT) can predict therapeutic response and prognosis in patients who underwent chemotherapy for non-small cell lung cancer (NSCLC). Materials and Methods The institutional review board approved this study and informed consent was obtained. Sixty-six patients with stage III or IV NSCLC (42 men, 24 women; mean age, 63.4 years) who underwent chemotherapy were enrolled. Patients were separated into three groups: those who received chemotherapy with bevacizumab (BV) (n = 20), those who received two-agent platinum-based therapy without BV (n = 25), and those who received other non-BV treatment (n = 21). Before treatment, pulmonary artery perfusion (PAP) and bronchial artery perfusion (BAP) of the tumors were calculated. Predictors of tumor reduction after two courses of chemotherapy and prognosis were identified by using univariate and multivariate analyses. Covariates included were age, sex, patient's performance status, baseline maximum diameter of the tumor, clinical stage, pretreatment PAP, and pretreatment BAP. For multivariate analyses, multiple linear regression analysis for tumor reduction rate and Cox proportional hazards model for prognosis were performed, respectively. Results Pretreatment BAP was independently correlated with tumor reduction rate after two courses of chemotherapy in the BV treatment group (P = .006). Pretreatment BAP was significantly associated with a highly cumulative risk of death (P = .006) and disease progression after chemotherapy (P = .015) in the BV treatment group. Pretreatment PAP and clinical parameters were not significant predictors of therapeutic effect or prognosis in three treatment groups. Conclusion Pretreatment BAP derived from dual-input perfusion CT seems to be a promising tool to help predict responses to chemotherapy with BV in patients with NSCLC. © RSNA, 2017.

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

PubMed

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

2011-01-01

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

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.

Quantitative fluorescence angiography for neurosurgical interventions.

PubMed

Weichelt, Claudia; Duscha, Philipp; Steinmeier, Ralf; Meyer, Tobias; Kuß, Julia; Cimalla, Peter; Kirsch, Matthias; Sobottka, Stephan B; Koch, Edmund; Schackert, Gabriele; Morgenstern, Ute

2013-06-01

Present methods for quantitative measurement of cerebral perfusion during neurosurgical operations require additional technology for measurement, data acquisition, and processing. This study used conventional fluorescence video angiography--as an established method to visualize blood flow in brain vessels--enhanced by a quantifying perfusion software tool. For these purposes, the fluorescence dye indocyanine green is given intravenously, and after activation by a near-infrared light source the fluorescence signal is recorded. Video data are analyzed by software algorithms to allow quantification of the blood flow. Additionally, perfusion is measured intraoperatively by a reference system. Furthermore, comparing reference measurements using a flow phantom were performed to verify the quantitative blood flow results of the software and to validate the software algorithm. Analysis of intraoperative video data provides characteristic biological parameters. These parameters were implemented in the special flow phantom for experimental validation of the developed software algorithms. Furthermore, various factors that influence the determination of perfusion parameters were analyzed by means of mathematical simulation. Comparing patient measurement, phantom experiment, and computer simulation under certain conditions (variable frame rate, vessel diameter, etc.), the results of the software algorithms are within the range of parameter accuracy of the reference methods. Therefore, the software algorithm for calculating cortical perfusion parameters from video data presents a helpful intraoperative tool without complex additional measurement technology.

Multiattribute selection of acute stroke imaging software platform for Extending the Time for Thrombolysis in Emergency Neurological Deficits (EXTEND) clinical trial.

PubMed

Churilov, Leonid; Liu, Daniel; Ma, Henry; Christensen, Soren; Nagakane, Yoshinari; Campbell, Bruce; Parsons, Mark W; Levi, Christopher R; Davis, Stephen M; Donnan, Geoffrey A

2013-04-01

The appropriateness of a software platform for rapid MRI assessment of the amount of salvageable brain tissue after stroke is critical for both the validity of the Extending the Time for Thrombolysis in Emergency Neurological Deficits (EXTEND) Clinical Trial of stroke thrombolysis beyond 4.5 hours and for stroke patient care outcomes. The objective of this research is to develop and implement a methodology for selecting the acute stroke imaging software platform most appropriate for the setting of a multi-centre clinical trial. A multi-disciplinary decision making panel formulated the set of preferentially independent evaluation attributes. Alternative Multi-Attribute Value Measurement methods were used to identify the best imaging software platform followed by sensitivity analysis to ensure the validity and robustness of the proposed solution. Four alternative imaging software platforms were identified. RApid processing of PerfusIon and Diffusion (RAPID) software was selected as the most appropriate for the needs of the EXTEND trial. A theoretically grounded generic multi-attribute selection methodology for imaging software was developed and implemented. The developed methodology assured both a high quality decision outcome and a rational and transparent decision process. This development contributes to stroke literature in the area of comprehensive evaluation of MRI clinical software. At the time of evaluation, RAPID software presented the most appropriate imaging software platform for use in the EXTEND clinical trial. The proposed multi-attribute imaging software evaluation methodology is based on sound theoretical foundations of multiple criteria decision analysis and can be successfully used for choosing the most appropriate imaging software while ensuring both robust decision process and outcomes. © 2012 The Authors. International Journal of Stroke © 2012 World Stroke Organization.

Effect of hypothermic pulmonary artery flushing on capillary filtration coefficient.

PubMed

Andrade, R S; Wangensteen, O D; Jo, J K; Tsai, M Y; Bolman, R M

2000-07-27

We previously demonstrated that surfactant dilution and inhibition occur immediately after pulmonary artery flushing with hypothermic modified Euro-Collins solution. Consequently, we speculated that increased capillary permeability contributed to these surfactant changes. To test this hypothesis, we evaluated the effects of hypothermic pulmonary artery flushing on the pulmonary capillary filtration coefficient (Kfc), and additionally performed a biochemical analysis of surfactant. We used a murine isolated, perfused lung model to measure the pulmonary capillary filtration coefficient and hemodynamic parameters, to determine the wet to dry weight ratio, and to evaluate surfactant by biochemical analysis of lung lavage fluid. We defined three study groups. In group I (controls), we harvested lungs without hypothermic pulmonary artery flushing, and measured Kfc immediately. In group II (in situ flush), we harvested lungs after hypothermic pulmonary artery flushing with modified Euro-Collins solution, and then measured Kfc. Experiments in groups I and II were designed to evaluate persistent changes in Kfc after pulmonary artery flushing. In group III (ex vivo flush), we flushed lungs ex vivo to evaluate transient changes in Kfc during hypothermic pulmonary artery flushing. Groups I and II did not differ significantly in capillary filtration coefficient and hemodynamics. Group II showed significant alterations on biochemical surfactant analysis and a significant increase in wet-to-dry weight ratio, when compared with group I. In group III, we observed a significant transient increase in capillary filtration coefficient during pulmonary artery flushing. Hypothermic pulmonary artery flushing transiently increases the capillary filtration coefficient, leads to an increase in the wet to dry weight ratio, and induces biochemical surfactant changes. These findings could be explained by the effects of hypothermic modified Euro-Collins solution on pulmonary capillary permeability.

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

PubMed Central

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

2004-01-01

Background Investigation of bioheat transfer problems requires the evaluation of temporal and spatial distributions of temperature. This class of problems has been traditionally addressed using the Pennes bioheat equation. Transport of heat by conduction, and by temperature-dependent, spatially heterogeneous blood perfusion is modeled here using a transport lattice approach. Methods We represent heat transport processes by using a lattice that represents the Pennes bioheat equation in perfused tissues, and diffusion in nonperfused regions. The three layer skin model has a nonperfused viable epidermis, and deeper regions of dermis and subcutaneous tissue with perfusion that is constant or temperature-dependent. Two cases are considered: (1) surface contact heating and (2) spatially distributed heating. The model is relevant to the prediction of the transient and steady state temperature rise for different methods of power deposition within the skin. Accumulated thermal damage is estimated by using an Arrhenius type rate equation at locations where viable tissue temperature exceeds 42°C. Prediction of spatial temperature distributions is also illustrated with a two-dimensional model of skin created from a histological image. Results The transport lattice approach was validated by comparison with an analytical solution for a slab with homogeneous thermal properties and spatially distributed uniform sink held at constant temperatures at the ends. For typical transcutaneous blood gas sensing conditions the estimated damage is small, even with prolonged skin contact to a 45°C surface. Spatial heterogeneity in skin thermal properties leads to a non-uniform temperature distribution during a 10 GHz electromagnetic field exposure. A realistic two-dimensional model of the skin shows that tissue heterogeneity does not lead to a significant local temperature increase when heated by a hot wire tip. Conclusions The heat transport system model of the skin was solved by exploiting the mathematical analogy between local thermal models and local electrical (charge transport) models, thereby allowing robust, circuit simulation software to obtain solutions to Kirchhoff's laws for the system model. Transport lattices allow systematic introduction of realistic geometry and spatially heterogeneous heat transport mechanisms. Local representations for both simple, passive functions and more complex local models can be easily and intuitively included into the system model of a tissue. PMID:15548324

Brain SPECT scans in students with specific learning disability: Preliminary results.

PubMed

Karande, S; Deshmukh, N; Rangarajan, V; Agrawal, A; Sholapurwala, R

2018-06-08

Brain single-photon emission computed tomography (SPECT) assesses brain function through measurement of regional cerebral blood flow. This study was conducted to assess whether students with newly diagnosed specific learning disability (SpLD) show any abnormalities in cerebral cortex perfusion. Cross-sectional single-arm pilot study in two tertiary care hospitals. Nine students with SpLD were enrolled. Brain SPECT scan was done twice in each student. For the first or "baseline" scan, the student was first made to sit with eyes open in a quiet, dimly lit room for a period of 30-40 min and then injected intravenously with 20 mCi of 99mTc-ECD. An hour later, "baseline scan" was conducted. After a minimum gap of 4 days, a second or "test scan" was conducted, wherein the student performed an age-appropriate curriculum-based test for a period of 30-40 min to activate the areas in central nervous system related to learning before being injected with 20 mCi of 99mTc-ECD. Cerebral cortex perfusion at rest and after activation in each student was compared qualitatively by visual analysis and quantitatively using NeuroGam TM software. Visual analysis showed reduction in regional blood flow in temporoparietal areas in both "baseline" and "test" scans. However, when normalization was attempted and comparison done by Talairach analysis using NeuroGam software, no statistically significant change in regional perfusion in temporoparietal areas was appreciated. Brain SPECT scan may serve as a robust tool to identify changes in regional brain perfusion in students with SpLD.

Brain perfusion alterations in depressed patients with Parkinson's disease.

PubMed

Kim, Young-Do; Jeong, Hyeonseok S; Song, In-Uk; Chung, Yong-An; Namgung, Eun; Kim, Yong-Duk

2016-12-01

Although Parkinson's disease (PD) is frequently accompanied by depression, brain perfusion deficits in PD with depression remain unclear. This study aimed to assess alterations in regional cerebral blood flow (rCBF) in depressed PD patients using 99m Tc hexamethyl-propylene-amine-oxime single-photon emission computed tomography (SPECT). Among 78 patients with PD, 35 patients were classified into the depressed PD group, while the rest (43 patients) was assigned to the nondepressed PD group based on the scores of the Geriatric Depressive Scale (GDS). All participants underwent brain SPECT imaging. The voxel-wise whole-brain analysis and region-of-interest (ROI) analysis of the limbic areas were conducted to compare rCBF between the depressed and nondepressed PD groups. The depressed PD patients demonstrated higher GDS scores than nondepressed patients, whereas between-group differences in the PD severity and cognitive function were not significant. Perfusion in the left cuneus was increased, while that in the right superior temporal gyrus and right medial orbitofrontal cortex was reduced in the depressed PD patients as compared with nondepressed PD patients. In addition, the ROI analysis demonstrated rCBF decreases in the amygdala, anterior cingulate cortex, hippocampus, and parahippocampal gyrus in the depressed PD group. A positive correlation was found between the GDS scores and rCBF in the left cuneus cluster in the depressed PD patients. This study identified the regional pattern of brain perfusion that distinguished depressed from nondepressed PD patients. Hyperperfusion in the occipital areas and hypoperfusion in the fronto-temporo-limbic regions may be potential imaging biomarkers for depression in PD.

Toward a practical template-based approach to semiquantitative SPECT myocardial perfusion imaging.

PubMed

Hughes, Tyler; Celler, Anna

2012-03-01

Our template-based quantitative perfusion single photon emission computed tomography (SPECT) method (T-QPS) performs semiquantitative analysis for myocardial perfusion imaging (MPI) without the use of normal databases. However, in its current form, T-QPS requires extensive calculations, which limits its clinical application. In the interest of clinical feasibility, the authors examine the trade-off between accuracy and processing time as the method is simplified. The T-QPS method uses the reconstructed SPECT image of the patient to create a 3D digital template of his∕her healthy heart. This template is then projected, reconstructed, and sampled into the bulls-eye map domain. A ratio of the patient and template images produces a final corrected image in which a threshold is applied to identify perfusion defects. In principle, the template should be constructed with the heart and all extracardiac activity, and the projection step should include primary and scatter components; however, this leads to lengthy calculations. In an attempt to shorten the processing time, the authors analyzed the performance of four template (T) generation methods: T(P-HRT), T(PS-HRT), T(P-HRTBKG), and T(PS-HRTBKG), where P and S represent primary and scattered photons included in the projection step, respectively; and HRT and HRTBKG represent template constructed with the heart only and the heart with background activity, respectively. Forty-eight thorax phantoms and 21 randomly selected patient studies were analyzed using each approach. All studies used GE's Infinia Hawkeye SPECT∕CT system and followed a standard cardiac acquisition protocol. Approximate processing times for the T(P-HRT), T(PS-HRT), T(P-HRTBKG), and T(PS-HRTBKG) methods were less than a minute, 2-3 h, less than a minute and 3-4 h, respectively. In both the simulation and patient studies, a significant reduction in the quality of perfusion defect definition was exhibited by the T(P-HRT) method relative to the other three methods. The optimal method with respect to perfusion defect definition and processing time was T(P-HRTBKG) with a sensitivity, specificity, and accuracy in spatially defining the perfusion defects (simulation study) of 80%, 84%, and 83%, respectively. The T-QPS method using T(P-HRTBKG) leads to accurate and fast semiquantitative analysis of SPECT MPI, without the use of normal databases.

Electrolyte and protein secretion by the perfused rabbit mandibular gland stimulated with acetylcholine or catecholamines

PubMed Central

Case, R. M.; Conigrave, A. D.; Novak, I.; Young, J. A.

