A real-time marker of object-based attention in the human brain. A possible component of a "gate-keeping mechanism" performing late attentional selection in the Ventro-Lateral Prefrontal Cortex.

The decision to process an incoming stimulus attentively - and to trigger a follow-up cascade of high-level processes - is strategic for the human brain as it becomes transiently unavailable to subsequent stimulus processing. In this study, we set to identify brain networks that carry out such evaluations. We therefore assessed the time-course of neural responses with intracerebral EEG in human patients during an attentional reading task, contrasting to-be-attended vs. to-be-ignored items. We measured High-Frequency Activity [50-150 â€‹Hz] as a proxy of population-level spiking activity and we identified a crucial component of a Gate-Keeping Mechanism bilateral in the mid-Ventro-Lateral Prefrontal Cortex (VLPFC), at the interplay of the Ventral and Dorsal Attention Networks, that selectively reacts before domain specialized cortical regions that engage in full stimulus analysis according to task demands.

Respiratory-gated KES imaging of a rat model of acute lung injury at the Canadian Light Source.

In this study, contrast-enhanced X-ray tomographic imaging for monitoring and quantifying respiratory disease in preclinical rodent models is proposed. A K-edge imaging method has been developed at the Canadian Light Source to very accurately obtain measurements of the concentration of iodinated contrast agent in the pulmonary vasculature and inhaled xenon in the airspaces of rats. To compare the iodine and xenon concentration maps, a scout projection image was acquired to define the region of interest within the thorax for imaging and to ensure the same locations were imaged in each K-edge subtraction (KES) acquisition. A method for triggering image acquisition based on the real-time measurements of respiration was also developed to obtain images during end expiration when the lungs are stationary, in contrast to other previously published studies that alter the respiration to accommodate the image acquisition. In this study, images were obtained in mechanically ventilated animals using physiological parameters at the iodine K-edge in vivo and at the xenon K-edge post mortem (but still under mechanical ventilation). The imaging techniques were performed in healthy Brown Norway rats and in age-matched littermates that had an induced lung injury to demonstrate feasibility of the imaging procedures and the ability to correlate the lung injury and the quantitative measurements of contrast agent concentrations between the two KES images. The respiratory-gated KES imaging protocol can be easily adapted to image during any respiratory phase and is feasible for imaging disease models with compromised lung function.

Dose measurements for dental cone-beam CT: a comparison with MSCT and panoramic imaging.

To date there is a lack of published information on appropriate methods to determine patient doses from dental cone-beam computed tomography (CBCT) equipment. The goal of this study is to apply and extend the methods recommended in the American Association of Physicists in Medicine (AAPM) Report 111 for CBCT equipment to characterize dose and effective dose for a range of dental imaging equipment. A protocol derived from the one proposed by Dixon et al (2010 Technical Report 111, American Association of Physicist in Medicine, MD, USA), was applied to dose measurements of multi-slice CT, dental CBCT (small and large fields of view (FOV)) and a dental panoramic system. The computed tomography dose index protocol was also performed on the MSCT to compare both methods. The dose distributions in a cylindrical polymethyl methacrylate phantom were characterized using a thimble ionization chamber and Gafchromic™ film (beam profiles). Gafchromic™ films were used to measure the dose distribution in an anthropomorphic phantom. A method was proposed to extend dose estimates to planes superior and inferior to the central plane. The dose normalized to 100 mAs measured in the center of the phantom for the large FOV dental CBCT (11.4 mGy/100 mAs) is two times lower than that of MSCT (20.7 mGy/100 mAs) for the same FOV, but approximately 15 times higher than for a panoramic system (0.6 mGy/100 mAs). The effective dose per scan (in clinical conditions) found for the dental CBCT are 167.60 ± 3.62, 61.30 ± 3.88 and 92.86 ± 7.76 mSv for the Kodak 9000 (fixed scan length of 3.7 cm), and the iCAT Next Generation for 6 cm and 13 cm scan lengths respectively. The method to extend the dose estimates from the central slice to superior and inferior slices indicates a good agreement between theory and measurement. The Gafchromic™ films provided useful beam profile data and 2D distributions of dose in phantom.

Dosimetry protocol for the preclinical trials in white-beam minibeam radiation therapy.

