Radiologic Patterns of Necrosis After Proton Therapy of Skull Base Tumors

Background: Discrimination between radiation necrosis and tumor progression after radiation therapy represents a radiologic challenge. The aim of our investigation is to identify patterns of radiation necrosis on brain magnetic resonance imaging (MRI) and positron emission tomography (PET) with Fluoroethyltyrosin (FET) after proton beam therapy (PBT) for skull base tumors. Material and Methods: Five consecutive patients with extra-axial neoplasms were included, presenting a total of eight radiation necrosis lesions (three clival chordomas; two petroclival chondrosarcomas; two women; mean age: 49 ± 18.2 years). Radiation necrosis was defined as the appearance of abnormal enhancement on MRI after PBT decreasing over time, and additional histopathologic confirmation in one patient. MRI and PET imaging were retrospectively analyzed by two experienced radiologists in consensus. Results: All lesions were localized close to the primary tumor in the field of irradiation. Three patients showed bilateral symmetrical lesions. All lesions showed T2 hyperintensity and T1 hypointensity. Cerebral blood volume (CBV) was reduced in all available studies. None of the lesions showed a restricted diffusion. FET-PET (three patients) showed a higher uptake in four out of five lesions; three of which had a mean tumor-to-background (TBRmean) uptake lower than 1.95 and FET uptake increasing over time and were correctly classified into radiation necrosis. Conclusions: Most radiation necroses were in direct continuity with the primary tumor mimicking tumor progression. The most consistent imaging findings for PBT radiation necrosis are low CBV without restricted diffusion and FET-PET TBRmean lower than 1.95 or increasing uptake over time. Bilateral symmetric involvement may be another indicator of radiation necrosi

Absolute Calibration and Characterization of the Multiband Imaging Photometer for Spitzer. II. 70 micron Imaging

The absolute calibration and characterization of the Multiband Imaging Photometer for Spitzer (MIPS) 70 micron coarse- and fine-scale imaging modes are presented based on over 2.5 years of observations. Accurate photometry (especially for faint sources) requires two simple processing steps beyond the standard data reduction to remove long-term detector transients. Point spread function (PSF) fitting photometry is found to give more accurate flux densities than aperture photometry. Based on the PSF fitting photometry, the calibration factor shows no strong trend with flux density, background, spectral type, exposure time, or time since anneals. The coarse-scale calibration sample includes observations of stars with flux densities from 22 mJy to 17 Jy, on backgrounds from 4 to 26 MJy sr^-1, and with spectral types from B to M. The coarse-scale calibration is 702 +/- 35 MJy sr^-1 MIPS70^-1 (5% uncertainty) and is based on measurements of 66 stars. The instrumental units of the MIPS 70 micron coarse- and fine-scale imaging modes are called MIPS70 and MIPS70F, respectively. The photometric repeatability is calculated to be 4.5% from two stars measured during every MIPS campaign and includes variations on all time scales probed. The preliminary fine-scale calibration factor is 2894 +/- 294 MJy sr^-1 MIPS70F^-1 (10% uncertainty) based on 10 stars. The uncertainty in the coarse- and fine-scale calibration factors are dominated by the 4.5% photometric repeatability and the small sample size, respectively. The 5-sigma, 500 s sensitivity of the coarse-scale observations is 6-8 mJy. This work shows that the MIPS 70 micron array produces accurate, well calibrated photometry and validates the MIPS 70 micron operating strategy, especially the use of frequent stimulator flashes to track the changing responsivities of the Ge:Ga detectors.Comment: 19 pages, PASP, in pres

Multivariate Pattern Recognition for Diagnosis and Prognosis in Clinical Neuroimaging: State of the Art, Current Challenges and Future Trends

Many diseases are associated with systematic modifications in brain morphometry and function. These alterations may be subtle, in particular at early stages of the disease progress, and thus not evident by visual inspection alone. Group-level statistical comparisons have dominated neuroimaging studies for many years, proving fascinating insight into brain regions involved in various diseases. However, such group-level results do not warrant diagnostic value for individual patients. Recently, pattern recognition approaches have led to a fundamental shift in paradigm, bringing multivariate analysis and predictive results, notably for the early diagnosis of individual patients. We review the state-of-the-art fundamentals of pattern recognition including feature selection, cross-validation and classification techniques, as well as limitations including inter-individual variation in normal brain anatomy and neurocognitive reserve. We conclude with the discussion of future trends including multi-modal pattern recognition, multi-center approaches with data-sharing and cloud-computing

Analysis of continuous neuronal activity evoked by natural speech with computational corpus linguistics methods

In the field of neurobiology of language, neuroimaging studies are generally based on stimulation paradigms consisting of at least two different conditions. Designing those paradigms can be very time-consuming and this traditional approach is necessarily data-limited. In contrast, in computational and corpus linguistics, analyses are often based on large text corpora, which allow a vast variety of hypotheses to be tested by repeatedly re-evaluating the data set. Furthermore, text corpora also allow exploratory data analysis in order to generate new hypotheses. By drawing on the advantages of both fields, neuroimaging and computational corpus linguistics, we here present a unified approach combining continuous natural speech and MEG to generate a corpus of speech-evoked neuronal activity

Fusion pore expansion is a slow, discontinuous, and Ca2+-dependent process regulating secretion from alveolar type II cells