1980-01-01

1. A method is described for the isolation and vascular perfusion in vitro of the mandibular gland of the rabbit. The perfusate is a physiological salt solution containing glucose as the only metabolic substrate. 2. During perfusion with solutions containing acetylcholine, the gland secretes vigorously at a rate and in a manner similar to that seen in vivo. Although the gland becomes oedematous during perfusion, the extent of this oedema appears to have no influence on secretory ability: the perfused glands were capable of functioning for at least 4 h, and often for more than 6 h. 3. Acetylcholine evoked a small secretory response at a concentration of 8 × 10-9 mol l-1 and a maximum response at 8 × 10-7 mol l-1. Eserine (2 × 10-5 mol l-1) evoked secretory responses comparable to those evoked by acetylcholine in a concentration of 8 × 10-9 mol l-1. Secretion, whether unstimulated or evoked by acetylcholine or eserine, could be blocked completely by atropine. 4. During prolonged stimulation with acetylcholine, the fluid secretory response declined rapidly over a period of about 15 min from an initial high value to a much lower plateau value. After 3 or more hours of stimulation, the secretory response began once more to decline, this time towards zero. If, before the second period of decline begins, stimulation is interrupted for about 30 min, the gland recovers its initial responsiveness to further stimulation with acetylcholine. 5. The Na, K, Cl and HCO3 concentrations and the osmolality of acetylcholine evoked saliva exhibited flow-dependency similar to that seen in vivo. The concentrations of Na and Cl, but not K and HCO3, increased by about 25 mmol l-1 during periods of prolonged stimulation with acetylcholine even though the salivary secretory rate was constant. The concentrations of K and HCO3, but not Na and Cl, increased progressively as the concentration of infused acetylcholine was increased. 6. Salivary protein secretion increased with increasing concentrations of acetylcholine to a greater extent than did fluid secretion. During continuous stimulation, the rate of protein secretion fell off much faster than the rate of fluid secretion. 7. The β-adrenergic agonist isoproterenol evoked a fluid secretory response only equal to about 5% of that evoked by acetylcholine, but still the response declined during continued stimulation. The electrolyte composition of isoproterenol-evoked saliva was vastly different from that evoked by acetylcholine, being particularly rich in K and HCO3. The isoproterenol-evoked saliva was also extremely rich in protein so that the total protein secretion evoked by isoproterenol was much greater than that evoked by acetylcholine. 8. The α-adrenergic agonist phenylephrine was without stimulatory effect on salivary fluid secretion and caused a reduction in the secretory response to acetylcholine. The drug had little or no effect on the electrolyte content of acetylcholine-evoked saliva and appeared to reduce its protein content. PMID:7381794

Palatal mucosa necrosis because of accidental sodium hypochlorite injection instead of anaesthetic solution.

PubMed

Gursoy, U K; Bostanci, V; Kosger, H H

2006-02-01

A case is reported in which sodium hypochlorite (NaOCl) was inadvertently injected into the palatal mucosa instead of local anaesthetic solution. An adult male was referred to the University clinic 15 days after an inadvertent NaOCl injection into the palatal mucosa. Soft tissue necrosis was evident, without obvious bony involvement. Tissues healed without scarring within 30 days. No surgical intervention was required. NaOCl is highly irritant when extruded into vital tissues.--Dentists should be careful to avoid the misuse of NaOCl, and should check the nature of any agent before injecting it into patients.--NaOCl should not be dispensed in a way that could allow it to be mistaken for local anaesthetic solutions.--The well-perfused tissues of the oral cavity have considerable healing ability.

Using Dynamic Contrast Enhanced MRI to Quantitatively Characterize Maternal Vascular Organization in the Primate Placenta

PubMed Central

Frias, A.E.; Schabel, M.C.; Roberts, V.H.J.; Tudorica, A.; Grigsby, P.L.; Oh, K.Y.; Kroenke, C. D.

2015-01-01

Purpose The maternal microvasculature of the primate placenta is organized into 10-20 perfusion domains that are functionally optimized to facilitate nutrient exchange to support fetal growth. This study describes a dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) method for identifying vascular domains, and quantifying maternal blood flow in them. Methods A rhesus macaque on the 133rd day of pregnancy (G133, term=165 days) underwent Doppler ultrasound (US) procedures, DCE-MRI, and Cesarean-section delivery. Serial T1-weighted images acquired throughout intravenous injection of a contrast reagent (CR) bolus were analyzed to obtain CR arrival time maps of the placenta. Results Watershed segmentation of the arrival time map identified 16 perfusion domains. The number and location of these domains corresponded to anatomical cotyledonary units observed following delivery. Analysis of the CR wave front through each perfusion domain enabled determination of volumetric flow, which ranged from 9.03 to 44.9 mL/sec (25.2 ± 10.3 mL/sec). These estimates are supported by Doppler US results. Conclusions The DCE-MRI analysis described here provides quantitative estimates of the number of maternal perfusion domains in a primate placenta, and estimates flow within each domain. Anticipated extensions of this technique are to the study placental function in nonhuman primate models of obstetric complications. PMID:24753177

Comparison of conventional and cadmium-zinc-telluride single-photon emission computed tomography for analysis of thallium-201 myocardial perfusion imaging: an exploratory study in normal databases for different ethnicities.

PubMed

Ishihara, Masaru; Onoguchi, Masahisa; Taniguchi, Yasuyo; Shibutani, Takayuki

2017-12-01

The aim of this study was to clarify the differences in thallium-201-chloride (thallium-201) myocardial perfusion imaging (MPI) scans evaluated by conventional anger-type single-photon emission computed tomography (conventional SPECT) versus cadmium-zinc-telluride SPECT (CZT SPECT) imaging in normal databases for different ethnic groups. MPI scans from 81 consecutive Japanese patients were examined using conventional SPECT and CZT SPECT and analyzed with the pre-installed quantitative perfusion SPECT (QPS) software. We compared the summed stress score (SSS), summed rest score (SRS), and summed difference score (SDS) for the two SPECT devices. For a normal MPI reference, we usually use Japanese databases for MPI created by the Japanese Society of Nuclear Medicine, which can be used with conventional SPECT but not with CZT SPECT. In this study, we used new Japanese normal databases constructed in our institution to compare conventional and CZT SPECT. Compared with conventional SPECT, CZT SPECT showed lower SSS (p < 0.001), SRS (p = 0.001), and SDS (p = 0.189) using the pre-installed SPECT database. In contrast, CZT SPECT showed no significant difference from conventional SPECT in QPS analysis using the normal databases from our institution. Myocardial perfusion analyses by CZT SPECT should be evaluated using normal databases based on the ethnic group being evaluated.

Validation of 18F-fluoro-4-thia-palmitate as a PET probe for myocardial fatty acid oxidation: effects of hypoxia and composition of exogenous fatty acids.

PubMed

DeGrado, Timothy R; Kitapci, Mehmet T; Wang, Shuyan; Ying, Jun; Lopaschuk, Gary D

2006-01-01

Fatty acid oxidation (FAO) is the predominant energy-producing pathway in the healthy heart. Abnormalities in FAO are associated with many ischemic and nonischemic disease states. The aim of the present study was to further validate 16-[(18)F]-fluoro-4-thia-palmitate ((18)F-FTP) as a metabolically trapped FAO probe in the isolated perfused rat heart model by examining both the effects of hypoxia and the effects of changes in exogenous fatty acid availability. Hearts were excised from Sprague-Dawley rats and perfused in the Langendorff mode with Krebs-Henseleit solution under the following conditions: palmitate at 0.4 mmol/L with 95% oxygen, palmitate at 0.4 mmol/L with 35% oxygen, palmitate at 0.2 mmol/L plus oleate at 0.2 mmol/L with 95% oxygen, and palmitate at 0.2 mmol/L plus oleate at 0.2 mmol/L with 35% oxygen. Hearts were paced at 270 beats per minute, and the rate of left ventricular pressure change (LV dP/dt) was monitored. (18)F-FTP in the perfusion medium was administered for 20 min, and this step was followed by a 20-min washout period without tracer in the perfusion medium. (18)F kinetics in the whole heart were monitored externally, and the time-activity curves were analyzed to determine the fractional trapping rate for (18)F-FTP (FTR(FTP)). A "lumped constant" (LC) was defined as the ratio of FTR(FTP) to the fractional rate of oxidation of fatty acid in the perfusion medium. The kinetic data for (18)F-FTP demonstrated metabolic trapping of (18)F radioactivity that was insensitive to changes in the mixture of fatty acids in the perfusion medium but that was sensitive to the inhibition of mitochondrial FAO by hypoxia. LV dP/dt was reduced 47%-67% in hypoxic hearts relative to hearts with normal oxygenation (controls). FAO rates for palmitate and oleate were similar in group 3 (palmitate alone) and group 4 (palmitate and oleate). FAO was decreased 70%-76% with hypoxia, whereas FTR(FTP) was reduced 86%-88%, demonstrating hypersensitivity of a change in (18)F-FTP retention to FAO inhibition by oxygen deprivation. The (18)F-FTP LC was approximately 2 in myocardium with normal oxygenation and fell to 1.0-1.2 in hypoxic myocardium. The results confirm (18)F-FTP to be a metabolically trapped palmitate analog that is capable of indicating rates of myocardial oxidation of exogenous long-chain fatty acids. The heterogeneous nature of fatty acids in plasma does not alter the quantitative analysis of (18)F-FTP kinetics. However, the decreased LC value in hypoxic myocardium suggests the need to develop an understanding of the relationship of (18)F-FTP processing to natural fatty acids at key limiting transport and metabolism processes, analogous to previous studies examining the LC values for radiolabeled deoxyglucose tracers used to estimate the glucose metabolic rate.

Magnetic resonance perfusion for differentiating low-grade from high-grade gliomas at first presentation.

PubMed

Abrigo, Jill M; Fountain, Daniel M; Provenzale, James M; Law, Eric K; Kwong, Joey Sw; Hart, Michael G; Tam, Wilson Wai San

2018-01-22

Gliomas are the most common primary brain tumour. They are graded using the WHO classification system, with Grade II-IV astrocytomas, oligodendrogliomas and oligoastrocytomas. Low-grade gliomas (LGGs) are WHO Grade II infiltrative brain tumours that typically appear solid and non-enhancing on magnetic resonance imaging (MRI) scans. People with LGG often have little or no neurologic deficit, so may opt for a watch-and-wait-approach over surgical resection, radiotherapy or both, as surgery can result in early neurologic disability. Occasionally, high-grade gliomas (HGGs, WHO Grade III and IV) may have the same MRI appearance as LGGs. Taking a watch-and-wait approach could be detrimental for the patient if the tumour progresses quickly. Advanced imaging techniques are increasingly used in clinical practice to predict the grade of the tumour and to aid clinical decision of when to intervene surgically. One such advanced imaging technique is magnetic resonance (MR) perfusion, which detects abnormal haemodynamic changes related to increased angiogenesis and vascular permeability, or "leakiness" that occur with aggressive tumour histology. These are reflected by changes in cerebral blood volume (CBV) expressed as rCBV (ratio of tumoural CBV to normal appearing white matter CBV) and permeability, measured by K trans . To determine the diagnostic test accuracy of MR perfusion for identifying patients with primary solid and non-enhancing LGGs (WHO Grade II) at first presentation in children and adults. In performing the quantitative analysis for this review, patients with LGGs were considered disease positive while patients with HGGs were considered disease negative.To determine what clinical features and methodological features affect the accuracy of MR perfusion. Our search strategy used two concepts: (1) glioma and the various histologies of interest, and (2) MR perfusion. We used structured search strategies appropriate for each database searched, which included: MEDLINE (Ovid SP), Embase (Ovid SP), and Web of Science Core Collection (Science Citation Index Expanded and Conference Proceedings Citation Index). The most recent search for this review was run on 9 November 2016.We also identified 'grey literature' from online records of conference proceedings from the American College of Radiology, European Society of Radiology, American Society of Neuroradiology and European Society of Neuroradiology in the last 20 years. The titles and abstracts from the search results were screened to obtain full-text articles for inclusion or exclusion. We contacted authors to clarify or obtain missing/unpublished data.We included cross-sectional studies that performed dynamic susceptibility (DSC) or dynamic contrast-enhanced (DCE) MR perfusion or both of untreated LGGs and HGGs, and where rCBV and/or K trans values were reported. We selected participants with solid and non-enhancing gliomas who underwent MR perfusion within two months prior to histological confirmation. We excluded studies on participants who received radiation or chemotherapy before MR perfusion, or those without histologic confirmation. Two review authors extracted information on study characteristics and data, and assessed the methodological quality using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. We present a summary of the study characteristics and QUADAS-2 results, and rate studies as good quality when they have low risk of bias in the domains of reference standard of tissue diagnosis and flow and timing between MR perfusion and tissue diagnosis.In the quantitative analysis, LGGs were considered disease positive, while HGGs were disease negative. The sensitivity refers to the proportion of LGGs detected by MR perfusion, and specificity as the proportion of detected HGGs. We constructed two-by-two tables with true positives and false negatives as the number of correctly and incorrectly diagnosed LGG, respectively, while true negatives and false positives are the number of correctly and incorrectly diagnosed HGG, respectively.Meta-analysis was performed on studies with two-by-two tables, with further sensitivity analysis using good quality studies. Limited data precluded regression analysis to explore heterogeneity but subgroup analysis was performed on tumour histology groups. Seven studies with small sample sizes (4 to 48) met our inclusion criteria. These were mostly conducted in university hospitals and mostly recruited adult patients. All studies performed DSC MR perfusion and described heterogeneous acquisition and post-processing methods. Only one study performed DCE MR perfusion, precluding quantitative analysis.Using patient-level data allowed selection of individual participants relevant to the review, with generally low risks of bias for the participant selection, reference standard and flow and timing domains. Most studies did not use a pre-specified threshold, which was considered a significant source of bias, however this did not affect quantitative analysis as we adopted a common rCBV threshold of 1.75 for the review. Concerns regarding applicability were low.From published and unpublished data, 115 participants were selected and included in the meta-analysis. Average rCBV (range) of 83 LGGs and 32 HGGs were 1.29 (0.01 to 5.10) and 1.89 (0.30 to 6.51), respectively. Using the widely accepted rCBV threshold of <1.75 to differentiate LGG from HGG, the summary sensitivity/specificity estimates were 0.83 (95% CI 0.66 to 0.93)/0.48 (95% CI 0.09 to 0.90). Sensitivity analysis using five good quality studies yielded sensitivity/specificity of 0.80 (95% CI 0.61 to 0.91)/0.67 (95% CI 0.07 to 0.98). Subgroup analysis for tumour histology showed sensitivity/specificity of 0.92 (95% CI 0.55 to 0.99)/0.42 (95% CI 0.02 to 0.95) in astrocytomas (6 studies, 55 participants) and 0.77 (95% CI 0.46 to 0.93)/0.53 (95% CI 0.14 to 0.88) in oligodendrogliomas+oligoastrocytomas (6 studies, 56 participants). Data were too sparse to investigate any differences across subgroups. The limited available evidence precludes reliable estimation of the performance of DSC MR perfusion-derived rCBV for the identification of grade in untreated solid and non-enhancing LGG from that of HGG. Pooled data yielded a wide range of estimates for both sensitivity (range 66% to 93% for detection of LGGs) and specificity (range 9% to 90% for detection of HGGs). Other clinical and methodological features affecting accuracy of the technique could not be determined from the limited data. A larger sample size of both LGG and HGG, preferably using a standardised scanning approach and with an updated reference standard incorporating molecular profiles, is required for a definite conclusion.