PURPOSE: In the quest of a curative radiotherapy treatment for gliomas, new delivery modes are being explored. At the Biomedical Beamline of the European Synchrotron Radiation Facility, a new spatially fractionated technique, called minibeam radiation therapy (MBRT), is under development. The aims of this work were to assess different dosimetric aspects and to establish a dosimetry protocol to be applied in the forthcoming animal (rat) studies in order to evaluate the therapeutic index of this new radiotherapy approach. METHODS: Absolute dosimetry was performed with a thimble ionization chamber (PTW semiflex 31010) whose center was positioned at 2 g cm(-2) depth. To translate the dose measured in broad beam configuration to the dose deposited with a minibeam, the scatter factors were used. Those were assessed by using the Monte Carlo simulations and verified experimentally with Gafchromic films and a Bragg Peak chamber. The comparison of the theoretical and experimental data were used to benchmark the calculations. Finally, the dose distributions in a rat phantom were evaluated by using the validated Monte Carlo calculations. RESULTS: The absolute dosimetry in broad beam configuration was measured in reference conditions. The dose rate was in the range between 168 and 224 Gy∕min, depending on the storage ring current. A scatter factor of 0.80 ± 0.04 was obtained. Percentage depth dose and lateral profiles were evaluated both in homogenous and heterogeneous slab phantoms. The general good agreement between Monte Carlo simulations and experimental data permitted the benchmark of the calculations. Finally, the peak doses in the rat head phantom were assessed from the measurements in reference conditions. In addition, the peak-to-valley dose ratio values as a function of depth in the rat head were evaluated. CONCLUSIONS: A new promising radiotherapy approach is being explored at the ESRF: Minibeam Radiation Therapy. To assess the therapeutic index of this new modality, in vivo experiments are being planned, for which an accurate knowledge of the dosimetry is essential. For that purpose, a complete set of measurements and Monte Carlo simulations was performed. The first dosimetry protocol for preclinical trials in minibeam radiation therapy was established. This protocol allows to have reproducibility in terms of dose for the different biological studies.

Monochromatic minibeam radiotherapy: theoretical and experimental dosimetry for preclinical treatment plans.

Monochromatic x-ray minibeam radiotherapy is a new radiosurgery approach based on arrays of submillimetric interlaced planar x-ray beams. The aim of this study was to characterize the dose distributions obtained with this new modality when being used for preclinical trials. Monte Carlo simulations were performed in water phantoms. Percentage depth-dose curves and dose profiles were computed for single incidences and interleaved incidences of 80 keV planar x-ray minibeam (0.6 × 5 mm) arrays. Peak to valley dose ratios were also computed at various depths for an increasing number of minibeams. 3D experimental polymer gel (nPAG) dosimetry measurements were performed using MRI devices designed for small animal imaging. These very high spatial resolution (50 µm) dose maps were compared to the simulations. Preclinical minibeams dose distributions were fully characterized. Experimental dosimetry correlated well with Monte Carlo calculations (Student t-tests: p > 0.1). F98 tumor-bearing rats were also irradiated with interleaved minibeams (80 keV, prescribed dose: 25 Gy). This associated preclinical trial serves as a proof of principle of the technique. The mean survival time of irradiated glioma-bearing rats increased significantly, when compared to the untreated animals (59.6 ± 2.8 days versus 28.25 ± 0.75 days, p < 0.001).

[Synchroton radiotherapy]. / Radiothérapie par rayonnement synchrotron.

Radiation therapy is commonly used in the treatment of cancer. The normal tissue tolerance can be a limit to deliver enough dose to the tumor to be curative. The synchrotron beam presents some interesting physical properties, which could decrease this limitation. Synchrotron beam is a medium energy X-ray nearly parallel beam with high intensity. Three methods are under preclinical investigations: the microbeam, the minibeam and the stereotactic radiotherapy. The first two use a geometric irradiation effect called spatial fractioning. The last one use highly conformational irradiation geometry combined with a dose enhancement due to the presence of high-Z element in the target. Synchrotron radiotherapy preclinical experiments have shown some curative effect on rodent glioma models. Following these encouraging results a phase I/II clinical trial of iodinated enhanced stereotactic synchrotron radiotherapy is currently being prepared at the European Synchrotron Radiation Facility.

