Stemphylium revisited.

In 2007 a new Stemphylium leaf spot disease of Beta vulgaris (sugar beet) spread through the Netherlands. Attempts to identify this destructive Stemphylium sp. in sugar beet led to a phylogenetic revision of the genus. The name Stemphylium has been recommended for use over that of its sexual morph, Pleospora, which is polyphyletic. Stemphylium forms a well-defined monophyletic genus in the Pleosporaceae, Pleosporales (Dothideomycetes), but lacks an up-to-date phylogeny. To address this issue, the internal transcribed spacer 1 and 2 and intervening 5.8S nr DNA (ITS) of all available Stemphylium and Pleospora isolates from the CBS culture collection of the Westerdijk Institute (N = 418), and from 23 freshly collected isolates obtained from sugar beet and related hosts, were sequenced to construct an overview phylogeny (N = 350). Based on their phylogenetic informativeness, parts of the protein-coding genes calmodulin and glyceraldehyde-3-phosphate dehydrogenase were also sequenced for a subset of isolates (N = 149). This resulted in a multi-gene phylogeny of the genus Stemphylium containing 28 species-clades, of which five were found to represent new species. The majority of the sugar beet isolates, including isolates from the Netherlands, Germany and the UK, clustered together in a species clade for which the name S. beticola was recently proposed. Morphological studies were performed to describe the new species. Twenty-two names were reduced to synonymy, and two new combinations proposed. Three epitypes, one lectotype and two neotypes were also designated in order to create a uniform taxonomy for Stemphylium.

Modelling of temperature and perfusion during scalp cooling.

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

Monitoring of deep brain temperature in infants using multi-frequency microwave radiometry and thermal modelling.

In this study we present a design for a multi-frequency microwave radiometer aimed at prolonged monitoring of deep brain temperature in newborn infants and suitable for use during hypothermic neural rescue therapy. We identify appropriate hardware to measure brightness temperature and evaluate the accuracy of the measurements. We describe a method to estimate the tissue temperature distribution from measured brightness temperatures which uses the results of numerical simulations of the tissue temperature as well as the propagation of the microwaves in a realistic detailed three-dimensional infant head model. The temperature retrieval method is then used to evaluate how the statistical fluctuations in the measured brightness temperatures limit the confidence interval for the estimated temperature: for an 18 degrees C temperature differential between cooled surface and deep brain we found a standard error in the estimated central brain temperature of 0.75 degrees C. Evaluation of the systematic errors arising from inaccuracies in model parameters showed that realistic deviations in tissue parameters have little impact compared to uncertainty in the thickness of the bolus between the receiving antenna and the infant's head or in the skull thickness. This highlights the need to pay particular attention to these latter parameters in future practical implementation of the technique.

Numerical modeling of temperature distributions within the neonatal head.

Introduction of hypothermia therapy as a neuroprotection therapy after hypoxia-ischemia in newborn infants requires appraisal of cooling methods. In this numerical study thermal simulations were performed to test the hypothesis that cooling of the surface of the cranium by the application of a cooling bonnet significantly reduces deep brain temperature and produces a temperature differential between the deep brain and the body core. A realistic three-dimensional (3-D) computer model of infant head anatomy was used, derived from magnetic resonance data from a newborn infant. Temperature distributions were calculated using the Pennes heatsink model. The cooling bonnet was at a constant temperature of 10 degrees C. When modeling head cooling only, a constant body core temperature of 37 degrees C was imposed. The computed result showed no significant cooling of the deep brain regions, only the very superficial regions of the brain are cooled to temperatures of 33-34 degrees C. Poor efficacy of head cooling was still found after a considerable increase in the modeled thermal conductivities of the skin and skull, or after a decrease in perfusion. The results for the heatsink thermal model of the infant head were confirmed by comparison of results computed for a scaled down adult head, using both the heatsink description and a discrete vessel thermal model with both anatomy and vasculature obtained from MR data. The results indicate that significant reduction in brain temperature will only be achieved if the infant's core temperature is lowered.

Temperature simulations in tissue with a realistic computer generated vessel network.

