Dobutamine stress cardiovascular magnetic resonance at 3 Tesla

<p>Abstract</p> <p>Purpose</p> <p>The assessment of inducible wall motion abnormalities during high-dose dobutamine-stress cardiovascular magnetic resonance (DCMR) is well established for the identification of myocardial ischemia at 1.5 Tesla. Its feasibility at higher field strengths has not been reported. The present study was performed to prospectively determine the feasibility and diagnostic accuracy of DCMR at 3 Tesla for depicting hemodynamically significant coronary artery stenosis (≥ 50% diameter stenosis) in patients with suspected or known coronary artery disease (CAD).</p> <p>Materials and methods</p> <p>Thirty consecutive patients (6 women) (66 ± 9.3 years) were scheduled for DCMR between January and May 2007 for detection of coronary artery disease. Patients were examined with a Philips Achieva 3 Tesla system (Philips Healthcare, Best, The Netherlands), using a spoiled gradient echo cine sequence. Technical parameters were: spatial resolution 2 × 2 × 8 mm³, 30 heart phases, spoiled gradient echo TR/TE: 4.5/2.6 msec, flip angle 15°. Images were acquired at rest and stress in accordance with a standardized high-dose dobutamine-atropine protocol during short breath-holds in three short and three long-axis views. Dobutamine was administered using a standard protocol (10 μg increments every 3 minutes up to 40 μg dobutamine/kg body weight/minute plus atropine if required to reach target heart rate). The study protocol included administration of 0.1 mmol/kg/body weight Gd-DTPA before the cine images at rest were acquired to improve the image quality. The examination was terminated if new or worsening wall-motion abnormalities or chest pain occurred or when > 85% of age-predicted maximum heart rate was reached. Myocardial ischemia was defined as new onset of wall-motion abnormality in at least one segment. In addition, late gadolinium enhancement (LGE) was performed. Images were evaluated by two blinded readers. Diagnostic accuracy was determined with coronary angiography as the reference standard. Image quality and wall-motion at rest and maximum stress level were evaluated using a four-point scale.</p> <p>Results</p> <p>In 27 patients DCMR was performed successfully, no patient had to be excluded due to insufficient image quality. Twenty-two patients were examined by coronary angiography, which depicted significant stenosis in 68.2% of the patients. Patient-based sensitivity and specificity were 80.0% and 85.7% respectively and accuracy was 81.8%. Interobserver variability for assessment of wall motion abnormalities was 88% (κ = 0.760; p < 0.0001). Negative and positive predictive values were 66.7% and 92.3%, respectively. No significant differences in average image quality at rest versus stress for short or long-axis cine images were found.</p> <p>Conclusion</p> <p>High-dose DCMR at 3T is feasible and an accurate method to depict significant coronary artery stenosis in patients with suspected or known CAD.</p

Overweight/Obesity and Respiratory and Allergic Disease in Children: International Study of Asthma and Allergies in Childhood (ISAAC) Phase Two

BackgroundChildhood obesity and asthma are increasing worldwide. A possible link between the two conditions has been postulated.MethodsCross-sectional studies of stratified random samples of 8–12-year-old children (n = 10 652) (16 centres in affluent and 8 centres in non-affluent countries) used the standardized methodology of ISAAC Phase Two. Respiratory and allergic symptoms were ascertained by parental questionnaires. Tests for allergic disease were performed. Height and weight were measured, and overweight and obesity were defined according to international definitions. Prevalence rates and prevalence odds ratios were calculated.ResultsOverweight (odds ratio = 1.14, 95%-confidence interval: 0.98; 1.33) and obesity (odds ratio = 1.67, 95%-confidence interval: 1.25; 2.21) were related to wheeze. The relationship was stronger in affluent than in non-affluent centres. Similar results were found for cough and phlegm, rhinitis and eczema but the associations were mostly driven by children with wheeze. There was a clear association of overweight and obesity with airways obstruction (change in FEV1/FVC, −0.90, 95%-confidence interval: −1.33%; −0.47%, for overweight and −2.46%, 95%-confidence interval: −3.84%; −1.07%, for obesity) whereas the results for the other objective markers, including atopy, were null.ConclusionsOur data from a large international child population confirm that there is a strong relation of body mass index with wheeze especially in affluent countries. Moreover, body mass index is associated with an objective marker of airways obstruction (FEV1/FVC) but no other objective markers of respiratory and allergic disorders

Combined magnetic resonance coronary artery imaging, myocardial perfusion and late gadolinium enhancement in patients with suspected coronary artery disease