CT perfusion imaging of the stomach: a quantitative analysis according to different degrees of adenocarcinoma cell differentiation.

PubMed

Zongqiong, Sun; Xiaohong, Li; Wei, Cai; Jiangfeng, Zhou; Yuxi, Ge; Zhihui, Xie; Linfang, Jin; Yong, Pu; Gen, Yan

2016-01-01

To evaluate clinical usefulness of computed tomography perfusion imaging (CTPI) in gastric cancer. Twenty subjects without gastric diseases (control group) and fifty patients with gastric cancer were studied prospectively using CTPI examinations. Four perfusion parameter values, i.e., blood flow (BF), blood volume (BV), mean transit time, and permeability surface (PS), were calculated. The gastric cancer group was divided into three groups: well differentiated, moderately differentiated, and poorly differentiated gastric adenocarcinoma. Comparing the three groups, differences between the well-differentiated group and the moderately differentiated group or the poorly differentiated group were all statistically significant for BF, BV, and PS. The BF, BV, and PS values could serve as indicators of the degree of malignancy of gastric cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Beware Cold Agglutinins in Organ Donors! Ex Vivo Lung Perfusion From an Uncontrolled Donation After Circulatory-Determination-of-Death Donor With a Cold Agglutinin: A Case Report.

PubMed

Venkataraman, A; Blackwell, J W; Funkhouser, W K; Birchard, K R; Beamer, S E; Simmons, W T; Randell, S H; Egan, T M

2017-09-01

We began to recover lungs from uncontrolled donation after circulatory determination of death to assess for transplant suitability by means of ex vivo lung perfusion (EVLP) and computerized tomographic (CT) scan. Our first case had a cold agglutinin with an interesting outcome. A 60-year-old man collapsed at home and was pronounced dead by Emergency Medical Services personnel. Next-of-kin consented to lung retrieval, and the decedent was ventilated and transported. Lungs were flushed with cold Perfadex, removed, and stored cold. The lungs did not flush well. Medical history revealed a recent hemolytic anemia and a known cold agglutinin. Warm nonventilated ischemia time was 51 minutes. O 2 -ventilated ischemia time was 141 minutes. Total cold ischemia time was 6.5 hours. At cannulation for EVLP, established clots were retrieved from both pulmonary arteries. At initiation of EVLP with Steen solution, tiny red aggregates were observed initially. With warming, the aggregates disappeared and the perfusate became red. After 1 hour, EVLP was stopped because of florid pulmonary edema. The lungs were cooled to 20°C; tiny red aggregates formed again in the perfusate. Ex vivo CT scan showed areas of pulmonary edema and a pyramidal right middle lobe opacity. Dissection showed multiple pulmonary emboli-the likely cause of death. However, histology showed agglutinated red blood cells in the microvasculature in pre- and post-EVLP biopsies, which may have contributed to inadequate parenchymal preservation. Organ donors with cold agglutinins may not be suitable owing to the impact of hypothermic preservation. Copyright © 2017 Elsevier Inc. All rights reserved.

Netarsudil Increases Outflow Facility in Human Eyes Through Multiple Mechanisms

PubMed Central

Ren, Ruiyi; Li, Guorong; Le, Thuy Duong; Kopczynski, Casey; Stamer, W. Daniel; Gong, Haiyan

2016-01-01

Purpose Netarsudil is a Rho kinase/norepinephrine transporter inhibitor currently in phase 3 clinical development for glaucoma treatment. We investigated the effects of its active metabolite, netarsudil-M1, on outflow facility (C), outflow hydrodynamics, and morphology of the conventional outflow pathway in enucleated human eyes. Methods Paired human eyes (n = 5) were perfused with either 0.3 μM netarsudil-M1 or vehicle solution at constant pressure (15 mm Hg). After 3 hours, fluorescent microspheres were added to perfusion media to trace the outflow patterns before perfusion-fixation. The percentage effective filtration length (PEFL) was calculated from the measured lengths of tracer distribution in the trabecular meshwork (TM), episcleral veins (ESVs), and along the inner wall (IW) of Schlemm's canal after global and confocal imaging. Morphologic changes along the trabecular outflow pathway were investigated by confocal, light, and electron microscopy. Results Perfusion with netarsudil-M1 significantly increased C when compared to baseline (51%, P < 0.01) and to paired controls (102%, P < 0.01), as well as significantly increased PEFL in both IW (P < 0.05) and ESVs (P < 0.01). In treated eyes, PEFL was significantly higher in ESVs than in the IW (P < 0.01) and was associated with increased cross-sectional area of ESVs (P < 0.01). Percentage effective filtration length in ESVs positively correlated with the percentage change in C (R2 = 0.58, P = 0.01). A significant increase in juxtacanalicular connective tissue (JCT) thickness (P < 0.05) was found in treated eyes compared to controls. Conclusions Netarsudil acutely increased C by expansion of the JCT and dilating the ESVs, which led to redistribution of aqueous outflow through a larger area of the IW and ESVs. PMID:27842161

Brain dialysis: in vivo metabolism of dopamine and serotonin by monoamine oxidase A but not B in the striatum of unrestrained rats.

PubMed

Kato, T; Dong, B; Ishii, K; Kinemuchi, H

1986-04-01

A dialysis cannula was implanted into rat striatum while the animals were anesthetized, and the area was perfused with Ringer solution while the animals were unanesthetized after at least 3 days following surgery. Concentrations of the metabolites of 3,4-dihydroxyphenylethylamine (DA) and 5-hydroxytryptamine (5-HT) in the perfusate were determined by HPLC with electrochemical detection. Levels of the DA metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the perfusate significantly decreased after pargyline administration (50 mg/kg i.p.), which may inhibit not only monoamine oxidase (MAO)-B but also MAO-A in these high doses. The level of the 5-HT metabolite 5-hydroxyindoleacetic acid (5-HIAA) also decreased after pargyline treatment, although change in the relative level of 5-HIAA was less than that of DOPAC or HVA. To clarify the mechanisms for the metabolism of monoamines in rat striatum, highly specific MAO-A and -B inhibitors were used in the following experiments. Treatment with l-deprenyl (10 mg/kg), a specific inhibitor for MAO-B, did not cause any statistically significant change in DOPAC, HVA, and 5-HIAA levels. No significant change was found in rat striatal homogenates at 2 h after the same treatment with l-deprenyl. In contrast, low-dose treatment (1 mg/kg) with clorgyline, a specific inhibitor for MAO-A, caused a significant decrease in levels of these three metabolites in both the perfusates and tissue homogenates. In addition to the above three metabolites, the level of 3-methoxytyramine, which is an indicator of the amount of DA released, greatly increased after treatment with a low dose (1 mg/kg) of clorgyline.(ABSTRACT TRUNCATED AT 250 WORDS)

Distal tubule bicarbonate reabsorption in NH4Cl acidotic rats.

PubMed

Vandorpe, D H; Levine, D Z

1989-08-01

NH4Cl acidosis--a common experimental model of hyperchloremic metabolic acidosis--elicits complex intrarenal responses whereby the fall in plasma bicarbonate concentration can be restored to normal after the initial acid load. Using the technique of in vivo micropuncture of surface distal tubules of the rat kidney, we attempted to further define controlling mechanisms underlying the enhanced bicarbonate reabsorption in this setting. Specifically, we wished to determine the dependence of distal tubule bicarbonate reabsorption (JtCO2) on sodium transport, water reabsorption, and carbonic anhydrase activity. Surface distal tubules of Sprague-Dawley rats made acidotic by ammonium chloride gavage (arterial blood pH: 7.15 +/- 0.01, [HCO3]: 14.8 +/- 0.5 mM) were perfused in vivo at 8 and 24 nL/min with 4 different isoosmotic, 25 mM bicarbonate solutions: Group 1 was perfused with 60 mM Na, Group 2 with 60 mM choline, Group 3 with 60 mM choline + 3 x 10(-4) M amiloride, and Group 4 with 60 mM Na + 10(-3) M acetazolamide. At 8 nL/min, significant bicarbonate reabsorption occurred with all perfusates. JtCO2 was 65 +/- 4, 59 +/- 5, 58 +/- 6, and 40 +/- 4 pmol.min-1.mm-1, in Groups 1, 2, 3, and 4, respectively. However, JtCO2 in Group 4 was significantly less than that in Groups 1 and 2 (p less than 0.01 and p less than 0.05, respectively). Amiloride added to the low sodium perfusate did not reduce bicarbonate reabsorption. We conclude that bicarbonate reabsorption in distal tubules of acidotic rats is acetazolamide-sensitive and is not significantly sustained by sodium or water movements.

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

Oxygen-charged HTK-F6H8 emulsion reduces ischemia-reperfusion injury in kidneys from brain-dead pigs.

PubMed

Asif, Sana; Sedigh, Amir; Nordström, Johan; Brandhorst, Heide; Jorns, Carl; Lorant, Tomas; Larsson, Erik; Magnusson, Peetra U; Nowak, Greg; Theisinger, Sonja; Hoeger, Simone; Wennberg, Lars; Korsgren, Olle; Brandhorst, Daniel

2012-12-01

Prolonged cold ischemia is frequently associated with a greater risk of delayed graft function and enhanced graft failure. We hypothesized that media, combining a high oxygen-dissolving capacity with specific qualities of organ preservation solutions, would be more efficient in reducing immediate ischemia-reperfusion injury from organs stored long term compared with standard preservation media. Kidneys retrieved from brain-dead pigs were flushed using either cold histidine-tryptophan-ketoglutarate (HTK) or oxygen-precharged emulsion composed of 75% HTK and 25% perfluorohexyloctane. After 18 h of cold ischemia the kidneys were transplanted into allogeneic recipients and assessed for adenosine triphosphate content, morphology, and expression of genes related to hypoxia, environmental stress, inflammation, and apoptosis. Compared with HTK-flushed kidneys, organs preserved using oxygen-precharged HTK-perfluorohexyloctane emulsion had increased elevated adenosine triphosphate content and a significantly lower gene expression of hypoxia inducible factor-1α, vascular endothelial growth factor, interleukin-1α, tumor necrosis factor-α, interferon-α, JNK-1, p38, cytochrome-c, Bax, caspase-8, and caspase-3 at all time points assessed. In contrast, the mRNA expression of Bcl-2 was significantly increased. The present study has demonstrated that in brain-dead pigs the perfusion of kidneys with oxygen-precharged HTK-perfluorohexyloctane emulsion results in significantly reduced inflammation, hypoxic injury, and apoptosis and cellular integrity and energy content are well maintained. Histologic examination revealed less tubular, vascular, and glomerular changes in the emulsion-perfused tissue compared with the HTK-perfused counterparts. The concept of perfusing organs with oxygen-precharged emulsion based on organ preservation media represents an efficient alternative for improved organ preservation. Copyright © 2012 Elsevier Inc. All rights reserved.

The effect of the K+ agonist nicorandil on peripheral vascular resistance.

PubMed

Brodmann, Marianne; Lischnig, Ulrike; Lueger, Andreas; Stark, Gerhard; Pilger, Ernst

2006-07-28

The vasoactive effect of nicorandil on coronary arteries is well known. Nicorandil exerts its vasodilatory effect through a dual mechanism of action: involving on the one hand cyclic guanosine monophosphate (c GMP) as a nitrovasodilatator, and on the other hand, acting as a potassium channel opener. To address the question if nicorandil works in peripheral arteries, its effect on peripheral vascular resistance was evaluated in isolated perfused guinea pig hind limbs. A catheter was inserted via the distal aorta and common iliac artery. Perfusion pressure was monitored under constant perfusion with Tyrode's solution, therefore changes in perfusion pressure represent changes in vascular resistance. After stabilization precontraction of the peripheral vascular bed was achieved with noradrenaline 3 microM and nicorandil was added in concentrations of 1, 10 and 100 microM. The effect of nicorandil (1, 10 and 100 microM) was tested in the presence of L-NAME and glybenclamide. A significant reduction of vascular peripheral resistance was already achieved at a concentration of 1 microM nicorandil (30.3+/-6.1%, mean S.E.M., p < 0.001). At a concentration of 100 microM nicorandil the reduction of peripheral vascular resistance was 94.4+/-16.4%. Peripheral vascular resistance was less but nearly comparable reduced by nicorandil (100 microM) if the endothelial NO effect was inhibited by L-NAME (58.6+/-18.6%) or if the ATP-dependent potassium channels were blocked by glybenclamide (56.4+/-14.6%). In peripheral arteries the nitrovasodilator effect of nicorandil is nearly comparable to the potassium agonistic effect, and the concentration, which is necessary to reduce peripheral vascular resistance significantly, is comparable with dosages necessary for reduction of coronary resistance.

A microperfusion study of sucrose movement across the rat proximal tubule during renal vein constriction

PubMed Central

Bank, Norman; Yarger, William E.; Aynedjian, Hagop S.

1971-01-01

Constriction of the renal vein has been shown to inhibit net sodium and water reabsorption by the rat proximal tubule. The mechanism is unknown but might be the result of inhibition of the active sodium pump induced by changes in the interstitial fluid compartment of the kidney, or to enhanced passive backflux of sodium and water into the cell or directly into the tubular lumen. Since passive movement of solutes across epithelial membranes is determined in part by the permeability characteristics of the epithelium, an increase in the permeability of the proximal tubule during venous constriction would suggest that enhanced passive flux is involved in the inhibition of reabsorption. In the present experiments, isolated segments of rat proximal convoluted tubules were microperfused in vivo with saline while the animals were receiving 14C-labeled sucrose intravenously. In normal control animals, no sucrose was detected in the majority of the collected tubular perfusates. In rats with renal vein constriction (RVC), however, sucrose consistently appeared in the tubular perfusates. The rate of inflow of sucrose correlated with the length of the perfused segment, estimated by fractional water reabsorption. In another group of animals with renal vein constriction, inulin-14C was given intravenously and the proximal tubules similarly microperfused. Inulin did not appear in the majority of collected perfusates in these animals. These observations indicate that a physiological alteration in the permeability of the proximal tubule occurs during RVC. Such an increase in permeability is consistent with the view that enhanced passive extracellular back-flux plays a role in the reduction of net sodium and water reabsorption in this experimental condition. PMID:5540167

Umbilical mesenchymal stromal cells provide intestinal protection through nitric oxide dependent pathways.