The practical use of a discrete vessel thermal model for hyperthermia treatment planning requires a number of choices with respect to the unknown part of the patient's vasculature. This work presents a study of the thermal effects of blood flow in a simple tissue geometry with a detailed artificial vessel network. The simulations presented here demonstrate that an incomplete discrete description of the detailed network results in a better prediction of the temperature distribution than is obtained using the conventional bio-heatsink equation. Therefore, efforts to obtain information on the positions of the large vessels in an individual hyperthermia patient will be rewarded with a more accurate prediction of the temperature distribution.

Calculation of change in brain temperatures due to exposure to a mobile phone.

In this study we evaluated for a realistic head model the 3D temperature rise induced by a mobile phone. This was done numerically with the consecutive use of an FDTD model to predict the absorbed electromagnetic power distribution, and a thermal model describing bioheat transfer both by conduction and by blood flow. We calculated a maximum rise in brain temperature of 0.11 degrees C for an antenna with an average emitted power of 0.25 W, the maximum value in common mobile phones, and indefinite exposure. Maximum temperature rise is at the skin. The power distributions were characterized by a maximum averaged SAR over an arbitrarily shaped 10 g volume of approximately 1.6 W kg(-1). Although these power distributions are not in compliance with all proposed safety standards, temperature rises are far too small to have lasting effects. We verified our simulations by measuring the skin temperature rise experimentally. Our simulation method can be instrumental in further development of safety standards.

Modelling the thermal impact of a discrete vessel tree.

Based on a modelling technique to calculate the thermal influence of a single vessel segment, a combination of segments representing a vessel tree is presented. At segment junctions the blood temperature is passed with a correction for a single vessel artefact. Blood leaving the modelled arterial vessel network at a junction or at the end of a terminal branch need not be equilibrated with the local surrounding tissue temperature. The thermal effect of this equilibration process can be taken into account using the 'sink set'. Blood entering a venous vessel tree is given an inflow temperature based on the tissue temperatures in the 'sample set'. With these sets we model the thermal impact of the vasculature too small to be taken into account discretely. The formation of the sink/sample sets is subject of current research; to show the capabilities of the presented method we present a minimal simulation collection with cube-shaped sets in combination with limited vasculature. The results of using the entire simulation volume as sink and sample sets for all the terminal branches matches the reference temperature profile best.

A flexible algorithm for construction of 3-D vessel networks for use in thermal modeling.

A new algorithm for the construction of artificial blood vessel networks is presented. The algorithm produces three-dimensional (3-D) geometrical representations of both arterial and venous networks. The key ingredient of the algorithm is a 3-D potential function defined in the tissue volume. This potential function controls the paths by which points are connected to existing vessels, thereby producing new vessel segments. The potential function has no physiological interpretation, but, by adjustment of parameters governing the potential, it is possible to produce networks that have physiologically meaningful geometrical properties. If desired, the veins can be generated counter current to the arteries. Furthermore, the potential function allows fashioning of the networks to the presence of bone or air cavities. The resulting networks can be used for thermal simulations of hyperthermia treatment.

Dose uniformity of ferromagnetic seed implants in tissue with discrete vasculature: a numerical study on the impact of seed characteristics and implantation techniques.

The results from simulations with a new three-dimensional treatment planning system for interstitial hyperthermia with ferromagnetic seeds are presented in this study. The thermal model incorporates discrete vessel structures as well as a heat sink and enhanced thermal conductivity. Both the discrete vessels and the ferroseeds are described parametrically in separate calculation spaces. This parametric description has the advantage of an arbitrary orientation of the structures within the tissue grid, easy manipulation of the structures and independence from the resolution of the tissue voxels (tissue calculation space). The power absorption of the self-regulating seeds is according to empirical data. The thermal effects of an unlimited number of thin layers surrounding the seed (coatings, catheters) can be modelled. The initial calculations have been performed for an array of 12 identical ferromagnetic seeds in a tissue volume with a computer generated artificial vessel network spanning four vessel generations in both the arterial and venous tree. The heterogeneously distributed large isolated vessels impair the temperature distribution significantly, indicating the limited accuracy of continuum models. Simulations with different types of ferromagnetic seeds have confirmed that the efforts of previous studies to optimize the self-regulating temperature control and the implantation techniques of the ferroseeds will improve the homogeneity of the temperature distribution in the target volume. Multifilament seeds implanted in brachytherapy needles and tubular seeds appear to be the most favourable configurations. The division of long seeds into shorter segments with the appropriate Curie temperature will further improve the homogeneity of the temperature distribution without increasing the average temperature in the volume of interest. Given the proper thermal tissue data, the model presented in this study will prove to be a useful tool in making choices for the implant geometry, seed spacing and Curie temperature.