Microleakage of class V resin composite restorations after conventional and Er:YAG laser preparation.

This in vitro study compared the microleakage of Class V resin composite restorations at bevelled enamel/composite and dentin/composite interfaces following Er:YAG laser (pre-treatment modalities: laser-etching and/or acid-etching) or conventional preparation and acid-etch, in association with two resin composite formulations and their three-step adhesive system. Class V cavities with conventional bevel produced on the lingual and buccal surfaces of eighty extracted caries- and restoration-free human teeth, were assigned to eight groups: cavities were or Er:YAG-lased and acid-etched (groups 1 and 5); or Er:YAG-lased, laser-etched and acid-etched (groups 2 and 6); or Er:YAG-lased and only laser-etched (groups 3 and 7); or cut by dental drill at high-speed and acid-etched (groups 4 and 8). The specimens were restored with Optibond FL+Herculite XRV (groups 1, 2, 3 and 4) or with Scotchbond MP+Z 100 (groups 5, 6, 7 and 8), stored in distilled water at 37 degrees C for 24 h, thermocycled 1500 times between 5 and 55 degrees C, placed in a 2% aqueous solution of methylene blue for 24 h at 37 degrees C, embedded in resin and sectioned. Microleakage was assessed according to the depth of dye penetration along the restoration. There were statistically significant differences between occlusal and cervical regions for all groups (P<0.01) except for groups 3 and 7. Pair-wise comparison of groups showed that acid-etch is advocated when using resin composite in Er:YAG-lased Class V cavities; the seal at enamel margins in Er:YAG-lased and laser-etched cavities depended on the resin composite formulation and corresponding adhesive (P<0.05).

Basic fitting and evaluation parameters of a newly designed cochlear implant electrode.

OBJECTIVE: To validate a newly designed cochlear implant electrode (TRACE) in the standard monopolar mode and compare it to a patient group implanted with a standard Nucleus Contour cochlear implant electrode. The electrode contacts of the TRACE electrode have the same active surface area for stimulation, but the position in the scala tympani is different from that of the Nucleus Contour electrode. MATERIAL AND METHODS: The following parameters, used in cochlear implant fitting and evaluation procedures, were determined: the threshold and comfort stimulation current levels; the electrode impedances; and the phoneme discrimination and speech recognition scores using the ACE speech algorithm. CONCLUSION: The new electrode does not differ significantly from the standard Nucleus Contour electrode in terms of the investigated parameters within the test group.

Overview of safety imaging methods for newly designed cochlear implant electrodes.

Different individual test methods and protocols have been reported for the in-vitro evaluation of temporal bones implanted with newly designed cochlear implant electrodes, prior to human implantation. In practice, however, these methods may not always give the required information. In this study, a large battery of tests has been evaluated using the electrode as a fixed parameter. Standard clinical x-ray gave the best information to evaluate the electrode's position. Light microscopic evaluation and polishing technique studies proved to be the most valuable techniques to evaluate endocochlear damage.

Design, construction and mechanical optimisation process of electrode with radial current flow in the scala tympani.

A 48 contact cochlear implant electrode has been constructed for electrical stimulation of the auditory nerve. The stimulating contacts of this electrode are organised in two layers: 31 contacts on the upper surface directed towards the habenula perforata and 17 contacts connected together as one longitudinal contact on the underside. The design of the electrode carrier aims to make radial current flow possible in the cochlea. The mechanical structure of the newly designed electrode was optimised to obtain maximal insertion depth. Electrode insertion tests were performed in a transparent acrylic model of the human cochlea.

Acute ischemic dysfunction alters coronary flow reserve in remote nonischemic regions: potential mechanical etiology identified in an acute canine model.