PubMed

Jensen, Amanda R; Drucker, Natalie A; Ferkowicz, Michael J; Markel, Troy A

2018-04-01

Umbilical-derived mesenchymal stromal cells (USCs) have shown promise in the protection of ischemic organs. We hypothesized that USCs would improve mesenteric perfusion, preserve intestinal histological architecture, and limit inflammation by nitric oxide-dependent mechanisms following intestinal ischemia/reperfusion (IR) injury. Adult wild-type C57BL/6J (WT) and endothelial nitric oxide synthase knock out (eNOS KO) mice were used: (1) WT IR + vehicle, (2) WT IR + USC, (3) eNOS KO IR + vehicle, and (4) eNOS KO IR + USC. Mice were anesthetized, and a midline laparotomy was performed. The superior mesenteric artery was clamped with a nonoccluding clamp for 60-min. Following IR, mice were treated with an injection of 250 μL phosphate buffered saline or 2 × 10 6 USCs suspended in 250-μL phosphate buffered saline solution. Mesenteric perfusion images were acquired using laser Doppler imaging. Perfusion was analyzed as a percentage of baseline. At 24 h, mice were euthanized, and intestines were harvested. Intestines were evaluated for injury, and data were analyzed using the Mann-Whitney or Kruskal-Wallis tests. Intestinal mesenteric perfusion was significantly improved in WT mice treated with USC therapy compared with eNOS KOs. Intestinal histological architecture was preserved with USC therapy in WT mice. However, in eNOS KO mice, this benefit was abolished. Finally, the presence of several cytokines and growth factors were significantly improved in WT mice compared with eNOS KO mice treated with USCs. The benefits of USC-mediated therapy following intestinal IR injury likely occur via nitric oxide-dependent pathways. Further studies are required to define the molecular mechanisms by which USCs activate endothelial nitric oxide synthase to bring about their protective effects. Copyright © 2017 Elsevier Inc. All rights reserved.

Liposomes as fatty acids carriers in isolated rat liver: effect on energy metabolism and on isolated mitochondria activity.

PubMed

Delmas-Beauvieux, M C; Leducq, N; Thiaudière, E; Diolez, P; Gin, H; Canioni, P; Gallis, J L

2000-02-01

The effects of fatty acids (FA)-carrier, egg-lecithin liposomes (LIPO) as alternative to BSA, on ATP, glycogen and glucose contents in isolated perfused liver of fed rats were non-invasively studied using 31P/13C nuclear magnetic resonance (NMR). Oxidative phosphorylation was studied in isolated mitochondria from the same liver consecutively to the NMR experiments. ATP content decreased slowly and ATP turnover was similar during the perfusion with saline solution (KHB) or LIPO. However, LIPO induced an enhancement of respiratory control ratio in isolated mitochondria. Tissue glycogen and glucose content decreased when FA (linoleate or linolenate) were perfused with defatted BSA (3%) or LIPO (600 mg/l) whereas glucose excretion level was unchanged and lactate excretion tended to increase, reflecting changes in the cytosolic redox state and/or an enhancement of glycolysis. Addition of FA (0.5 or 1.5 mM) to LIPO caused a dramatic fall in liver ATP, a mitochondrial uncoupling and an impairment of the phosphorylation activity. Perfusion with FA (1.5 mM) carried by BSA significantly increased the ATP degradation without change of mitochondrial function. Owing to the higher affinity of BSA than LIPO for FA, these latter could be more easily released from complex LIPO-FA, increasing their uncoupling effect. Hence, the FA concentrations have to be largely decreased from the above currently used concentrations to avoid this effect. It will then be possible to minimize the effector action of FA and to study their more specific metabolic function as fuel. It was concluded that LIPO were appropriate carriers to study the different metabolic effects of FA.

Computed Tomography and Optical Imaging of Osteogenesis-angiogenesis Coupling to Assess Integration of Cranial Bone Autografts and Allografts.

PubMed

Cohn Yakubovich, Doron; Tawackoli, Wafa; Sheyn, Dmitriy; Kallai, Ilan; Da, Xiaoyu; Pelled, Gadi; Gazit, Dan; Gazit, Zulma

2015-12-22

A major parameter determining the success of a bone-grafting procedure is vascularization of the area surrounding the graft. We hypothesized that implantation of a bone autograft would induce greater bone regeneration by abundant blood vessel formation. To investigate the effect of the graft on neovascularization at the defect site, we developed a micro-computed tomography (µCT) approach to characterize newly forming blood vessels, which involves systemic perfusion of the animal with a polymerizing contrast agent. This method enables detailed vascular analysis of an organ in its entirety. Additionally, blood perfusion was assessed using fluorescence imaging (FLI) of a blood-borne fluorescent agent. Bone formation was quantified by FLI using a hydroxyapatite-targeted probe and µCT analysis. Stem cell recruitment was monitored by bioluminescence imaging (BLI) of transgenic mice that express luciferase under the control of the osteocalcin promoter. Here we describe and demonstrate preparation of the allograft, calvarial defect surgery, µCT scanning protocols for the neovascularization study and bone formation analysis (including the in vivo perfusion of contrast agent), and the protocol for data analysis. The 3D high-resolution analysis of vasculature demonstrated significantly greater angiogenesis in animals with implanted autografts, especially with respect to arteriole formation. Accordingly, blood perfusion was significantly higher in the autograft group by the 7(th) day after surgery. We observed superior bone mineralization and measured greater bone formation in animals that received autografts. Autograft implantation induced resident stem cell recruitment to the graft-host bone suture, where the cells differentiated into bone-forming cells between the 7(th) and 10(th) postoperative day. This finding means that enhanced bone formation may be attributed to the augmented vascular feeding that characterizes autograft implantation. The methods depicted may serve as an optimal tool to study bone regeneration in terms of tightly bounded bone formation and neovascularization.

Interrupted infusion of echocardiographic contrast as a basis for accurate measurement of myocardial perfusion: ex vivo validation and analysis procedures.

PubMed

Toledo, Eran; Collins, Keith A; Williams, Ursula; Lammertin, Georgeanne; Bolotin, Gil; Raman, Jai; Lang, Roberto M; Mor-Avi, Victor

2005-12-01

Echocardiographic quantification of myocardial perfusion is based on analysis of contrast replenishment after destructive high-energy ultrasound impulses (flash-echo). This technique is limited by nonuniform microbubble destruction and the dependency on exponential fitting of a small number of noisy time points. We hypothesized that brief interruptions of contrast infusion (ICI) would result in uniform contrast clearance followed by slow replenishment and, thus, would allow analysis from multiple data points without exponential fitting. Electrocardiographic-triggered images were acquired in 14 isolated rabbit hearts (Langendorff) at 3 levels of coronary flow (baseline, 50%, and 15%) during contrast infusion (Definity) with flash-echo and with a 20-second infusion interruption. Myocardial videointensity was measured over time from flash-echo sequences, from which characteristic constant beta was calculated using an exponential fit. Peak contrast inflow rate was calculated from ICI data using analysis of local time derivatives. Computer simulations were used to investigate the effects of noise on the accuracy of peak contrast inflow rate and beta calculations. ICI resulted in uniform contrast clearance and baseline replenishment times of 15 to 25 cardiac cycles. Calculated peak contrast inflow rate followed the changes in coronary flow in all hearts at both levels of reduced flow (P < .05) and had a low intermeasurement variability of 7 +/- 6%. With flash-echo, contrast clearance was less uniform and baseline replenishment times were only 4 to 6 cardiac cycles. beta Decreased significantly only at 15% flow, and had intermeasurement variability of 42 +/- 33%. Computer simulations showed that measurement errors in both perfusion indices increased with noise, but beta had larger errors at higher rates of contrast inflow. ICI provides the basis for accurate and reproducible quantification of myocardial perfusion using fast and robust numeric analysis, and may constitute an alternative to the currently used techniques.

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.

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.

Abnormal regional cerebral blood flow in childhood autism.

PubMed

Ohnishi, T; Matsuda, H; Hashimoto, T; Kunihiro, T; Nishikawa, M; Uema, T; Sasaki, M

2000-09-01

Neuroimaging studies of autism have shown abnormalities in the limbic system and cerebellar circuits and additional sites. These findings are not, however, specific or consistent enough to build up a coherent theory of the origin and nature of the brain abnormality in autistic patients. Twenty-three children with infantile autism and 26 non-autistic controls matched for IQ and age were examined using brain-perfusion single photon emission computed tomography with technetium-99m ethyl cysteinate dimer. In autistic subjects, we assessed the relationship between regional cerebral blood flow (rCBF) and symptom profiles. Images were anatomically normalized, and voxel-by-voxel analyses were performed. Decreases in rCBF in autistic patients compared with the control group were identified in the bilateral insula, superior temporal gyri and left prefrontal cortices. Analysis of the correlations between syndrome scores and rCBF revealed that each syndrome was associated with a specific pattern of perfusion in the limbic system and the medial prefrontal cortex. The results confirmed the associations of (i) impairments in communication and social interaction that are thought to be related to deficits in the theory of mind (ToM) with altered perfusion in the medial prefrontal cortex and anterior cingulate gyrus, and (ii) the obsessive desire for sameness with altered perfusion in the right medial temporal lobe. The perfusion abnormalities seem to be related to the cognitive dysfunction observed in autism, such as deficits in ToM, abnormal responses to sensory stimuli, and the obsessive desire for sameness. The perfusion patterns suggest possible locations of abnormalities of brain function underlying abnormal behaviour patterns in autistic individuals.

Optimization of culture conditions for osteogenically-induced mesenchymal stem cells in β-tricalcium phosphate ceramics with large interconnected channels.

PubMed

Bernhardt, Anne; Lode, Anja; Peters, Fabian; Gelinsky, Michael

2011-06-01

The aim of this study was to optimize culture conditions for human mesenchymal stem cells (hMSCs) in β-tricalcium phosphate ceramics with large interconnected channels. Fully interconnected macrochannels comprising pore diameters of 750 µm and 1400 µm were inserted into microporous β-tricalcium phosphate (β-TCP) scaffolds by milling. Human bone marrow-derived MSCs were seeded into the scaffolds and cultivated for up to 3 weeks in both static and perfusion culture in the presence of osteogenic supplements (dexamethasone, β-glycerophosphate, ascorbate). It was confirmed by scanning electron microscopic investigations and histological staining that the perfusion culture resulted in uniform distribution of cells inside the whole channel network, whereas the statically cultivated cells were primarily found at the surface of the ceramic samples. It was also determined that perfusion with standard medium containing 10% fetal calf serum (FCS) led to a strong increase (seven-fold) of cell numbers compared with static cultivation observed after 3 weeks. Perfusion with low-serum medium (2% FCS) resulted in moderate proliferation rates which were comparable to those achieved in static culture, although the specific alkaline phosphatase (ALP) activity increased by a factor of more than 3 compared to static cultivation. Gene expression analysis of the ALP gene also revealed higher levels of ALP mRNA in low-serum perfused samples compared to statically cultivated constructs. In contrast, gene expression of the late osteogenic marker bone sialoprotein II (BSPII) was decreased for perfused samples compared to statically cultivated samples. Copyright © 2010 John Wiley & Sons, Ltd.

SPECT neuroimaging and neuropsychological functions in different stages of Parkinson's disease.

PubMed

Paschali, Anna; Messinis, Lambros; Kargiotis, Odysseas; Lakiotis, Velissarios; Kefalopoulou, Zinovia; Constantoyannis, Costantinos; Papathanasopoulos, Panagiotis; Vassilakos, Pavlos

2010-06-01

The present study investigated differences and associations between cortical perfusion, nigrostriatal dopamine pathway and neuropsychological functions in different stages of Parkinson's disease (PD). We recruited 53 non-demented PD patients divided into four groups according to the Hoehn and Yahr (HY) staging system and 20 healthy controls who were used in the comparison of the neuropsychological findings. Each patient underwent two separate brain single photon emission computed tomography (SPECT) studies (perfusion and dopamine transporter binding) as well as neuropsychological evaluation. Perfusion images of each patient were quantified and compared with a normative database provided by the NeuroGam software manufacturers. Mean values obtained from the cortical areas and neuropsychological measures in the different groups were also compared by analysis of covariance (ANCOVA) controlling for disease duration and educational level. We found cognitive deficits especially in the late PD stages (HY 3, 4 and 5) compared to the early stages (HY 1 and 2) and associations between cognitive decrements and cortical perfusion deterioration mainly in the frontal and posterior cortical areas. Compared with controls, PD patients showed impairments of cognition and cerebral perfusion that increased with clinical severity. Furthermore, we found a significant correlation between the performance on the phonemic fluency task and regional cerebral blood flow (rCBF) in the left frontal lobe. Dopamine transporter binding in the left caudate nucleus significantly correlated with blood flow in the left dorsolateral prefrontal cortex (DLPFC), but not with measures of executive functions. There are significant cognitive and perfusion deficits associated with PD progression, implying a multifactorial neurodegeneration process apart from dopamine depletion in the substantia nigra pars compacta (SNc).

Heterogeneity of pulmonary perfusion as a mechanistic image-based phenotype in emphysema susceptible smokers.

PubMed

Alford, Sara K; van Beek, Edwin J R; McLennan, Geoffrey; Hoffman, Eric A

2010-04-20

Recent evidence suggests that endothelial dysfunction and pathology of pulmonary vascular responses may serve as a precursor to smoking-associated emphysema. Although it is known that emphysematous destruction leads to vasculature changes, less is known about early regional vascular dysfunction which may contribute to and precede emphysematous changes. We sought to test the hypothesis, via multidetector row CT (MDCT) perfusion imaging, that smokers showing early signs of emphysema susceptibility have a greater heterogeneity in regional perfusion parameters than emphysema-free smokers and persons who had never smoked (NS). Assuming that all smokers have a consistent inflammatory response, increased perfusion heterogeneity in emphysema-susceptible smokers would be consistent with the notion that these subjects may have the inability to block hypoxic vasoconstriction in patchy, small regions of inflammation. Dynamic ECG-gated MDCT perfusion scans with a central bolus injection of contrast were acquired in 17 NS, 12 smokers with normal CT imaging studies (SNI), and 12 smokers with subtle CT findings of centrilobular emphysema (SCE). All subjects had normal spirometry. Quantitative image analysis determined regional perfusion parameters, pulmonary blood flow (PBF), and mean transit time (MTT). Mean and coefficient of variation were calculated, and statistical differences were assessed with one-way ANOVA. MDCT-based MTT and PBF measurements demonstrate globally increased heterogeneity in SCE subjects compared with NS and SNI subjects but demonstrate similarity between NS and SNI subjects. These findings demonstrate a functional lung-imaging measure that provides a more mechanistically oriented phenotype that differentiates smokers with and without evidence of emphysema susceptibility.