Tests of the geometrical description of blood vessels in a thermal model using counter-current geometries.

We have developed a thermal model, for use in hyperthermia treatment planning, in which blood vessels are described as geometrical objects; 3D curves with associated diameters. For the calculation of the heat exchange with the tissue an analytic result is used. To arrive at this result some assumptions were made. One of these assumptions is a cylindrically symmetric temperature distribution. In this paper the behaviour of the model is examined for counter-current vessel geometries for which this assumption is not valid. Counter-current vessel pairs intersecting a circular tissue slice are tested. For these 2D geometries vessel spacing, tissue radius and resolution are varied, as well as the position of the vessel pair with respect to the discretized tissue grid. The simulation results are evaluated by comparison of the different heat flow rates with analytical predictions. The tests show that for a fixed vessel configuration the accuracy is not a simple decreasing function of the voxel dimensions, but is also sensitive to the position of the configuration with respect to the discretized tissue grid.

The influence of vasculature on temperature distributions in MECS interstitial hyperthermia: importance of longitudinal control.

The quality of temperature distributions that can be generated with the Multi Electrode Current Source (MECS) interstitial hyperthermia (IHT) system, which allows 3D control of the temperature distribution, has been investigated. For the investigations, computer models of idealised anatomies containing discrete vessels, were used. A 7-catheter hexagonal implant geometry with a nearest neighbour distance of 15 mm was used. In each interstitial catheter with a diameter of 2.1 mm a number of 1 up to 4 electrodes were placed along an 'active section' with a length of 50 mm. The electrode segments had lengths of 50, 20, 12 and 9 mm respectively. Both single vessel and vessel network situations were analysed. This study shows that even in situations with discrete vasculature and perfusion heterogeneity it remains possible to obtain satisfactory temperature distributions with the MECS IHT system. Due to its 3D spatial control the temperature homogeneity in the implant can be made quite satisfactory.

Accuracy of geometrical modelling of heat transfer from tissue to blood vessels.

We have developed a thermal model in which blood vessels are described as geometrical objects, 3D curves with associated diameters. Here the behaviour of the model is examined for low resolutions compared with the vessel diameter and for strongly curved vessels. The tests include a single straight vessel and vessels describing the path of a helix embedded in square tissue blocks. The tests show the excellent behaviour of our discrete vessel implementation.

A description of discrete vessel segments in thermal modelling of tissues.

In hyperthermia treatment planning vessels with a diameter larger than 0.5 mm must be treated individually. Such vessels can be described as 3D curves with associated diameters. The temperature profile along the vessel is discretized one dimensionally. Separately the tissue is discretized three dimensionally on a regular grid of voxels. The vessel as well as the tissue are positioned in one global space. Methods are supplied to describe the tissue-vessel interaction, the shift of the blood temperature profile describing the flow of blood along the vessel and the calculation of the vessel wall temperature. The calculation of the interaction is based on tissue temperature samples and the blood temperature together with the distance between the centre of the vessel and the tissue temperature sample. An analytical expression for a vessel inside a coaxial tissue cylinder is then used for the calculation of the heat flow rate across the vessel wall. The basic test system is a vessel segment embedded inside a coaxial tissue cylinder. All the tests use this setup while the following simulation parameters are varied: position and orientation of the vessel relative to the tissue grid, vessel radius, sample density of the blood temperature and power deposition inside the tissue cylinder. The blood temperature profile is examined by calculation of the local estimate of the equilibration length. All tests show excellent agreement with the theory.

Dose uniformity in MECS interstitial hyperthermia: the impact of longitudinal control in model anatomies.