BACKGROUND: Impaired coronary flow reserve (CFR) has been observed in remote nonischemic regions in patients after myocardial infarction. The mechanism for this impairment in remote nonischemic CFR remains undefined. This study evaluates the effect of progressive regional ischemic dysfunction on function in remote nonischemic regions, and the effect of the extent of dysfunction on remote nonischemic coronary flow and CFR. METHODS: In an anesthetized open-chest canine model (n = 7) of acute progressive distal and proximal left anterior descending (LAD) coronary artery occlusion, regional myocardial thickening fraction and coronary flow and CFR were measured with Doppler probes. CFR was assessed by an intracoronary injection of 36 microg of adenosine. Changes in thickening fraction and CFR were evaluated for isovolumic, ejection, and diastolic phases. Changes in resting regional flow were also assessed using radiolabeled microspheres. The extent of the ischemic area was defined as regions of myocardium with endocardial microsphere blood flow less than 0.3 mL/min/g. RESULTS: The ischemic area increased from 12% +/- 1% of left ventricle with distal occlusion to 30% +/- 2% of left ventricle with proximal occlusion (P < .001). The LAD thickening fraction decreased significantly from baseline (18% +/- 1%) to distal (-8% +/- 1%,) and proximal (-4% +/- 1%) occlusion (P < .001 for distal and proximal vs baseline). Isovolumic bulging in the LAD region was associated with a progressive increase in thickening fraction in the remote nonischemic left circumflex (LCX) artery region (baseline 12% +/- 1%; distal occlusion 15% +/- 2%, P = .014 vs baseline; proximal occlusion 17% +/- 2%, P = .02 vs baseline). Most of the increase in remote thickening fraction occurred during the isovolumic phase. There was no significant change in resting flow in remote nonischemic LCX regions or global hemodynamic parameters. However, there was a progressive decrease in remote nonischemic CFR (baseline 2.44 +/- 0.3), distal occlusion (2.19 +/- 0.31; P = .055 vs baseline), and proximal occlusion (1.79 +/- 0.22; P = 0.004 vs baseline, and P = .012 vs distal occlusion). A progressive decrease in CFR was noted in each phase of the cardiac cycle. CONCLUSION: In a canine model of acute progressive distal and proximal coronary occlusion, we observed a progressive decrease in CFR in remote nonischemic regions concurrent with an increase in the extent of ischemia. The decrease in remote nonischemic CFR was associated with ischemia-induced isovolumic bulging, which placed the remote regions at a mechanical disadvantage. These observations suggest a potential mechanical etiology for the observed impairment in remote CFR. Alterations in remote nonischemic CFR during acute ischemia may have important clinical implications for perfusion scintigraphy.

Quantification of SPECT myocardial perfusion images: methodology and validation of the Yale-CQ method.

BACKGROUND: Quantification of single photon emission computed tomography (SPECT) images is important for reproducible and accurate image interpretation. In addition, SPECT quantification provides important prognostic information. The purpose of this study was to validate the Yale circumferential quantification (Yale-CQ) method in phantom studies. METHODS: Myocardial perfusion defects of varying extent and severities were simulated in a cardiac phantom with fillable defect inserts. Forty-five different phantom configurations simulated 45 different myocardial perfusion defect sizes, ranging from 1.6% to 32% of the cardiac phantom volume. Automatic processing was compared with manual processing in the phantom SPECT studies. RESULTS: The automatic Yale-CQ algorithm performed well in all phantom studies. Compared with manual processing, the mean absolute error for automatically determined center of short axis slices was 0.27 pixel in the x direction, 0.45 pixel in the y direction, and 0.15 pixel in radius. Quantification of phantom defects with the Yale-CQ method correlated well with actual defect sizes (R = 0.99), but there was a systematic underestimation (mean error = -7.9%). With derived correction factors the overall correlation between 45 phantom defects and actual defect sizes was excellent, and the estimation error was significantly improved (R = 0.98, mean error = -0.82% for manual method and -0.95% for automatic method). CONCLUSION: The automatic processing algorithm performs well for the phantom studies. Myocardial perfusion abnormalities can be quantified accurately by use of the Yale-CQ method. Quantified SPECT defect size can be expressed as a percentage of the left ventricle.

Limitations of dobutamine for enhancing flow heterogeneity in the presence of single coronary stenosis: implications for technetium-99m-sestamibi imaging.