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.

Laser Doppler flowmetry evaluation of gingival recovery response after laser treatment

NASA Astrophysics Data System (ADS)

Todea, Carmen; Cânjǎu, Silvana; Dodenciu, Dorin; Miron, Mariana I.; Tudor, Anca; Bǎlǎbuc, Cosmin

2013-06-01

This study was performed in order to evaluate in vivo the applicability of Laser Doppler Flowmetry (LDF) in recording the gingival blood flow and to assess the changes of gingival blood flow following gingival reshaping performed with Er:YAG and 980 nm diode lasers. The LDF evaluation was performed on 20 anterior teeth, which underwent reshaping of gingiva, corresponding to 5 female patients (4 anterior teeth/patient), aged between 20 and 35. One part of the mouth was treated with Er:YAG laser (LP, VLP modes, 140 - 250 mJ, 10 - 20 Hz, using cylindrical sapphire tips) and other part with 980 nm diode laser (CW, 4 W, contact mode and saline solution cooling). The gingival blood flow was monitored using a MoorLab laser Doppler equipment (Moor Instruments Ltd., Axminster, UK) with a straight optical probe, MP3b, 10 mm. The data were processed using statistical analysis software SPSS v16.0.1. The investigation showed an evident decrease in perfusion for both areas in comparison with the baseline values 24 hours after treatment. The microvascular blood flow increased significantly after 7 days in both areas but mostly in diode area (p<0.001). After 14 days for the Er:YAG area the blood perfusion returned to the initial value. The results in diode area remained at a high level after 14 days. Both lasers proved efficiency in the surgical treatment of gingival tissue. Moreover, Laser Doppler Flowmetry is adequate for recording changes in gingival blood flow following periodontal surgery.

Thienoquinolins exert diuresis by strongly inhibiting UT-A urea transporters

PubMed Central

Ren, Huiwen; Wang, Yanhua; Xing, Yongning; Ran, Jianhua; Liu, Ming; Lei, Tianluo; Zhou, Hong; Li, Runtao; Sands, Jeff M.

2014-01-01

Urea transporters (UT) play an important role in the urine concentration mechanism by mediating intrarenal urea recycling, suggesting that UT inhibitors could have therapeutic use as a novel class of diuretic. Recently, we found a thienoquinolin UT inhibitor, PU-14, that exhibited diuretic activity. The purpose of this study was to identify more potent UT inhibitors that strongly inhibit UT-A isoforms in the inner medullary collecting duct (IMCD). Efficient thienoquinolin UT inhibitors were identified by structure-activity relationship analysis. Urea transport inhibition activity was assayed in perfused rat terminal IMCDs. Diuretic activity of the compound was determined in rats and mice using metabolic cages. The results show that the compound PU-48 exhibited potent UT-A inhibition activity. The inhibition was 69.5% with an IC50 of 0.32 μM. PU-48 significantly inhibited urea transport in perfused rat terminal IMCDs. PU-48 caused significant diuresis in UT-B null mice, which indicates that UT-A is the target of PU-48. The diuresis caused by PU-48 did not change blood Na+, K+, or Cl− levels or nonurea solute excretion in rats and mice. No toxicity was detected in cells or animals treated with PU-48. The results indicate that thienoquinolin UT inhibitors induce a diuresis by inhibiting UT-A in the IMCD. This suggests that they may have the potential to be developed as a novel class of diuretics with fewer side effects than classical diuretics. PMID:25298523

Thienoquinolins exert diuresis by strongly inhibiting UT-A urea transporters.

PubMed

Ren, Huiwen; Wang, Yanhua; Xing, Yongning; Ran, Jianhua; Liu, Ming; Lei, Tianluo; Zhou, Hong; Li, Runtao; Sands, Jeff M; Yang, Baoxue

2014-12-15

Urea transporters (UT) play an important role in the urine concentration mechanism by mediating intrarenal urea recycling, suggesting that UT inhibitors could have therapeutic use as a novel class of diuretic. Recently, we found a thienoquinolin UT inhibitor, PU-14, that exhibited diuretic activity. The purpose of this study was to identify more potent UT inhibitors that strongly inhibit UT-A isoforms in the inner medullary collecting duct (IMCD). Efficient thienoquinolin UT inhibitors were identified by structure-activity relationship analysis. Urea transport inhibition activity was assayed in perfused rat terminal IMCDs. Diuretic activity of the compound was determined in rats and mice using metabolic cages. The results show that the compound PU-48 exhibited potent UT-A inhibition activity. The inhibition was 69.5% with an IC50 of 0.32 μM. PU-48 significantly inhibited urea transport in perfused rat terminal IMCDs. PU-48 caused significant diuresis in UT-B null mice, which indicates that UT-A is the target of PU-48. The diuresis caused by PU-48 did not change blood Na(+), K(+), or Cl(-) levels or nonurea solute excretion in rats and mice. No toxicity was detected in cells or animals treated with PU-48. The results indicate that thienoquinolin UT inhibitors induce a diuresis by inhibiting UT-A in the IMCD. This suggests that they may have the potential to be developed as a novel class of diuretics with fewer side effects than classical diuretics. Copyright © 2014 the American Physiological Society.

Automated Quantitative Nuclear Cardiology Methods

PubMed Central

Motwani, Manish; Berman, Daniel S.; Germano, Guido; Slomka, Piotr J.

2016-01-01

Quantitative analysis of SPECT and PET has become a major part of nuclear cardiology practice. Current software tools can automatically segment the left ventricle, quantify function, establish myocardial perfusion maps and estimate global and local measures of stress/rest perfusion – all with minimal user input. State-of-the-art automated techniques have been shown to offer high diagnostic accuracy for detecting coronary artery disease, as well as predict prognostic outcomes. This chapter briefly reviews these techniques, highlights several challenges and discusses the latest developments. PMID:26590779

Added Value of Assessing Adnexal Masses with Advanced MRI Techniques

PubMed Central

Thomassin-Naggara, I.; Balvay, D.; Rockall, A.; Carette, M. F.; Ballester, M.; Darai, E.; Bazot, M.

2015-01-01

This review will present the added value of perfusion and diffusion MR sequences to characterize adnexal masses. These two functional MR techniques are readily available in routine clinical practice. We will describe the acquisition parameters and a method of analysis to optimize their added value compared with conventional images. We will then propose a model of interpretation that combines the anatomical and morphological information from conventional MRI sequences with the functional information provided by perfusion and diffusion weighted sequences. PMID:26413542

Application of in situ ductal perfusion to facilitate isolation of high-quality RNA from mouse pancreas.

PubMed

Mullin, Anne E; Soukatcheva, Galina; Verchere, C Bruce; Chantler, Janet K

2006-05-01

A technique to isolate high-quality intact RNA from murine pancreas is described. This technique involves in situ ductal perfusion of the pancreas with an RNase inhibitor prior to removal of the organ for RNA extraction. In this way, the pancreatic RNases are inhibited in situ allowing good yields of intact RNA, suitable for studies on pancreatic gene transcription by real-time PCR or microarray analysis, to be obtained in a reliable way.

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

PubMed

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

2017-01-01

Purpose : To evaluate the feasibility of a simplified method based on diffusion-weighted imaging (DWI) acquired with three b -values to measure tissue perfusion linked to microcirculation, to validate it against from perfusion-related parameters derived from intravoxel incoherent motion (IVIM) and dynamic contrast-enhanced (DCE) magnetic resonance (MR) imaging, and to investigate its utility to differentiate low- from high-grade gliomas. Materials and Methods : The prospective study was approved by the local institutional review board and written informed consent was obtained from all patients. From May 2016 and May 2017, 50 patients confirmed with glioma were assessed with multi- b -value DWI and DCE MR imaging at 3.0 T. Besides conventional apparent diffusion coefficient (ADC 0,1000 ) map, perfusion-related parametric maps for IVIM-derived perfusion fraction ( f ) and pseudodiffusion coefficient (D*), DCE MR imaging-derived pharmacokinetic metrics, including K trans , v e and v p , as well as a metric named simplified perfusion fraction (SPF), were generated. Correlation between perfusion-related parameters was analyzed by using the Spearman rank correlation. All imaging parameters were compared between the low-grade ( n = 19) and high-grade ( n = 31) groups by using the Mann-Whitney U test. The diagnostic performance for tumor grading was evaluated with receiver operating characteristic (ROC) analysis. Results : SPF showed strong correlation with IVIM-derived f and D* ( ρ = 0.732 and 0.716, respectively; both P < 0.001). Compared with f , SPF was more correlated with DCE MR imaging-derived K trans ( ρ = 0.607; P < 0.001) and v p ( ρ = 0.397; P = 0.004). Among all parameters, SPF achieved the highest accuracy for differentiating low- from high-grade gliomas, with an area under the ROC curve value of 0.942, which was significantly higher than that of ADC 0,1000 ( P = 0.004). By using SPF as a discriminative index, the diagnostic sensitivity and specificity were 87.1% and 94.7%, respectively, at the optimal cut-off value of 19.26%. Conclusion : The simplified method to measure tissue perfusion based on DWI by using three b -values may be helpful to differentiate low- from high-grade gliomas. SPF may serve as a valuable alternative to measure tumor perfusion in gliomas in a noninvasive, convenient and efficient way.

Hyperintense Vessels on T2-PROPELLER-FLAIR in Patients with Acute MCA Stroke: Prediction of Arterial Stenosis and Perfusion Abnormality.

PubMed

Ahn, S J; Suh, S H; Lee, K-Y; Kim, J H; Seo, K-D; Lee, S

2015-11-01

Fluid-attenuated inversion recovery hyperintense vessels in stroke represent leptomeningeal collateral flow. We presumed that FLAIR hyperintense vessels would be more closely associated with arterial stenosis and perfusion abnormality in ischemic stroke on T2-PROPELLER-FLAIR than on T2-FLAIR. We retrospectively reviewed 35 patients with middle cerebral territorial infarction who underwent MR imaging. FLAIR hyperintense vessel scores were graded according to the number of segments with FLAIR hyperintense vessels in the MCA ASPECTS areas. We compared the predictability of FLAIR hyperintense vessels between T2-PROPELLER-FLAIR and T2-FLAIR for large-artery stenosis. The interagreement between perfusion abnormality and FLAIR hyperintense vessels was assessed. In subgroup analysis (9 patients with MCA horizontal segment occlusion), the association of FLAIR hyperintense vessels with ischemic lesion volume and perfusion abnormality volume was evaluated. FLAIR hyperintense vessel scores were significantly higher on T2-PROPELLER-FLAIR than on T2-FLAIR (3.50 ± 2.79 versus 1.21 ± 1.47, P < .01), and the sensitivity for large-artery stenosis was significantly improved on T2-PROPELLER-FLAIR (93% versus 68%, P = .03). FLAIR hyperintense vessels on T2-PROPELLER-FLAIR were more closely associated with perfusion abnormalities than they were on T2-FLAIR (κ = 0.64 and κ = 0.27, respectively). In subgroup analysis, FLAIR hyperintense vessels were positively correlated with ischemic lesion volume on T2-FLAIR, while the mismatch of FLAIR hyperintense vessels between the 2 sequences was negatively correlated with ischemic lesion volume (P = .01). In MCA stroke, FLAIR hyperintense vessels were more prominent on T2-PROPELLER-FLAIR compared with T2-FLAIR. In addition, FLAIR hyperintense vessels on T2-PROPELLER-FLAIR have a significantly higher sensitivity for predicting large-artery stenosis than they do on T2-FLAIR. Moreover, the areas showing FLAIR hyperintense vessels on T2-PROPELLER-FLAIR were more closely associated with perfusion abnormality than those on T2-FLAIR. © 2015 by American Journal of Neuroradiology.

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.

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.

Dual chamber stent prevents organ malperfusion in a model of donation after cardiac death.

PubMed

Tillman, Bryan W; Chun, Youngjae; Cho, Sung Kwon; Chen, Yanfei; Liang, Nathan; Maul, Timothy; Demetris, Anthony; Gu, Xinzhu; Wagner, William R; Tevar, Amit D

2016-10-01

The paradigm for donation after cardiac death subjects donor organs to ischemic injury. A dual-chamber organ perfusion stent would maintain organ perfusion without affecting natural cardiac death. A center lumen allows uninterrupted cardiac blood flow, while an external chamber delivers oxygenated blood to the visceral vessels. A prototype organ perfusion stent was constructed from commercial stents. In a porcine model, the organ perfusion stent was deployed, followed by a simulated agonal period. Oxygenated blood perfused the external stent chamber. Organ perfusion was compared between controls (n = 3) and organ perfusion stent (n = 6). Finally, a custom, nitinol, dual chamber organ perfusion stent was fabricated using a retrievable "petal and stem" design. Endovascular organ perfusion stent deployment achieved visceral isolation without adverse impact on cardiac parameters. Visceral oxygen delivery was 4.8-fold greater compared with controls. During the agonal period, organs in organ perfusion stent-treated animals appeared well perfused in contrast with the malperfused controls. A custom nitinol and polyurethane organ perfusion stent was recaptured easily with simple sheath advancement. An organ perfusion stent maintained organ perfusion during the agonal phase in a porcine model of donation after cardiac death organ donation without adversely affecting cardiac function. Ultimately, the custom retrievable design of this study may help resolve the critical shortage of donor organs for transplant. Copyright © 2016 Elsevier Inc. All rights reserved.

A methodology for generating normal and pathological brain perfusion SPECT images for evaluation of MRI/SPECT fusion methods: application in epilepsy

NASA Astrophysics Data System (ADS)

Grova, C.; Jannin, P.; Biraben, A.; Buvat, I.; Benali, H.; Bernard, A. M.; Scarabin, J. M.; Gibaud, B.