The quality of temperature distributions that can be generated with the multi-electrode current source (MECS) interstitial hyperthermia system, which allows 3D control of the spatial SAR distribution, has been investigated. For the investigations, computer models of idealized anatomies were used. These anatomical models did not contain discrete vessels. Binary-media anatomies, containing media interfaces oriented parallel, perpendicular or oblique with respect to the long axis of the implant, represent simple anatomies which can be encountered in the clinic. The implant volume was about 40 cm3. A seven-catheter hexagonal implant geometry with a nearest-neighbor distance of 15 mm was used. In each interstitial probe between one and four electrodes with a diameter of 2.1 mm were placed along an "active section' with a length of 50 mm. The electrode segments had lengths of 50, 20, 12 and 9 mm. This study shows that even with high contrasts in electrical and thermal conductivity in the implant it remains possible to obtain satisfactory temperature distributions with the MECS system. Due to its 3D spatial control the temperature homogeneity in the implant can be made quite satisfactory, with T10-T90 of the order of 2-3 K. Treatment planning must ensure that the placement of the current source electrodes is compatible with the media configuration.

Influence of high and low plasma insulin levels on the uptake of fluorine-18 fluorodeoxyglucose in myocardium and femoral muscle, assessed by planar imaging.

The aim of this study was to optimize the metabolic conditions for planar myocardial fluorine-18 fluorodeoxyglucose (FDG) imaging. The effects of high and low insulin levels during euglycaemic clamping on myocardial and femoral muscle FDG uptake were compared since insulin plays a major role in glucose metabolism. FDG uptake in 11 patients was studied using planar scintigraphy. Patients were studied twice: in the low-dose insulin protocol (LDI), insulin was infused at a rate of 20 mU/kg per hour, starting 1 h before FDG administration, while in the high-dose insulin protocol (HDI) it was infused at a rate of 100 mU/kg per hour. Glucose infusion rate was adjusted according to frequently determined blood glucose levels. Somatostatin was infused to block endogenous insulin release. Planar images were obtained from the thorax region and femoral muscles. Regions of interest were drawn over normal and abnormal myocardial areas (based on angiographic and thallium-201 data) and over lung, liver and muscle areas. After clamping, insulin levels during LDI and HDI at t = 60 were 30.6 +/- 13.3 and 129.6 +/- 30.5 mU/l respectively (P < 0.0001). Femoral muscle uptake was significantly higher during HDI (P < 0.001). Uptake in normal and abnormal myocardial areas did not differ between the two protocols. Heart/lung ratios (NS) and heart/liver ratios (P < 0.05) increased during HDI. It may be concluded that planar FDG imaging is influenced by plasma insulin levels. The euglycaemic hyperinsulinaemic clamp technique, although more demanding, gives an adjustable metabolic steady state without significantly altering the FDG uptake patterns in normal and abnormal myocardial regions. The image quality of planar FDG images improves due to lower background uptake of FDG during clamping with high plasma insulin levels.

Feasibility of planar fluorine-18-FDG imaging after recent myocardial infarction to assess myocardial viability.

UNLABELLED: The aim of this study was to define the clinical feasibility of planar myocardial 18F-fluorodeoxyglucose (FDG) imaging and to assess the relation between 201Tl, FDG and left ventricular function early after myocardial infarction. METHODS: Fifty-one patients were studied 5 +/- 2 days after infarction. Scintigraphic images were visually and quantitatively analyzed using a circumferential profiles technique. FDG uptake was normalized to the area with maximal 201Tl uptake. Scintigraphic data were compared with left ventricular wall motion as assessed by ventriculography in 22 patients. Relative regional 201Tl uptake was categorized as normal (> or = 75% of peak activity), moderately reduced (50%-75%) or severely reduced (< 50%). These tracer defects were considered viable if FDG uptake exceeded 201Tl uptake by > or = 20% and/or if FDG uptake was normal (> or = 75%). All regions with FDG uptake 20% less than 201Tl uptake were considered nonviable. RESULTS: Four hundred forty-one myocardial regions were analyzed; 200 showed normal 201Tl uptake, 241 had reduced uptake, 191 had moderately reduced 201Tl uptake and 50 regions had severely reduced uptake. Viability for moderately and severely reduced regions was observed in 62% and 48%, respectively. A concordance between flow and metabolism was observed in 38% and 52%, respectively. CONCLUSION: Myocardial FDG imaging is feasible with standard gamma camera systems and enables the identification of regions with preserved glucose metabolism in patients shortly after infarction.

The theoretical and experimental evaluation of the heat balance in perfused tissue.