UNLABELLED: Dobutamine is used as an alternative to exercise in conjunction with 99mTc-sestamibi SPECT perfusion imaging for detection of coronary artery disease. However, the use of quantitative dobutamine 99mTc-sestamibi SPECT imaging for enhanced detection of coronary stenosis has not been established. The goal of this study is to examine the effects of dobutamine stress on regional myocardial blood flow and relative myocardial 99mTc-sestamibi activity in the presence of a single-vessel stenosis. METHODS: In six open-chest dogs with left circumflex artery stenosis, radiolabeled microspheres were injected during baseline, severe stenosis and peak dobutamine stress (10 microg/kg/min). Technetium-99m-sestamibi was injected intravenously at peak dobutamine. Hearts were excised 20 min after 99mTc-sestamibi injection for SPECT imaging and post-mortem gamma-well counting. RESULTS: Dobutamine significantly increased heart rate, rate-pressure product and the first derivative of left ventricular pressure. Ischemic zone (left circumflex) myocardial blood flows (in ml/min/g) were: baseline, 0.92 +/- 0.15; stenosis, 0.65 +/- 0.16; and dobutamine, 1.19 +/- 0.38. Nonischemic zone myocardial blood flows were: baseline, 0.99 +/- 0.18; stenosis, 1.01 +/- 0.12; and dobutamine, 1.94 +/- 0.32 (p < 0.01 versus stenosis). Ischemic flows, expressed as percentages of nonischemic flows, were: baseline, 94% +/- 2%; stenosis, 63% +/- 11% (p < 0.05 versus baseline) and dobutamine, 60% +/- 12% (p was not significant versus stenosis). Technetium-99m-sestamibi activity in the ischemic zone (75% +/- 6% nonischemic) underestimated the relative flow deficit produced during dobutamine stress (p = 0.056). Myocardial 99mTc-sestamibi activity correlated with flow when flow was less than 1.0 ml/min/g. At higher flow ranges (1.0 ml/min/g-3.5 ml/min/g), 99mTc-sestamibi did not track flow. CONCLUSION: In a canine model of flow-limiting, single-vessel stenosis, dobutamine (10 microg/kg/min) did not augment flow heterogeneity. In addition, relative myocardial 99mTc-sestamibi activity underestimated microsphere flow at higher flows induced by dobutamine, leading to underestimation of ischemia. These findings suggest that dobutamine stress 99mTc-sestamibi scintigraphy may underestimate the relative flow deficit.

Extracardiac activity complicates quantitative cardiac SPECT imaging using a simultaneous transmission-emission approach.

UNLABELLED: Increased extracardiac activity confounds conventional cardiac SPECT image reconstruction using a filtered backprojection method. Others have proposed that simultaneously acquired transmission-emission (STE) images that are reconstructed with a maximum likelihood (ML) method incorporating a nonuniform attenuation correction would less likely be affected by the presence of extracardiac activity. However, this approach corrects only for decreased myocardial counts from attenuation and not for increased myocardial counts from extracardiac activity. Therefore, STE with nonuniform attenuation correction may also result in reconstruction artifacts when extracardiac activity is present. METHODS: Acquisitions of phantoms with nonuniform and uniform attenuation were performed using STE and conventional approaches, in the absence and presence of extracardiac activity. All acquisitions used a triple-headed SPECT camera. STE acquisitions used fanbeam collimation and a 153Gd transmission source. STE images were reconstructed using ML, with and without nonuniform attenuation correction. Reconstructed short-axis images were quantitated, and percentage variability for each count profile was calculated. RESULTS: In a nonuniform phantom configuration, STE reconstruction with nonuniform attenuation correction significantly improved image uniformity. This improvement in image uniformity was diminished with the addition of increasing extracardiac activity. In a uniform phantom, STE reconstruction with nonuniform attenuation correction significantly improved uniformity only in the presence of extracardiac activity. CONCLUSION: The addition of attenuation correction in the presence of extracardiac activity can have complex effects on ML reconstruction with nonuniform attenuation correction, which depends on the amount of extracardiac activity and pattern of attenuation.

Comparison and reproducibility of visual echocardiographic and quantitative radionuclide left ventricular ejection fractions.