2003-12-01

Quantitative evaluation of brain MRI/SPECT fusion methods for normal and in particular pathological datasets is difficult, due to the frequent lack of relevant ground truth. We propose a methodology to generate MRI and SPECT datasets dedicated to the evaluation of MRI/SPECT fusion methods and illustrate the method when dealing with ictal SPECT. The method consists in generating normal or pathological SPECT data perfectly aligned with a high-resolution 3D T1-weighted MRI using realistic Monte Carlo simulations that closely reproduce the response of a SPECT imaging system. Anatomical input data for the SPECT simulations are obtained from this 3D T1-weighted MRI, while functional input data result from an inter-individual analysis of anatomically standardized SPECT data. The method makes it possible to control the 'brain perfusion' function by proposing a theoretical model of brain perfusion from measurements performed on real SPECT images. Our method provides an absolute gold standard for assessing MRI/SPECT registration method accuracy since, by construction, the SPECT data are perfectly registered with the MRI data. The proposed methodology has been applied to create a theoretical model of normal brain perfusion and ictal brain perfusion characteristic of mesial temporal lobe epilepsy. To approach realistic and unbiased perfusion models, real SPECT data were corrected for uniform attenuation, scatter and partial volume effect. An anatomic standardization was used to account for anatomic variability between subjects. Realistic simulations of normal and ictal SPECT deduced from these perfusion models are presented. The comparison of real and simulated SPECT images showed relative differences in regional activity concentration of less than 20% in most anatomical structures, for both normal and ictal data, suggesting realistic models of perfusion distributions for evaluation purposes. Inter-hemispheric asymmetry coefficients measured on simulated data were found within the range of asymmetry coefficients measured on corresponding real data. The features of the proposed approach are compared with those of other methods previously described to obtain datasets appropriate for the assessment of fusion methods.

Respiratory motion compensation algorithm of ultrasound hepatic perfusion data acquired in free-breathing

NASA Astrophysics Data System (ADS)

Wu, Kaizhi; Zhang, Xuming; Chen, Guangxie; Weng, Fei; Ding, Mingyue

2013-10-01

Images acquired in free breathing using contrast enhanced ultrasound exhibit a periodic motion that needs to be compensated for if a further accurate quantification of the hepatic perfusion analysis is to be executed. In this work, we present an algorithm to compensate the respiratory motion by effectively combining the PCA (Principal Component Analysis) method and block matching method. The respiratory kinetics of the ultrasound hepatic perfusion image sequences was firstly extracted using the PCA method. Then, the optimal phase of the obtained respiratory kinetics was detected after normalizing the motion amplitude and determining the image subsequences of the original image sequences. The image subsequences were registered by the block matching method using cross-correlation as the similarity. Finally, the motion-compensated contrast images can be acquired by using the position mapping and the algorithm was evaluated by comparing the TICs extracted from the original image sequences and compensated image subsequences. Quantitative comparisons demonstrated that the average fitting error estimated of ROIs (region of interest) was reduced from 10.9278 +/- 6.2756 to 5.1644 +/- 3.3431 after compensating.

Thermal Analyses of a Human Kidney and a Rabbit Kidney During Cryopreservation by Vitrification.

PubMed

Ehrlich, Lili E; Fahy, Gregory M; Wowk, Brian G; Malen, Jonathan A; Rabin, Yoed

2018-01-01

This study focuses on thermal analysis of the problem of scaling up from the vitrification of rabbit kidneys to the vitrification of human kidneys, where vitrification is the preservation of biological material in the glassy state. The basis for this study is a successful cryopreservation protocol for a rabbit kidney model, based on using a proprietary vitrification solution known as M22. Using the finite element analysis (FEA) commercial code ANSYS, heat transfer simulations suggest that indeed the rabbit kidney unquestionably cools rapidly enough to be vitrified based on known intrarenal concentrations of M22. Scaling up 21-fold, computer simulations suggest less favorable conditions for human kidney vitrification. In this case, cooling rates below -100 °C are sometimes slower than 1 °C/min, a rate that provides a clear-cut margin of safety at all temperatures based on the stability of rabbit kidneys in past studies. Nevertheless, it is concluded in this study that vitrifying human kidneys is possible without significant ice damage, assuming that human kidneys can be perfused with M22 as effectively as rabbit kidneys. The thermal analysis suggests that cooling rates can be further increased by a careful design of the cryogenic protocol and by tailoring the container to the shape of the kidney, in contrast to the present cylindrical container. This study demonstrates the critical need for the thermal analysis of experimental cryopreservation and highlights the unmet need for measuring the thermophysical properties of cryoprotective solutions under conditions relevant to realistic thermal histories.

Cardiac CT for myocardial ischaemia detection and characterization--comparative analysis.

PubMed

Bucher, A M; De Cecco, C N; Schoepf, U J; Wang, R; Meinel, F G; Binukrishnan, S R; Spearman, J V; Vogl, T J; Ruzsics, B

2014-11-01

The assessment of patients presenting with symptoms of myocardial ischaemia remains one of the most common and challenging clinical scenarios faced by physicians. Current imaging modalities are capable of three-dimensional, functional and anatomical views of the heart and as such offer a unique contribution to understanding and managing the pathology involved. Evidence has accumulated that visual anatomical coronary evaluation does not adequately predict haemodynamic relevance and should be complemented by physiological evaluation, highlighting the importance of functional assessment. Technical advances in CT technology over the past decade have progressively moved cardiac CT imaging into the clinical workflow. In addition to anatomical evaluation, cardiac CT is capable of providing myocardial perfusion parameters. A variety of CT techniques can be used to assess the myocardial perfusion. The single energy first-pass CT and dual energy first-pass CT allow static assessment of myocardial blood pool. Dynamic cardiac CT imaging allows quantification of myocardial perfusion through time-resolved attenuation data. CT-based myocardial perfusion imaging (MPI) is showing promising diagnostic accuracy compared with the current reference modalities. The aim of this review is to present currently available myocardial perfusion techniques with a focus on CT imaging in light of recent clinical investigations. This article provides a comprehensive overview of currently available CT approaches of static and dynamic MPI and presents the results of corresponding clinical trials.

A simultaneous multimodal imaging system for tissue functional parameters

NASA Astrophysics Data System (ADS)

Ren, Wenqi; Zhang, Zhiwu; Wu, Qiang; Zhang, Shiwu; Xu, Ronald

2014-02-01

Simultaneous and quantitative assessment of skin functional characteristics in different modalities will facilitate diagnosis and therapy in many clinical applications such as wound healing. However, many existing clinical practices and multimodal imaging systems are subjective, qualitative, sequential for multimodal data collection, and need co-registration between different modalities. To overcome these limitations, we developed a multimodal imaging system for quantitative, non-invasive, and simultaneous imaging of cutaneous tissue oxygenation and blood perfusion parameters. The imaging system integrated multispectral and laser speckle imaging technologies into one experimental setup. A Labview interface was developed for equipment control, synchronization, and image acquisition. Advanced algorithms based on a wide gap second derivative reflectometry and laser speckle contrast analysis (LASCA) were developed for accurate reconstruction of tissue oxygenation and blood perfusion respectively. Quantitative calibration experiments and a new style of skinsimulating phantom were designed to verify the accuracy and reliability of the imaging system. The experimental results were compared with a Moor tissue oxygenation and perfusion monitor. For In vivo testing, a post-occlusion reactive hyperemia (PORH) procedure in human subject and an ongoing wound healing monitoring experiment using dorsal skinfold chamber models were conducted to validate the usability of our system for dynamic detection of oxygenation and perfusion parameters. In this study, we have not only setup an advanced multimodal imaging system for cutaneous tissue oxygenation and perfusion parameters but also elucidated its potential for wound healing assessment in clinical practice.

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.

Combining Diffusion Tensor Metrics and DSC Perfusion Imaging: Can It Improve the Diagnostic Accuracy in Differentiating Tumefactive Demyelination from High-Grade Glioma?

PubMed

Hiremath, S B; Muraleedharan, A; Kumar, S; Nagesh, C; Kesavadas, C; Abraham, M; Kapilamoorthy, T R; Thomas, B

2017-04-01

Tumefactive demyelinating lesions with atypical features can mimic high-grade gliomas on conventional imaging sequences. The aim of this study was to assess the role of conventional imaging, DTI metrics ( p:q tensor decomposition), and DSC perfusion in differentiating tumefactive demyelinating lesions and high-grade gliomas. Fourteen patients with tumefactive demyelinating lesions and 21 patients with high-grade gliomas underwent brain MR imaging with conventional, DTI, and DSC perfusion imaging. Imaging sequences were assessed for differentiation of the lesions. DTI metrics in the enhancing areas and perilesional hyperintensity were obtained by ROI analysis, and the relative CBV values in enhancing areas were calculated on DSC perfusion imaging. Conventional imaging sequences had a sensitivity of 80.9% and specificity of 57.1% in differentiating high-grade gliomas ( P = .049) from tumefactive demyelinating lesions. DTI metrics ( p : q tensor decomposition) and DSC perfusion demonstrated a statistically significant difference in the mean values of ADC, the isotropic component of the diffusion tensor, the anisotropic component of the diffusion tensor, the total magnitude of the diffusion tensor, and rCBV among enhancing portions in tumefactive demyelinating lesions and high-grade gliomas ( P ≤ .02), with the highest specificity for ADC, the anisotropic component of the diffusion tensor, and relative CBV (92.9%). Mean fractional anisotropy values showed no significant statistical difference between tumefactive demyelinating lesions and high-grade gliomas. The combination of DTI and DSC parameters improved the diagnostic accuracy (area under the curve = 0.901). Addition of a heterogeneous enhancement pattern to DTI and DSC parameters improved it further (area under the curve = 0.966). The sensitivity increased from 71.4% to 85.7% after the addition of the enhancement pattern. DTI and DSC perfusion add profoundly to conventional imaging in differentiating tumefactive demyelinating lesions and high-grade gliomas. The combination of DTI metrics and DSC perfusion markedly improved diagnostic accuracy. © 2017 by American Journal of Neuroradiology.

Solitary pulmonary nodules: Comparison of dynamic first-pass contrast-enhanced perfusion area-detector CT, dynamic first-pass contrast-enhanced MR imaging, and FDG PET/CT.

PubMed

Ohno, Yoshiharu; Nishio, Mizuho; Koyama, Hisanobu; Seki, Shinichiro; Tsubakimoto, Maho; Fujisawa, Yasuko; Yoshikawa, Takeshi; Matsumoto, Sumiaki; Sugimura, Kazuro

2015-02-01

To prospectively compare the capabilities of dynamic perfusion area-detector computed tomography (CT), dynamic magnetic resonance (MR) imaging, and positron emission tomography (PET) combined with CT (PET/CT) with use of fluorine 18 fluorodeoxyglucose (FDG) for the diagnosis of solitary pulmonary nodules. The institutional review board approved this study, and written informed consent was obtained from each subject. A total of 198 consecutive patients with 218 nodules prospectively underwent dynamic perfusion area-detector CT, dynamic MR imaging, FDG PET/CT, and microbacterial and/or pathologic examinations. Nodules were classified into three groups: malignant nodules (n = 133) and benign nodules with low (n = 53) or high (n = 32) biologic activity. Total perfusion was determined with dual-input maximum slope models at area-detector CT, maximum and slope of enhancement ratio at MR imaging, and maximum standardized uptake value (SUVmax) at PET/CT. Next, all indexes for malignant and benign nodules were compared with the Tukey honest significant difference test. Then, receiver operating characteristic analysis was performed for each index. Finally, sensitivity, specificity, and accuracy were compared with the McNemar test. All indexes showed significant differences between malignant nodules and benign nodules with low biologic activity (P < .0001). The area under the receiver operating characteristic curve for total perfusion was significantly larger than that for other indexes (.0006 ≤ P ≤ .04). The specificity and accuracy of total perfusion were significantly higher than those of maximum relative enhancement ratio (specificity, P < .0001; accuracy, P < .0001), slope of enhancement ratio (specificity, P < .0001; accuracy, P < .0001), and SUVmax (specificity, P < .0001; accuracy, P < .0001). Dynamic perfusion area-detector CT is more specific and accurate than dynamic MR imaging and FDG PET/CT in the diagnosis of solitary pulmonary nodules in routine clinical practice. © RSNA, 2014.

Cerebral Perfusion and Gray Matter Changes Associated With Chemotherapy-Induced Peripheral Neuropathy.

PubMed

Nudelman, Kelly N H; McDonald, Brenna C; Wang, Yang; Smith, Dori J; West, John D; O'Neill, Darren P; Zanville, Noah R; Champion, Victoria L; Schneider, Bryan P; Saykin, Andrew J

2016-03-01

To investigate the longitudinal relationship between chemotherapy-induced peripheral neuropathy (CIPN) symptoms (sx) and brain perfusion changes in patients with breast cancer. Interaction of CIPN-sx perfusion effects with known chemotherapy-associated gray matter density decrease was also assessed to elucidate the relationship between CIPN and previously reported cancer treatment-related brain structural changes. Patients with breast cancer treated with (n = 24) or without (n = 23) chemotherapy underwent clinical examination and brain magnetic resonance imaging at the following three time points: before treatment (baseline), 1 month after treatment completion, and 1 year after the 1-month assessment. CIPN-sx were evaluated with the self-reported Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity four-item sensory-specific scale. Perfusion and gray matter density were assessed using voxel-based pulsed arterial spin labeling and morphometric analyses and tested for association with CIPN-sx in the patients who received chemotherapy. Patients who received chemotherapy reported significantly increased CIPN-sx from baseline to 1 month, with partial recovery by 1 year (P < .001). CIPN-sx increase from baseline to 1 month was significantly greater for patients who received chemotherapy compared with those who did not (P = .001). At 1 month, neuroimaging showed that for the group that received chemotherapy, CIPN-sx were positively associated with cerebral perfusion in the right superior frontal gyrus and cingulate gyrus, regions associated with pain processing (P < .001). Longitudinal magnetic resonance imaging analysis in the group receiving chemotherapy indicated that CIPN-sx and associated perfusion changes from baseline to 1 month were also positively correlated with gray matter density change (P < .005). Peripheral neuropathy symptoms after systemic chemotherapy for breast cancer are associated with changes in cerebral perfusion and gray matter. The specific mechanisms warrant further investigation given the potential diagnostic and therapeutic implications. © 2015 by American Society of Clinical Oncology.

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 hemodynamic pathophysiology in glaucoma.

Cerebral Perfusion and Gray Matter Changes Associated With Chemotherapy-Induced Peripheral Neuropathy

PubMed Central

Nudelman, Kelly N.H.; McDonald, Brenna C.; Wang, Yang; Smith, Dori J.; West, John D.; O'Neill, Darren P.; Zanville, Noah R.; Champion, Victoria L.; Schneider, Bryan P.