<p>Abstract</p> <p>Background</p> <p>Cardiovascular Magnetic Resonance (CMR) imaging offers methods for the detection of ischemia and myocardial infarction as well as visualization of the coronary arteries (MRCA). However, a direct comparison of adenosine perfusion (PERF), late gadolinium enhancement (LGE) and MRCA or the results of their combination has not been performed. Aim of the study was to evaluate the feasibility/diagnostic performance of rest/stress perfusion, late gadolinium enhancement and MRCA and their combination in patients with suspected coronary artery disease (CAD) in comparison to invasive angiography.</p> <p>Methods</p> <p>Fifty-four patients (60 ± 10 years, 35 men, CAD 48%) underwent CMR including MRCA (steady state free precession, navigator whole heart approach, spatial resolution 0.7 × 0.7 × .0.9 mm, trigger delay and temporal resolution adjusted individually), stress PERF (adenosine 140 μg/min/kg), rest PERF (SSFP, 3 short axis, 1 saturation prepulse per slice) and LGE (3D inversion recovery technique) using Gd-BOPTA. Images were analyzed visually. Stenosis >50% in invasive angiography was considered significant.</p> <p>Results</p> <p>Mean study time was 68 ± 11 minutes. Sensitivity for PERF, LGE, MRCA and the combination of PERF/LGE and PERF/LGE/MRCA was 87%, 50%, 91%, 88% and 92%, respectively and specificity 88%, 96%, 46%, 88% and 56%, respectively. If image quality of MRCA was excellent (n = 18) the combination of MRCA/PERF/LGE yield a sensitivity of 86% and specificity of 91%. However, no test or combination improved diagnostic performance significantly compared to PERF alone.</p> <p>Conclusion</p> <p>In patients with CAD, the combination of stress PERF, LGE and MRCA is feasible. When compared to invasive angiography, adenosine stress perfusion outperforms CMR coronary angiography in direct comparison and yields the best results with non-significant improvement in combination with LGE and significant deterioration in combination with MRCA. MRCA may be of additional value only in a minority of patients with excellent image quality.</p

Evolutionary and pulsational properties of white dwarf stars

Abridged. White dwarf stars are the final evolutionary stage of the vast majority of stars, including our Sun. The study of white dwarfs has potential applications to different fields of astrophysics. In particular, they can be used as independent reliable cosmic clocks, and can also provide valuable information about the fundamental parameters of a wide variety of stellar populations, like our Galaxy and open and globular clusters. In addition, the high densities and temperatures characterizing white dwarfs allow to use these stars as cosmic laboratories for studying physical processes under extreme conditions that cannot be achieved in terrestrial laboratories. They can be used to constrain fundamental properties of elementary particles such as axions and neutrinos, and to study problems related to the variation of fundamental constants. In this work, we review the essentials of the physics of white dwarf stars. Special emphasis is placed on the physical processes that lead to the formation of white dwarfs as well as on the different energy sources and processes responsible for chemical abundance changes that occur along their evolution. Moreover, in the course of their lives, white dwarfs cross different pulsational instability strips. The existence of these instability strips provides astronomers with an unique opportunity to peer into their internal structure that would otherwise remain hidden from observers. We will show that this allows to measure with unprecedented precision the stellar masses and to infer their envelope thicknesses, to probe the core chemical stratification, and to detect rotation rates and magnetic fields. Consequently, in this work, we also review the pulsational properties of white dwarfs and the most recent applications of white dwarf asteroseismology.Comment: 85 pages, 28 figures. To be published in The Astronomy and Astrophysics Revie

Modulating gradients in regulatory signals within mesenchymal stem cell seeded hydrogels: a novel strategy to engineer zonal articular cartilage.

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Engineering organs and tissues with the spatial composition and organisation of their native equivalents remains a major challenge. One approach to engineer such spatial complexity is to recapitulate the gradients in regulatory signals that during development and maturation are believed to drive spatial changes in stem cell differentiation. Mesenchymal stem cell (MSC) differentiation is known to be influenced by both soluble factors and mechanical cues present in the local microenvironment. The objective of this study was to engineer a cartilaginous tissue with a native zonal composition by modulating both the oxygen tension and mechanical environment thorough the depth of MSC seeded hydrogels. To this end, constructs were radially confined to half their thickness and subjected to dynamic compression (DC). Confinement reduced oxygen levels in the bottom of the construct and with the application of DC, increased strains across the top of the construct. These spatial changes correlated with increased glycosaminoglycan accumulation in the bottom of constructs, increased collagen accumulation in the top of constructs, and a suppression of hypertrophy and calcification throughout the construct. Matrix accumulation increased for higher hydrogel cell seeding densities; with DC further enhancing both glycosaminoglycan accumulation and construct stiffness. The combination of spatial confinement and DC was also found to increase proteoglycan-4 (lubricin) deposition toward the top surface of these tissues. In conclusion, by modulating the environment through the depth of developing constructs, it is possible to suppress MSC endochondral progression and to engineer tissues with zonal gradients mimicking certain aspects of articular cartilage.Funding was provided by Science Foundation Ireland (President of Ireland Young Researcher Award: 08/Y15/B1336) and the European Research Council (StemRepair – Project number 258463)

