Comparison of edge analysis techniques for the determination of the MTF of digital radiographic systems

The modulation transfer function (MTF) is well established as a metric to characterize the resolution performance of a digital radiographic system. Implemented by various laboratories, the edge technique is currently the most widespread approach to measure the MTF. However, there can be differences in the results attributed to differences in the analysis technique employed. The objective of this study was to determine whether comparable results can be obtained from different algorithms processing identical images representative of those of current digital radiographic systems. Five laboratories participated in a round-robin evaluation of six different algorithms including one prescribed in the International Electrotechnical Commission (IEC) 62220-1 standard. The algorithms were applied to two synthetic and 12 real edge images from different digital radiographic systems including CR, and direct- and indirect-conversion detector systems. The results were analysed in terms of variability as well as accuracy of the resulting presampled MTFs. The results indicated that differences between the individual MTFs and the mean MTF were largely below 0.02. In the case of the two simulated edge images, all algorithms yielded similar results within 0.01 of the expected true MTF. The findings indicated that all algorithms tested in this round-robin evaluation, including the IEC-prescribed algorithm, were suitable for accurate MTF determination from edge images, provided the images are not excessively noisy. The agreement of the MTF results was judged sufficient for the measurement of the MTF necessary for the determination of the DQE.     

Target motion measurement without implanted markers and its validation by comparison with manually obtained data

For an effective radiotherapy the exact tumor location must be determined. The localization has to take into account patient's setup position as well as internal organ motion. Among the different localization methods, the use of a computer tomography (CT) scanner in the therapy room has been proposed recently. Achieving a CT with the patient on the therapy couch, a patient's treatment position is captured. We present a method to locate tumor considering internal organ motion and displacements due to respiration. We tested the method with prostate and lung patients. The method found the most probable tumor position as well as, for high-mobility tumors located in the lung, its trajectory during the respiratory cycle. The results of this novel method were validated by comparison with manually determined target position.     

Genetic variability of the extraneuronal monoamine transporter EMT (SLC22A3)

The extraneuronal monoamine transporter EMT (HGNC Nomenclature SLC22A3) is the molecular correlate of the classical uptake₂ system responsible for the non-neuronal inactivation of circulating and centrally released catecholamines. Because of its functional profile and expression pattern, EMT is regarded as a candidate gene for diseases related to the sympathetic nervous system and neuropsychiatric disorders. We describe the first investigation of the genetic variability of the EMT gene in human. Six single-nucleotide substitutions and one deletion were detected within the assumed core promoter, the exonic and flanking intronic sequences and the 3'-untranslated region in 100 Caucasian individuals. No amino acid changes were found and Tajima's D was positive (D=2.91; P<0.01). However, the synonymous nucleotide substitution 1233G→A might serve as a cryptic splice acceptor site. Analysis of linkage disequilibrium between polymorphisms yielded 12 possible haplotypes accounting for more than 90% of all haplotypes. Knowledge of the sequence variation and frequency of the underlying polymorphisms in this member of the amphiphilic solute facilitator family of transporters provides the basis for subsequent association studies and candidate gene approaches. Electronic Publication     

The dual role of IL-10

Classification of cytokines as pro-versus anti-inflammatory might not apply to the pleiotropic effects of interleukin-10 (IL-10). Several reports suggest that IL-10 enhances the function of natural killer cells, which leads, through pathogen destruction, to increased antigen availability. In addition, by inhibiting the maturation of antigen-presenting cells (APCs), IL-10 preserves their ability for antigen uptake while simultaneously hampering their migration to draining lymph nodes. This review suggests that this "antigen-loading" phase might constitute an important component of the innate immune reaction to a pathogen. Additional proinflammatory stimuli might subsequently lead to maturation of "loaded" APCs that could migrate to draining lymph nodes or recruit and activate adaptive immune effectors locally.     

Central nervous system inflammatory response after cerebral infarction as detected by magnetic resonance imaging

Brain inflammation contributes to the tissue injury caused by ischemic stroke. Macrophages as the most abundant inflammatory cell population in stroke lesions can be visualized using ultrasmall superparamagnetic iron oxide (USPIO) as a cell-specific contrast agent for magnetic resonance imaging (MRI). The aim of our present study was to delineate the inflammatory response during experimental cerebral infarction by means of USPIO-enhanced MRI and to correlate the spatial distribution of USPIO-induced MR signal alterations with cellular infiltration and iron deposition. To this end USPIOs were administered to Wistar rats 5 days after photothrombotic cerebral infarction. MR imaging at 7 T performed 24 h later displayed a rim-like signal loss around the infarction in the USPIO treated animals. On histological brain sections obtained from the same animals after MRI the distribution of iron and ED1+ phagocytes was in full spatial agreement with the signal loss seen on T2*-weighted images. Our study validates USPIO-enhanced MRI as an important tool for the noninvasive visualization of brain inflammation in stroke and other CNS pathologies.     

A comparison of murine and human immunoproteomes of Helicobacter pylori validates the preclinical murine infection model for antigen screening

Preclinical mouse infection models are widely used for Helicobacter vaccine development, but how well such models mimic important aspects of human infections is unknown. A comparison of Helicobacter pylori immunoproteomes of infected mice with previously reported patient data reveals a high agreement in the antigens recognized, suggesting that H. pylori in vivo protein composition and recognition by the host immune system are comparable in mice and humans. Murine Helicobacter models may thus be valid to screen antigens for human vaccination.     

Molecular characterization of BCL6 breakpoints in primary diffuse large B-cell lymphomas of the central nervous system identifies GAPD as novel translocation partner

Primary central nervous system lymphomas (PCNSL) constitute diffuse large B-cell lymphomas arising in and remaining confined to the brain. Little information is available on cytogenetic changes in PCNSL, and recurrent chromosomal translocations have not yet been identified. Fluorescence in situ hybridization (FISH) of a series of 13 PCNSL from immunocompetent patients revealed 3 cases with signal patterns of a BCL6-specific probe suggesting a breakpoint in this oncogene locus in chromosome band 3q27. Here, we describe cloning of the translocation breakpoints by long-distance inverse polymerase chain reaction (LDI-PCR) in 2 of these tumors. Both breakpoints affected the first intron of BCL6. In one PCNSL, the HSPCA (HSP90A) gene in 14q32.31 was identified as BCL6 partner. In the second lymphoma, the gene encoding glyceraldehyde-3-phosphate dehydrogenase (GAPD) on 12p13.31 was detected as a hitherto unknown partner of BCL6. Our results suggest translocation-mediated BCL6 oncogene activation as a so far unknown pathogenetically relevant mechanism in PCNSL.