2016-01-01

Purpose To investigate the longitudinal relationship between chemotherapy-induced peripheral neuropathy (CIPN) symptoms (sx) and brain perfusion changes in patients with breast cancer. Interaction of CIPN-sx perfusion effects with known chemotherapy-associated gray matter density decrease was also assessed to elucidate the relationship between CIPN and previously reported cancer treatment–related brain structural changes. Methods Patients with breast cancer treated with (n = 24) or without (n = 23) chemotherapy underwent clinical examination and brain magnetic resonance imaging at the following three time points: before treatment (baseline), 1 month after treatment completion, and 1 year after the 1-month assessment. CIPN-sx were evaluated with the self-reported Functional Assessment of Cancer Therapy/Gynecologic Oncology Group–Neurotoxicity four-item sensory-specific scale. Perfusion and gray matter density were assessed using voxel-based pulsed arterial spin labeling and morphometric analyses and tested for association with CIPN-sx in the patients who received chemotherapy. Results Patients who received chemotherapy reported significantly increased CIPN-sx from baseline to 1 month, with partial recovery by 1 year (P < .001). CIPN-sx increase from baseline to 1 month was significantly greater for patients who received chemotherapy compared with those who did not (P = .001). At 1 month, neuroimaging showed that for the group that received chemotherapy, CIPN-sx were positively associated with cerebral perfusion in the right superior frontal gyrus and cingulate gyrus, regions associated with pain processing (P < .001). Longitudinal magnetic resonance imaging analysis in the group receiving chemotherapy indicated that CIPN-sx and associated perfusion changes from baseline to 1 month were also positively correlated with gray matter density change (P < .005). Conclusion Peripheral neuropathy symptoms after systemic chemotherapy for breast cancer are associated with changes in cerebral perfusion and gray matter. The specific mechanisms warrant further investigation given the potential diagnostic and therapeutic implications. PMID:26527786

Combination of blood flow asymmetry in the cerebral and cerebellar hemispheres on brain perfusion SPECT predicts 5-year outcome in patients with symptomatic unilateral major cerebral artery occlusion.

PubMed

Nomura, Jun-ichi; Ogasawara, Kuniaki; Saito, Hideo; Terasaki, Kazunori; Matsumoto, Yoshiyasu; Takahashi, Yoshihiro; Ogasawara, Yasushi; Saura, Hiroaki; Yoshida, Koji; Sato, Yuiko; Kubo, Yoshitaka; Ogawa, Akira

2014-03-01

Misery perfusion increases the risk of stroke recurrence in patients with symptomatic major cerebral artery occlusion. The ratio of brain perfusion contralateral-to-affected asymmetry in the cerebellar hemisphere to brain perfusion affected-to-contralateral asymmetry in the cerebral hemisphere (CblPR/CbrPR) indicates affected-to-contralateral asymmetry of oxygen extraction fraction (OEF) in the cerebral hemisphere. The purpose of the present study was to determine whether the CblPR/CbrPR on brain perfusion single-photon emission computed tomography (SPECT) predicts 5-year outcomes in patients with symptomatic unilateral occlusion of the middle cerebral artery (MCA) or internal carotid artery (ICA). Brain perfusion was assessed using N-isopropyl-p-[123I]-iodoamphetamine (123I-IMP) SPECT in 70 patients. A region of interest (ROI) was manually placed in the bilateral MCA territories and in the bilateral cerebellar hemispheres, and the CblPR/CbrPR was calculated. All patients were prospectively followed for 5 years. The primary end points were stroke recurrence or death. A total of 17 patients exhibited the primary end points, 11 of whom experienced subsequent ipsilateral strokes. Multivariate analysis revealed that only high CblPR/CbrPR was significantly associated with the development of the primary end point or subsequent ipsilateral strokes (95% confidential limits [CIs], 1.130-3.145; P  =  0.0114 or 95% CIs, 2.558-5.140; P  =  0.0045, respectively). The CblPR/CbrPR provided 65% (11/17) or 91% (10/11) sensitivity and 88% (47/53) or 88% (52/59) specificity in predicting the primary end point or subsequent ipsilateral strokes, respectively. The CblPR/CbrPR on brain perfusion SPECT predicts 5-year outcomes in patients with symptomatic unilateral occlusion of the MCA or ICA.

Contrast-Enhanced Ultrasound (CEUS) and Quantitative Perfusion Analysis in Patients with Suspicion for Prostate Cancer.

PubMed

Maxeiner, Andreas; Fischer, Thomas; Schwabe, Julia; Baur, Alexander Daniel Jacques; Stephan, Carsten; Peters, Robert; Slowinski, Torsten; von Laffert, Maximilian; Marticorena Garcia, Stephan Rodrigo; Hamm, Bernd; Jung, Ernst-Michael

2018-06-06

 The aim of this study was to investigate contrast-enhanced ultrasound (CEUS) parameters acquired by software during magnetic resonance imaging (MRI) US fusion-guided biopsy for prostate cancer (PCa) detection and discrimination.  From 2012 to 2015, 158 out of 165 men with suspicion for PCa and with at least 1 negative biopsy of the prostate were included and underwent a multi-parametric 3 Tesla MRI and an MRI/US fusion-guided biopsy, consecutively. CEUS was conducted during biopsy with intravenous bolus application of 2.4 mL of SonoVue ® (Bracco, Milan, Italy). In the latter CEUS clips were investigated using quantitative perfusion analysis software (VueBox, Bracco). The area of strongest enhancement within the MRI pre-located region was investigated and all available parameters from the quantification tool box were collected and analyzed for PCa and its further differentiation was based on the histopathological results.  The overall detection rate was 74 (47 %) PCa cases in 158 included patients. From these 74 PCa cases, 49 (66 %) were graded Gleason ≥ 3 + 4 = 7 (ISUP ≥ 2) PCa. The best results for cancer detection over all quantitative perfusion parameters were rise time (p = 0.026) and time to peak (p = 0.037). Within the subgroup analysis (> vs ≤ 3 + 4 = 7a (ISUP 2)), peak enhancement (p = 0.012), wash-in rate (p = 0.011), wash-out rate (p = 0.007) and wash-in perfusion index (p = 0.014) also showed statistical significance.  The quantification of CEUS parameters was able to discriminate PCa aggressiveness during MRI/US fusion-guided prostate biopsy. © Georg Thieme Verlag KG Stuttgart · New York.

Life-cycle and cost of goods assessment of fed-batch and perfusion-based manufacturing processes for mAbs.

PubMed

Bunnak, Phumthep; Allmendinger, Richard; Ramasamy, Sri V; Lettieri, Paola; Titchener-Hooker, Nigel J

2016-09-01

Life-cycle assessment (LCA) is an environmental assessment tool that quantifies the environmental impact associated with a product or a process (e.g., water consumption, energy requirements, and solid waste generation). While LCA is a standard approach in many commercial industries, its application has not been exploited widely in the bioprocessing sector. To contribute toward the design of more cost-efficient, robust and environmentally-friendly manufacturing process for monoclonal antibodies (mAbs), a framework consisting of an LCA and economic analysis combined with a sensitivity analysis of manufacturing process parameters and a production scale-up study is presented. The efficiency of the framework is demonstrated using a comparative study of the two most commonly used upstream configurations for mAb manufacture, namely fed-batch (FB) and perfusion-based processes. Results obtained by the framework are presented using a range of visualization tools, and indicate that a standard perfusion process (with a pooling duration of 4 days) has similar cost of goods than a FB process but a larger environmental footprint because it consumed 35% more water, demanded 17% more energy, and emitted 17% more CO 2 than the FB process. Water consumption was the most important impact category, especially when scaling-up the processes, as energy was required to produce process water and water-for-injection, while CO 2 was emitted from energy generation. The sensitivity analysis revealed that the perfusion process can be made more environmentally-friendly than the FB process if the pooling duration is extended to 8 days. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1324-1335, 2016. © 2016 The Authors Biotechnology Progress published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers.

Effect of Ranolazine on Left Ventricular Dyssynchrony in Patients with Coronary Artery Disease

PubMed Central

Venkataraman, Rajesh; Chen, Ji; Garcia, Ernest V.; Belardinelli, Luiz; Hage, Fadi G.; Heo, Jaekyeong; Iskandrian, Ami E.

2012-01-01

We previously reported that ranolazine improved exercise myocardial perfusion. Ranolazine ameliorates myocardial ischemia by augmenting myocardial blood flow; likely due to a reduction in extra-vascular compression of small vessels. We hypothesized that ranolazine could improve left ventricular (LV) dyssynchrony as assessed by phase analysis of gated SPECT myocardial perfusion imaging (MPI). Patients (n=32) with known or suspected coronary artery disease and reversible perfusion defects on a clinically indicated stress MPI were re-studied 4 weeks after ranolazine (500–1000 mg orally twice daily) was added to their conventional treatment in an open-label trial (data previously reported). The LV systolic and diastolic dyssynchrony indices were obtained using automated phase analysis before and after ranolazine. There were no significant changes in heart rate and blood pressure (at rest or during stress) after treatment. The perfusion pattern improved in 13 of 18 patients who had exercise testing but in only 3 of 14 patients who had vasodilator stress testing. There were no significant changes in LV ejection fraction or volumes after treatment. The systolic and diastolic LV dyssynchrony improved after ranolazine therapy; there was a significant decrease in systolic phase standard deviation (SD) (21±17 vs. 18±13, P=0.04), systolic bandwidth (BW) (69±60 vs. 53±38, P=0.03), diastolic SD (29±18 vs. 24±15, P=0.047) and diastolic BW (91±61 vs. 72±45, P=0.02). In conclusion, this is the first study to show improvement in diastolic and systolic LV synchrony with ranolazine as measured by automated phase analysis of gated SPECT MPI. PMID:22884560

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

PubMed

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

2016-10-01

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

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

PubMed Central

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

2016-01-01

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

Usefulness of myocardial parametric imaging to evaluate myocardial viability in experimental and in clinical studies.

PubMed

Korosoglou, G; Hansen, A; Bekeredjian, R; Filusch, A; Hardt, S; Wolf, D; Schellberg, D; Katus, H A; Kuecherer, H

2006-03-01

To evaluate whether myocardial parametric imaging (MPI) is superior to visual assessment for the evaluation of myocardial viability. Myocardial contrast echocardiography (MCE) was assessed in 11 pigs before, during, and after left anterior descending coronary artery occlusion and in 32 patients with ischaemic heart disease by using intravenous SonoVue administration. In experimental studies perfusion defect area assessment by MPI was compared with visually guided perfusion defect planimetry. Histological assessment of necrotic tissue was the standard reference. In clinical studies viability was assessed on a segmental level by (1) visual analysis of myocardial opacification; (2) quantitative estimation of myocardial blood flow in regions of interest; and (3) MPI. Functional recovery between three and six months after revascularisation was the standard reference. In experimental studies, compared with visually guided perfusion defect planimetry, planimetric assessment of infarct size by MPI correlated more significantly with histology (r2 = 0.92 versus r2 = 0.56) and had a lower intraobserver variability (4% v 15%, p < 0.05). In clinical studies, MPI had higher specificity (66% v 43%, p < 0.05) than visual MCE and good accuracy (81%) for viability detection. It was less time consuming (3.4 (1.6) v 9.2 (2.4) minutes per image, p < 0.05) than quantitative blood flow estimation by regions of interest and increased the agreement between observers interpreting myocardial perfusion (kappa = 0.87 v kappa = 0.75, p < 0.05). MPI is useful for the evaluation of myocardial viability both in animals and in patients. It is less time consuming than quantification analysis by regions of interest and less observer dependent than visual analysis. Thus, strategies incorporating this technique may be valuable for the evaluation of myocardial viability in clinical routine.

Classification of arterial and venous cerebral vasculature based on wavelet postprocessing of CT perfusion data.

PubMed

Havla, Lukas; Schneider, Moritz J; Thierfelder, Kolja M; Beyer, Sebastian E; Ertl-Wagner, Birgit; Reiser, Maximilian F; Sommer, Wieland H; Dietrich, Olaf

2016-02-01

The purpose of this study was to propose and evaluate a new wavelet-based technique for classification of arterial and venous vessels using time-resolved cerebral CT perfusion data sets. Fourteen consecutive patients (mean age 73 yr, range 17-97) with suspected stroke but no pathology in follow-up MRI were included. A CT perfusion scan with 32 dynamic phases was performed during intravenous bolus contrast-agent application. After rigid-body motion correction, a Paul wavelet (order 1) was used to calculate voxelwise the wavelet power spectrum (WPS) of each attenuation-time course. The angiographic intensity A was defined as the maximum of the WPS, located at the coordinates T (time axis) and W (scale/width axis) within the WPS. Using these three parameters (A, T, W) separately as well as combined by (1) Fisher's linear discriminant analysis (FLDA), (2) logistic regression (LogR) analysis, or (3) support vector machine (SVM) analysis, their potential to classify 18 different arterial and venous vessel segments per subject was evaluated. The best vessel classification was obtained using all three parameters A and T and W [area under the curve (AUC): 0.953 with FLDA and 0.957 with LogR or SVM]. In direct comparison, the wavelet-derived parameters provided performance at least equal to conventional attenuation-time-course parameters. The maximum AUC obtained from the proposed wavelet parameters was slightly (although not statistically significantly) higher than the maximum AUC (0.945) obtained from the conventional parameters. A new method to classify arterial and venous cerebral vessels with high statistical accuracy was introduced based on the time-domain wavelet transform of dynamic CT perfusion data in combination with linear or nonlinear multidimensional classification techniques.

Microdialysis of Soil P: A means to mimic root uptake?

NASA Astrophysics Data System (ADS)

Schack-Kirschner, Helmer; Demand, Dominic; Lang, Friederike

2017-04-01

Standard procedures to assess P availability in soils are based on batch experiments with various extractants. However, in most soils P nutrition is less limited by bulk stocks but by slow diffusion of phosphate through the soil solution. More comparable to the root's approach is to strip phosphate locally from the solid phase by lowering the soil-solution concentration, which can be achieved by establishing an infinite diffusional sink, such as DGT. An alternative diffusive sampling technique is microdialysis (MD), well established in pharmacokinetics. Briefly, this method uses miniaturized flow-through probes where the perfusate gets in diffusive contact to the external solution by a semipermeable membrane. Important aspects of P supply to roots resemble MD sampling. This is not only the mostly diffusive transport, but also an elongated capillary tube-like geometry of absorption. The diameter of typical commercial MD probes is around 500μm. One additional inherent feature of microdialysis is the possibility to release low-molecular substances from the perfusate by diffusion into the matrix, such as carboxylates. However, microdialysis has yet not been used for P in soils. We tested microdialysis in topsoils of an acid beech forest, of an unfertilized grassland and of a fertilized crop site. Three perfusates have been used: 1 mM KNO3, electrolyte + 0.1 mM citric acid, and electrolyte + 1 mM citric acid. We observed rates of uptake into the probes in a range between 1.5*10-15 and 6.7*10-14 mol s-1cm-1 in case of no citrate addition. Surprisingly, these uptake rates were mostly independent of the bulk stocks. Citrate addition increased P yields only in the higher concentration but not in the forest soil. The order of magnitude of MD uptake rates from the soil samples matched root-length related uptake rates from other studies. The micro-radial citrate release in MD reflects the processes controlling phosphate mobilization in the rhizosphere better than measurements based on "flooding" of soil samples with citric acid in batch experiments. Important challenges in MD with phosphate are small volumes of dialysate with extremely low concentrations and a high variability of results due to soil heterogeneity and between-probe variability. We conclude that MD is a promising tool to complement existing P-analytical procedures, especially when spatial aspects or the release of mobilizing substances are in focus.