Light-evoked Somatosensory Perception of Transgenic Rats That Express Channelrhodopsin-2 in Dorsal Root Ganglion Cells

In vertebrate somatosensory systems, each mode of touch-pressure, temperature or pain is sensed by sensory endings of different dorsal root ganglion (DRG) neurons, which conducted to the specific cortical loci as nerve impulses. Therefore, direct electrical stimulation of the peripheral nerve endings causes an erroneous sensation to be conducted by the nerve. We have recently generated several transgenic lines of rat in which channelrhodopsin-2 (ChR2) transgene is driven by the Thy-1.2 promoter. In one of them, W-TChR2V4, some neurons were endowed with photosensitivity by the introduction of the ChR2 gene, coding an algal photoreceptor molecule. The DRG neurons expressing ChR2 were immunohistochemically identified using specific antibodies to the markers of mechanoreceptive or nociceptive neurons. Their peripheral nerve endings in the plantar skin as well as the central endings in the spinal cord were also examined. We identified that ChR2 is expressed in a certain population of large neurons in the DRG of W-TChR2V4. On the basis of their morphology and molecular markers, these neurons were classified as mechanoreceptive but not nociceptive. ChR2 was also distributed in their peripheral sensory nerve endings, some of which were closely associated with CK20-positive cells to form Merkel cell-neurite complexes or with S-100-positive cells to form structures like Meissner's corpuscles. These nerve endings are thus suggested to be involved in the sensing of touch. Each W-TChR2V4 rat showed a sensory-evoked behavior in response to blue LED flashes on the plantar skin. It is thus suggested that each rat acquired an unusual sensory modality of sensing blue light through the skin as touch-pressure. This light-evoked somatosensory perception should facilitate study of how the complex tactile sense emerges in the brain

Meta-analysis of the diagnostic performance of stress perfusion cardiovascular magnetic resonance for detection of coronary artery disease

<p>Abstract</p> <p>Aim</p> <p>Evaluation of the diagnostic accuracy of stress perfusion cardiovascular magnetic resonance for the diagnosis of significant obstructive coronary artery disease (CAD) through meta-analysis of the available data.</p> <p>Methodology</p> <p>Original articles in any language published before July 2009 were selected from available databases (MEDLINE, Cochrane Library and BioMedCentral) using the combined search terms of magnetic resonance, perfusion, and coronary angiography; with the exploded term coronary artery disease. Statistical analysis was only performed on studies that: (1) used a [greater than or equal to] 1.5 Tesla MR scanner; (2) employed invasive coronary angiography as the reference standard for diagnosing significant obstructive CAD, defined as a [greater than or equal to] 50% diameter stenosis; and (3) provided sufficient data to permit analysis.</p> <p>Results</p> <p>From the 263 citations identified, 55 relevant original articles were selected. Only 35 fulfilled all of the inclusion criteria, and of these 26 presented data on patient-based analysis. The overall patient-based analysis demonstrated a sensitivity of 89% (95% CI: 88-91%), and a specificity of 80% (95% CI: 78-83%). Adenosine stress perfusion CMR had better sensitivity than with dipyridamole (90% (88-92%) versus 86% (80-90%), P = 0.022), and a tendency to a better specificity (81% (78-84%) versus 77% (71-82%), P = 0.065).</p> <p>Conclusion</p> <p>Stress perfusion CMR is highly sensitive for detection of CAD but its specificity remains moderate.</p

Genomic profiling of CHEK2*1100delC-mutated breast carcinomas

Background: CHEK2*1100delC is a moderate-risk breast cancer susceptibility allele with a high prevalence in the Netherlands. We performed copy number and gene expression profiling to investigate whether CHEK2*1100delC breast cancers harbor characteristic genomic aberrations, as seen for BRCA1 mutated breast cancers. Methods: We performed high-resolution SNP array and gene expression profiling of 120 familial breast carcinomas selected from a larger cohort of 155 familial breast tumors, including BRCA1, BRCA2, and CHEK2 mutant tumors. Gene expression analyses based on a mRNA immune signature was used to identify samples with relative low amounts of tumor infiltrating lymphocytes (TILs), which were previously found to disturb tumor copy number and LOH (loss of heterozygosity) profiling. We specifically compared the genomic and gene expression profiles of CHEK2*1100delC breast cancers (n = 14) with BRCAX (familial non-BRCA1/BRCA2/CHEK2*1100delC mutated) breast cancers (n = 34) of the luminal intrinsic subtypes for which both SNP-array and gene expression data is available. Results: High amounts of TILs were found in a relatively small number of luminal breast cancers as compared to breast cancers of the basal-like subtype. As expected, the