In alveolar type II cells, the release of surfactant is considerably delayed after the formation of exocytotic fusion pores, suggesting that content dispersal may be limited by fusion pore diameter and subject to regulation at a postfusion level. To address this issue, we used confocal FRAP and N-(3-triethylammoniumpropyl)-4-(4-[dibutylamino]styryl) pyridinium dibromide (FM 1-43), a dye yielding intense localized fluorescence of surfactant when entering the vesicle lumen through the fusion pore (Haller, T., J. Ortmayr, F. Friedrich, H. Volkl, and P. Dietl. 1998. Proc. Natl. Acad. Sci. USA. 95:1579–1584). Thus, we have been able to monitor the dynamics of individual fusion pores up to hours in intact cells, and to calculate pore diameters using a diffusion model derived from Fick's law. After formation, fusion pores were arrested in a state impeding the release of vesicle contents, and expanded at irregular times thereafter. The expansion rate of initial pores and the probability of late expansions were increased by elevation of the cytoplasmic Ca2+ concentration. Consistently, content release correlated with the occurrence of Ca2+ oscillations in ATP-treated cells, and expanded fusion pores were detectable by EM. This study supports a new concept in exocytosis, implicating fusion pores in the regulation of content release for extended periods after initial formation

Neuroimaging of dementia in 2013: what radiologists need to know

The structural and functional neuroimaging of dementia have substantially evolved over the last few years. The most common forms of dementia, Alzheimer disease (AD), Lewy body dementia (LBD) and fronto-temporal lobar degeneration (FTLD), have distinct patterns of cortical atrophy and hypometabolism that evolve over time, as reviewed in the first part of this article. The second part discusses unspecific white matter alterations on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images as well as cerebral microbleeds, which often occur during normal aging and may affect cognition. The third part summarises molecular neuroimaging biomarkers recently developed to visualise amyloid deposits, tau protein deposits and neurotransmitter systems. The fourth section reviews the utility of advanced image analysis techniques as predictive biomarkers of cognitive decline in individuals with early symptoms compatible with mild cognitive impairment (MCI). As only about half of MCI cases will progress to clinically overt dementia, whereas the other half remain stable or might even improve, the discrimination of stable versus progressive MCI is of paramount importance for both individual patient treatment and patient selection for clinical trials. The fifth and final part discusses the inter-individual variation in the neurocognitive reserve, which is a potential constraint for all proposed methods. Key Points • Many forms of dementia have spatial atrophy patterns detectable on neuroimaging. • Early treatment of dementia is beneficial, indicating the need for early diagnosis. • Advanced image analysis techniques detect subtle anomalies invisible on radiological evaluation. • Inter-individual variation explains variable cognitive impairment despite the same degree of atroph

Neuroimaging of dementia in 2013: what radiologists need to know

The structural and functional neuroimaging of dementia have substantially evolved over the last few years. The most common forms of dementia, Alzheimer disease (AD), Lewy body dementia (LBD) and fronto-temporal lobar degeneration (FTLD), have distinct patterns of cortical atrophy and hypometabolism that evolve over time, as reviewed in the first part of this article. The second part discusses unspecific white matter alterations on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images as well as cerebral microbleeds, which often occur during normal aging and may affect cognition. The third part summarises molecular neuroimaging biomarkers recently developed to visualise amyloid deposits, tau protein deposits and neurotransmitter systems. The fourth section reviews the utility of advanced image analysis techniques as predictive biomarkers of cognitive decline in individuals with early symptoms compatible with mild cognitive impairment (MCI). As only about half of MCI cases will progress to clinically overt dementia, whereas the other half remain stable or might even improve, the discrimination of stable versus progressive MCI is of paramount importance for both individual patient treatment and patient selection for clinical trials. The fifth and final part discusses the inter-individual variation in the neurocognitive reserve, which is a potential constraint for all proposed methods. Key Points • Many forms of dementia have spatial atrophy patterns detectable on neuroimaging. • Early treatment of dementia is beneficial, indicating the need for early diagnosis. • Advanced image analysis techniques detect subtle anomalies invisible on radiological evaluation. • Inter-individual variation explains variable cognitive impairment despite the same degree of atroph

Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European Economic Area in 2015: a population-level modelling analysis

Background: Infections due to antibiotic-resistant bacteria are threatening modern health care. However, estimating their incidence, complications, and attributable mortality is challenging. We aimed to estimate the burden of infections caused by antibiotic-resistant bacteria of public health concern in countries of the EU and European Economic Area (EEA) in 2015, measured in number of cases, attributable deaths, and disability-adjusted life-years (DALYs). Methods: We estimated the incidence of infections with 16 antibiotic resistance–bacterium combinations from European Antimicrobial Resistance Surveillance Network (EARS-Net) 2015 data that was country-corrected for population coverage. We multiplied the number of bloodstream infections (BSIs) by a conversion factor derived from the European Centre for Disease Prevention and Control point prevalence survey of health-care-associated infections in European acute care hospitals in 2011–12 to estimate the number of non-BSIs. We developed disease outcome models for five types of infection on the basis of systematic reviews of the literature. Findings: From EARS-Net data collected between Jan 1, 2015, and Dec 31, 2015, we estimated 671 689 (95% uncertainty interval [UI] 583 148–763 966) infections with antibiotic-resistant bacteria, of which 63·5% (426 277 of 671 689) were associated with health care. These infections accounted for an estimated 33 110 (28 480–38 430) attributable deaths and 874 541 (768 837–989 068) DALYs. The burden for the EU and EEA was highest in infants (aged <1 year) and people aged 65 years or older, had increased since 2007, and was highest in Italy and Greece. Interpretation: Our results present the health burden of five types of infection with antibiotic-resistant bacteria expressed, for the first time, in DALYs. The estimated burden of infections with antibiotic-resistant bacteria in the EU and EEA is substantial compared with that of other infectious diseases, and has increased since 2007. Our burden estimates provide useful information for public health decision-makers prioritising interventions for infectious diseases