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.

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 lower scaffolds. Our methodology can be extended to other cell types to investigate the influence of 3D culture conditions on the expression of other relevant cell markers.

Critical Ischemia Times and the Effect of Novel Preservation Solutions HTK-N and TiProtec on Tissues of a Vascularized Tissue Isograft.

PubMed

Messner, Franka; Hautz, Theresa; Blumer, Michael J F; Bitsche, Mario; Pechriggl, Elisabeth J; Hermann, Martin; Zelger, Bettina; Zelger, Bernhard; Öfner, Dietmar; Schneeberger, Stefan

2017-09-01

We herein investigate critical ischemia times and the effect of novel preservation solutions such as new histidine-tryptophan-ketoglutarate (HTK-N) and TiProtec on the individual tissues of a rat limb isograft. Orthotopic hind-limb transplantations were performed in male Lewis rats after 2 hours, 6 hours, or 10 hours of cold ischemia (CI). Limbs were flushed and stored in HTK-N, TiProtec, HTK, or saline solution. Muscle, nerve, vessel, skin, and bone samples were procured on day 10 for histology, immunohistochemistry, confocal and electron microscopy, and quantitative real-time polymerase chain reaction analysis. Histomorphology of the muscle showed a mainly perivascular inflammatory infiltrate, fibrotic degeneration, and neovascularization after 6 hours and 10 hours of CI. However, centrally aligned nuclei observed in muscle fibers suggest for muscle regeneration in these samples. In addition to Wallerian degeneration, nerve injury was significantly aggravated (P = 0.032) after prolonged CI. Proinflammatory and regulatory cytokines were most significantly upregulated after 2-hour CI. Our data suggest no superiority of novel perfusates HTK-N and TiProtec in terms of tissue preservation, compared with HTK and saline. Limiting CI time for less than 6 hours is the most significant factor to reduce tissue damage in vascularized tissue transplantation. Signs of muscle regeneration give rise that ischemic muscle damage in limb transplantation might be reversible to a certain extent.

Intra-arterial nitroglycerin for intra-operative arterial vasospasm during pediatric renal transplantation.

PubMed

Penna, Frank J; Harvey, Elizabeth; John, Philip; Armstrong, Derek; Luginbuehl, Igor; Odeh, Rakan I; Alyami, Fahad; Koyle, Martin A; Lorenzo, Armando J

2016-05-01

Intra-operative arterial vasospasm during pediatric renal transplantation is an urgent clinical situation resulting in end-organ ischemia, associated changes in parenchymal turgor and color, diminished flow on ultrasound, and if left untreated, allograft loss. We hypothesized that intra-operative intra-arterial injection of nitroglycerin would reverse vasospasm and improve renal perfusion. A three-yr-old girl with end-stage renal disease due to autosomal recessive polycystic kidney disease on peritoneal dialysis underwent deceased donor renal transplantation. After optimal immediate reperfusion and hemodynamic parameters, the kidney lost turgor and became mottled in appearance despite adequate hilar arterial and venous Doppler waveforms. Two aliquots of 40 μg (0.4 mL of a 100 μg/mL) nitroglycerin solution were injected directly into the renal artery 10 min apart. Nitroglycerin resulted in dramatic change in the consistency and appearance of the allograft. An improvement in renal blood flow was demonstrated by ultrasound after the second intra-arterial nitroglycerin injection with only a transient decrease in systemic arterial blood pressure. The child experienced normal allograft perfusion on serial postoperative ultrasounds, with a prompt decrease in serum creatinine and excellent diuresis. Intra-arterial nitroglycerin is a promising option for intra-operative arterial vasospasm during pediatric renal transplantation with objective improvement in blood flow and perfusion. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Air elimination capability in rapid infusion systems.

PubMed

Zoremba, N; Gruenewald, C; Zoremba, M; Rossaint, R; Schaelte, G

2011-11-01

Pressure infusion devices are used in clinical practice to apply large volumes of fluid over a short period of time. Although air infusion is a major complication, they have limited capability to detect and remove air during pressure infusion. In this investigation, we tested the air elimination capabilities of the Fluido(®) (The Surgical Company), Level 1(®) (Level 1 Technologies Inc.) and Ranger(®) (Augustine Medical GmbH) pressure infusion devices. Measurements were undertaken with a crystalloid solution during an infusion flow of 100, 200, 400 and 800 ml.min(-1). Four different volumes of air (25, 50, 100 and 200 ml) were injected as boluses in one experimental setting, or infused continuously over the time needed to perfuse 2 l saline in the other setting. The perfusion fluid was collected in an airtight infusion bag and the amount of air obtained in the bag was measured. The delivered air volume was negligible and would not cause any significant air embolism in all experiments. In our experimental setting, we found, during high flow, an increased amount of uneliminated air in all used devices compared with lower perfusion flows. All tested devices had a good air elimination capability. The use of ultrasonic air detection coupled with an automatic shutoff is a significant safety improvement and can reliably prevent accidental air embolism at rapid flows. © 2011 The Authors. Anaesthesia © 2011 The Association of Anaesthetists of Great Britain and Ireland.

Investigation of optimal acquisition time of myocardial perfusion scintigraphy using cardiac focusing-collimator

NASA Astrophysics Data System (ADS)

Niwa, Arisa; Abe, Shinji; Fujita, Naotoshi; Kono, Hidetaka; Odagawa, Tetsuro; Fujita, Yusuke; Tsuchiya, Saki; Kato, Katsuhiko

2015-03-01

Recently myocardial perfusion SPECT imaging acquired using the cardiac focusing-collimator (CF) has been developed in the field of nuclear cardiology. Previously we have investigated the basic characteristics of CF using physical phantoms. This study was aimed at determining the acquisition time for CF that enables to acquire the SPECT images equivalent to those acquired by the conventional method in 201TlCl myocardial perfusion SPECT. In this study, Siemens Symbia T6 was used by setting the torso phantom equipped with the cardiac, pulmonary, and hepatic components. 201TlCl solution were filled in the left ventricular (LV) myocardium and liver. Each of CF, the low energy high resolution collimator (LEHR), and the low medium energy general purpose collimator (LMEGP) was set on the SPECT equipment. Data acquisitions were made by regarding the center of the phantom as the center of the heart in CF at various acquisition times. Acquired data were reconstructed, and the polar maps were created from the reconstructed images. Coefficient of variation (CV) was calculated as the mean counts determined on the polar maps with their standard deviations. When CF was used, CV was lower at longer acquisition times. CV calculated from the polar maps acquired using CF at 2.83 min of acquisition time was equivalent to CV calculated from those acquired using LEHR in a 180°acquisition range at 20 min of acquisition time.

Extracellular cyclic AMP-adenosine pathway in isolated adipocytes and adipose tissue.

PubMed

Strouch, Marci B; Jackson, Edwin K; Mi, Zaichuan; Metes, Nicole A; Carey, Gale B

2005-06-01

Our goal was to evaluate the presence and lipolytic impact of the extracellular cyclic adenosine monophosphate (AMP)-adenosine pathway in adipose tissue. Sixteen miniature Yucatan swine (Sus scrofa) were used for these in vitro and in situ experiments. Four microdialysis probes were implanted into subcutaneous adipose tissue and perfused at 2 microL/min with Ringer's solution containing no addition, varying levels of cyclic AMP, 10 microM isoproterenol, or 10 microM isoproterenol plus 1 mM alpha,beta-methylene adenosine 5'-diphosphate (AMPCP), a 5'-nucleotidase inhibitor. Dialysate was assayed for AMP, adenosine, inosine, hypoxanthine, and glycerol. Freshly isolated adipocytes were incubated with buffer, 1 microM isoproterenol, or 1 microM isoproterenol plus 0.1 mM AMPCP, and extracellular levels of AMP, adenosine, inosine, hypoxanthine, and glycerol were measured. Perfusion of adipose tissue with exogenous cyclic AMP caused a significant increase in AMP and adenosine appearance. Perfusion with AMPCP, in the presence or absence of isoproterenol, significantly increased the levels of AMP and glycerol, whereas it significantly reduced the level of adenosine and its metabolites. However, the AMPCP-provoked increase in lipolysis observed in situ and in vitro was not temporally associated with a decrease in adenosine. These data suggest the existence of a cyclic AMP-adenosine pathway in adipocytes and adipose tissue. The role of this pathway in the regulation of lipolysis remains to be clarified.

Flexible reduced field of view magnetic resonance imaging based on single-shot spatiotemporally encoded technique

NASA Astrophysics Data System (ADS)

Li, Jing; Cai, Cong-Bo; Chen, Lin; Chen, Ying; Qu, Xiao-Bo; Cai, Shu-Hui

2015-10-01

In many ultrafast imaging applications, the reduced field-of-view (rFOV) technique is often used to enhance the spatial resolution and field inhomogeneity immunity of the images. The stationary-phase characteristic of the spatiotemporally-encoded (SPEN) method offers an inherent applicability to rFOV imaging. In this study, a flexible rFOV imaging method is presented and the superiority of the SPEN approach in rFOV imaging is demonstrated. The proposed method is validated with phantom and in vivo rat experiments, including cardiac imaging and contrast-enhanced perfusion imaging. For comparison, the echo planar imaging (EPI) experiments with orthogonal RF excitation are also performed. The results show that the signal-to-noise ratios of the images acquired by the proposed method can be higher than those obtained with the rFOV EPI. Moreover, the proposed method shows better performance in the cardiac imaging and perfusion imaging of rat kidney, and it can scan one or more regions of interest (ROIs) with high spatial resolution in a single shot. It might be a favorable solution to ultrafast imaging applications in cases with severe susceptibility heterogeneities, such as cardiac imaging and perfusion imaging. Furthermore, it might be promising in applications with separate ROIs, such as mammary and limb imaging. Project supported by the National Natural Science Foundation of China (Grant Nos. 11474236, 81171331, and U1232212).

Effect of azelastine on sulphur dioxide induced impairment of ciliary motility in airway epithelium.

PubMed Central

Tamaoki, J; Chiyotani, A; Sakai, N; Takeyama, K; Konno, K

1993-01-01

OBJECTIVE--The effect of azelastine on airway mucociliary transport function was studied by measuring ciliary motility of human bronchial epithelium in vitro with a photoelectric method. METHOD--Bronchial epithelial cells were obtained by fibreoptic bronchoscopy, mounted in a Rose chamber, and perfused with Krebs-Henseleit solution. The preparations were placed on a microscope stage equipped with an illuminator, and the variations of light intensity caused by ciliary beating were detected by a photometer. RESULTS--The addition of azelastine to the perfusate increased ciliary beat frequency (CBF) in a dose dependent manner without ciliary discoordination. The mean (SE) maximal increase from the baseline value and the concentration required to produce a half maximal effect were 27.0 (4.2)% and 9.2 x 10(-6) mol/l, respectively. Exposure of the cells to the perfusate containing 3 ppm sulphur dioxide rapidly decreased CBF by 59.2 (5.0)%, and was accompanied by a reduction in intracellular cyclic AMP levels from 38.1 (4.3) to 10.1 (2.4) pmol/mg protein. This effect was prevented by pretreatment of cells with azelastine in a dose dependent manner. CONCLUSIONS--Azelastine not only stimulates ciliary motility of airway epithelium and hence mucociliary transport function, but may also protect against sulphur dioxide induced ciliary dysfunction, probably by inhibiting intracellular cyclic AMP loss. PMID:8322244

Aortoiliac aneurysm with congenital right pelvic kidney.

PubMed

Date, Kazuma; Okada, Shuuichi; Ezure, Masahiko; Takihara, Hitomi; Okonogi, Shuuichi; Hasegawa, Yutaka; Sato, Yasushi; Kaneko, Tatsuo

2015-05-01

The association of congenital pelvic kidney with abdominal aortoiliac aneurysm is an extremely rare clinical finding. Previous reports have described various methods of aneurysm repair with successful preservation of the function of pelvic kidney. However, to our knowledge, reconstruction of more than two renal arteries has not been established. We report a case of abdominal aortic aneurysm complicated by congenital right pelvic kidney in a 72-year-old man. Computed tomography (CT) revealed an abdominal aortic aneurysm with a maximum diameter of 54 mm and a right common iliac aneurysm of 45 mm. In addition, he had a congenital right pelvic kidney and CT angiography identified three right pelvic renal arteries. The upper artery originated from the bifurcation of the terminal aorta and the lower two originated from the right common iliac artery. Three-dimensional CT was helpful for the accurate planning of the operation. Open surgical repair of the aortoiliac aneurysm with a Dacron bifurcated graft replacement was decided and reimplantation of all three right pelvic kidney arteries to the right limb of the graft was also performed. For renal preservation, the right pelvic kidney arteries were perfused with cold Ringer's lactate using a rapid infusion pump and coronary perfusion cannula. The patient's postoperative course was uneventful, and worsening of renal function was not observed. The perfusion of renal arteries with cold Ringer's solution was thought to be a simple and appropriate procedure for renal protection.

Effect of alpha-adrenoceptor antagonists (phentolamine, nicergoline and prazosin) on reperfusion arrhythmias and noradrenaline release in perfused rat heart.

PubMed Central

Bralet, J.; Didier, J.; Moreau, D.; Opie, L. H.; Rochette, L.

1985-01-01

Rat isolated hearts were perfused through the left atrium with a modified Krebs-Henseleit solution or mounted on a Langendorff perfusion system. The hearts were prelabelled with [3H]-noradrenaline [( 3H]-NA) and the left main coronary artery was ligated for 10 min after which reperfusion followed. The liberation of [3H]-NA and the development of ventricular tachycardia and fibrillation were monitored throughout. During the occlusion period, ventricular arrhythmias did not occur and heart rate was not significantly altered in the control series. In contrast, reperfusion was followed by ventricular fibrillation and ventricular tachycardia in all the hearts in the control series (Langendorff or 'working' models). The alpha-adrenoceptor antagonists phentolamine (7.1 X 10(-6) M and 7.1 X 10(-5) M) and nicergoline (3.1 X 10(-6) M) diminished or prevented reperfusion arrhythmias. However, prazosin (5.2 X 10(-6) M) was not effective. The lower concentration of phentolamine did not alter the pattern of [3H]-NA release, whereas, high doses of phentolamine and nicergoline increased the release of [3H]-NA. Prazosin (5.2 X 10(-6) M) caused a very marked increase in release of [3H]-NA but was not antiarrhythmic. A 'membrane-stabilizing' effect seems the most appropriate explanation for these antiarrhythmic effects of alpha-antagonist agents. PMID:2858234

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

PubMed

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

2017-06-28

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