Accurate treatment planning is necessary for the successful application of hyperthermia in the clinic. The validity of four different bioheat models or combinations of models is evaluated: the conventional bioheat transfer equation, the limited effective conductivity model, a mixed heat sink-effective conductivity model and a discrete vessel model. The heat balance for the heated volume, and especially the ratio between conductive heat removal and heat escape through the veins, is different for each of these models. Model predictions were compared with results from experiments on isolated perfused bovine tongues. Tongues were suspended in a water-filled container and heated by conduction. The steady state temperature distribution and heat balance were determined at various blood flow rates. Increased blood flow was found to lower the mean tissue temperature and to enhance both conductive and venous heat removal. This result agrees only with the mixed heat sink-effective conductivity and the discrete vessel model predictions. At low flow rates a modified heat sink term should be used because the venous efflux temperature was significantly lower than the mean tissue temperature.

Feasibility of assessing regional myocardial uptake of 18F-fluorodeoxyglucose using single photon emission computed tomography.

Differentiation between viable myocardium and scar tissue in segments with abnormal contraction has important consequences in the clinical management of patients with coronary artery disease. Positron emission tomography (PET) can identify viable tissue using 18F-fluorodeoxyglucose (FDG). However, application of PET for daily routine is limited. In this study, FDG uptake was visualized with single photon emission computed tomography (SPECT) and compared with regional perfusion assessed with thallium-201 (201Tl) SPECT. The scintigraphic findings were related to regional wall motion determined with two-dimensional echocardiography. Patients (n = 9) with wall motion abnormalities underwent FDG SPECT and resting 201Tl SPECT. To control the metabolic status patients were studied with a hyperinsulinaemic euglycemic clamp during FDG SPECT. Analysis of reconstructed data was performed visually and semiquantitatively using circumferential profiles. High-quality images were obtained. Eight 201Tl defects showed concordantly decreased FDG uptake (metabolism-perfusion matches) indicating scarred tissue, whereas six regions of hypoperfusion demonstrated a relatively increased FDG uptake (mismatches), suggesting viable myocardium. Semiquantitative analysis confirmed visual findings. Mean 201Tl and FDG activities were not significantly different in matching defects. In mismatches the mean FDG activity was 81 +/- 11% vs 64 +/- 9% mean 201Tl activity (P < 0.0001). In four of six segments with increased FDG uptake, two-dimensional echo revealed hypokinesia. Seven of eight regions with a matching defect in contrast were akinetic. Thus, in the areas with a mismatch contractility was preserved. We conclude that FDG uptake can be visualized with SPECT. Furthermore, our preliminary observations suggest that this approach can identify viable tissue.

Stunning does not change the relation between calcium and force in skinned rat trabeculae.

To test the hypothesis that stunning is due to a decreased sensitivity of the myofibrils for calcium, we compared the isometric force-Ca2+ relation in skinned trabeculae from stunned and control hearts. Hearts were made ischemic for 40 min followed by 30 min reperfusion. In one group (Group 1) changes in left ventricular systolic and diastolic pressure were monitored. From another group (Group 2), trabeculae were isolated to determine the relation between force and Ca2+ concentration. Trabeculae isolated from hearts (Group 3) perfused aerobically for 90 min served as controls. Left ventricular developed pressure and end diastolic pressure were 5.9 +/- 0.7 kPa and 5.8 +/- 0.7 kPa, respectively in stunned hearts as compared to 9.9 +/- 1.2 kPa and 1.2 +/- 0.1 kPa prior to ischemia. The nucleotide content decreased from 24.9 +/- 3.4 mumol.g-1(dw) in control hearts to 9.3 +/- 0.8 mumol.g-1(dw) after ischemia and reperfusion while the creatine kinase levels were about the same. Force-Ca2+ relations obtained from trabeculae from control and stunned hearts were fitted to the Hill equation. Maximal isometric force, the midpoint and the steepness of the curves estimated for the two groups were not significantly different. We conclude that the maximum isometric force and the sensitivity of the contractile apparatus of skinned myocardium of stunned hearts do not differ from that of control hearts. This suggests that structural changes of the contractile proteins leading to a decreased sensitivity of the myofibrils to calcium are not involved in the mechanism responsible for stunning.