Left ventricular (LV) ejection fraction (EF) is commonly assessed by equilibrium radionuclide angiography and echocardiography. These methods are presumed to be interchangeable for this purpose. This study (1) compares quantification of LVEF by equilibrium radionuclide angiography with visual estimation of LVEF by echocardiography, (2) determines the reproducibility of both methods, and (3) evaluates whether differences in determinations of LVEF are of clinical relevance. Seventy-three clinically stable patients had both equilibrium radionuclide angiography and echocardiography performed within a 4-day period. LVEF by both techniques was compared after blinded analysis by 3 echocardiographers and 3 nuclear technologists. Reproducibility was assessed by blinded repeat analysis after a 1-week interval. The frequency of differences in repeat assessments of EF that the authors considered to be of potential clinical relevance (i.e., difference > or = 10% EF units) was assessed for both techniques. Correlation of LVEF determined by both methods was good (r = 0.81, SEE = 3.5) but with substantial differences in individual patients (limits of agreement, 23.6%). Intra- and inter-observer reproducibility was good for both methods, but better for radionuclide LVEF than for echocardiographic LVEF. Limits of agreement were substantially better for radionuclide LVEF than for echocardiographic LVEF (1.8% to 3.6% versus 13.4% to 17.4%, respectively). Clinically relevant differences did not occur on repeat processing of equilibrium radionuclide angiography. In contrast, potentially clinically relevant differences occurred in 8% to 26% of studies on repeat analysis of echocardiography. Thus, LVEF determined by equilibrium radionuclide angiography and echocardiography show good agreement. Both methods provide clinically valuable measurements for LV function. However, when a precisely reproducible measurement is required for patient management decisions, equilibrium radionuclide angiography is the method of choice.

Serotype, hemolysin production, and adherence characteristics of strains of Escherichia coli causing urinary tract infection in dogs.

Virulence factors were studied in 82 strains of Escherichia coli isolated from the urine of dogs with urinary tract infections. The most frequently expressed O antigens were 2, 4, 6, 25, and 22/83. Most strains were K nontypeable. Mannose-sensitive hemagglutination (MSH) with canine erythrocytes was observed in 71 strains and mannose-resistant hemagglutination (MRH) was observed in 32 strains. Strains that caused MSH of erythrocytes from dogs also caused MSH of erythrocytes from guinea pigs. Most strains that caused MRH of human A1P1 erythrocytes also reacted with erythrocytes of dogs. Of 22 strains (27%) that agglutinated human A1P1 erythrocytes, but not A1p erythrocytes, 17 (77%) had specificity for globo A, but did not react with the galactose alpha 1----4galactose beta disaccharide receptor. The remaining 5 strains and 2 others that simultaneously expressed an X adhesin agglutinated galactose alpha 1----4galactose beta-coated latex beads. Bacterial adherence to canine uroepithelial cells from the bladder was most often observed in strains expressing MSH, less often observed in strains expressing MRH, and least often observed in strains that failed to induce hemagglutination. Adherence of MSH strains to canine uroepithelial cells was inhibited by alpha-methyl-D-mannoside. As a group, MRH strains expressing globo-A- and galactose alpha 1----4galactose beta-specific adhesins did not have strong adherence. Strains of E coli isolated from dogs with urinary tract infections most commonly expressed type-1 fimbriae, and the main mechanism of in vitro adherence to canine uroepithelial cells involved a mannose-sensitive mechanism. Overrepresentation of globo-A-specific adhesins did not appear to be related to adherence of canine uroepithelial cells.

Appearance of hybridoma growth factor/interleukin-6 in the serum of mice bearing a methylcholanthrene-induced sarcoma.

Serum concentrations of hybridoma growth factor/interleukin-6 progressively increased in mice bearing a transplantable methylcholanthrene-induced sarcoma with tumor growth. Elevated HGF/interleukin-6 concentrations were also positively correlated with increased serum concentrations of the hepatic acute phase reactant protein, amyloid P. Daily Indomethacin treatment of sarcoma-bearing mice prolonged survival and reduced the magnitude of the serum amyloid P response, but failed to attenuate either tumor growth or serum HGF/interleukin-6 responses. Since previous studies have demonstrated that neither interleukin-1 nor tumor necrosis factor-alpha can be detected in the serum of these sarcoma-bearing mice, and that HGF/interleukin-6 is a principal mediator of the hepatic acute phase response, we conclude that circulating HGF/interleukin-6 may contribute significantly to the host responses which accompany experimentally-introduced cancer. Furthermore, prostanoid inhibition does not appear to regulate the synthesis and release of HGF/interleukin-6 during tumor growth.