G. Gemme

Local MRI analysis approach in the diagnosis of early and prodromal Alzheimer's disease☆

BACKGROUND Medial temporal lobe (MTL) atrophy is one of the key biomarkers to detect early neurodegenerative changes in the course of Alzheimers disease (AD). There is active research aimed at identifying automated methodologies able to extract accurate classification indexes from T1-weighted magnetic resonance images (MRI). Such indexes should be fit for identifying AD patients as early as possible. SUBJECTS A reference group composed of 144AD patients and 189 age-matched controls was used to train and test the procedure. It was then applied on a study group composed of 302 MCI subjects, 136 having progressed to clinically probable AD (MCI-converters) and 166 having remained stable or recovered to normal condition after a 24month follow-up (MCI-non converters). All subjects came from the ADNI database. METHODS We sampled the brain with 7 relatively small volumes, mainly centered on the MTL, and 2 control regions. These volumes were filtered to give intensity and textural MRI-based features. Each filtered region was analyzed with a Random Forest (RF) classifier to extract relevant features, which were subsequently processed with a Support Vector Machine (SVM) classifier. Once a prediction model was trained and tested on the reference group, it was used to compute a classification index (CI) on the MCI cohort and to assess its accuracy in predicting AD conversion in MCI patients. The performance of the classification based on the features extracted by the whole 9 volumes is compared with that derived from each single volume. All experiments were performed using a bootstrap sampling estimation, and classifier performance was cross-validated with a 20-fold paradigm. RESULTS We identified a restricted set of image features correlated with the conversion to AD. It is shown that most information originate from a small subset of the total available features, and that it is enough to give a reliable assessment. We found multiple, highly localized image-based features which alone are responsible for the overall clinical diagnosis and prognosis. The classification index is able to discriminate Controls from AD with an Area Under Curve (AUC)=0.97 (sensitivity ≃89% at specificity ≃94%) and Controls from MCI-converters with an AUC=0.92 (sensitivity ≃89% at specificity ≃80%). MCI-converters are separated from MCI-non converters with AUC=0.74(sensitivity ≃72% at specificity ≃65%). FINDINGS The present automated MRI-based technique revealed a strong relationship between highly localized baseline-MRI features and the baseline clinical assessment. In addition, the classification index was also used to predict the probability of AD conversion within a time frame of two years. The definition of a single index combining local analysis of several regions can be useful to detect AD neurodegeneration in a typical MCI population.

Automatic analysis of medial temporal lobe atrophy from structural MRIs for the early assessment of Alzheimer disease.

The purpose of this study is to develop a software for the extraction of the hippocampus and surrounding medial temporal lobe (MTL) regions from T1-weighted magnetic resonance (MR) images with no interactive input from the user, to introduce a novel statistical indicator, computed on the intensities in the automatically extracted MTL regions, which measures atrophy, and to evaluate the accuracy of the newly developed intensity-based measure of MTL atrophy to (a) distinguish between patients with Alzheimer disease (AD), patients with amnestic mild cognitive impairment (aMCI), and elderly controls by using established criteria for patients with AD and aMCI as the reference standard and (b) infer about the clinical outcome of aMCI patients. For the development of the software, the study included 61 patients with mild AD (17 men, 44 women; mean age±standard deviation (SD), 75.8years±7.8; Mini Mental State Examination (MMSE) score, 24.1±3.1), 42 patients with aMCI (11 men, 31 women; mean age±SD, 75.2years±4.9; MMSE score, 27.9±1.9), and 30 elderly healthy controls (10 men, 20 women; mean age±SD, 74.7years±5.2; MMSE score, 29.1±0.8). For the evaluation of the statistical indicator, 150 patients with mild AD (62 men, 88 women; mean age±SD, 76.3years±5.8; MMSE score, 23.2±4.1), 247 patients with aMCI (143 men, 104 women; mean age±SD, 75.3years±6.7; MMSE score, 27.0±1.8), and 135 elderly healthy controls (61 men, 74 women; mean age±SD, 76.4years±6.1). Fifty aMCI patients were evaluated every 6 months over a 3 year period to assess conversion to AD. For each participant, two subimages of the MTL regions were automatically extracted from T1-weighted MR images with high spatial resolution. An intensity-based MTL atrophy measure was found to separate control, MCI, and AD cohorts. Group differences wereassessed by using two-sample t test. Individual classification was analyzed by using receiver operating characteristic (ROC) curves. Compared to controls, significant differences in the intensity-based MTL atrophy measure were detected in both groups of patients (AD vs controls, 0.28±0.03 vs 0.34±0.03, P<0.001; aMCI vs controls, 0.31±0.03 vs 0.34±0.03, P<0.001). Moreover, the subgroup of aMCI converters was significantly different from controls (0.27±0.034 vs 0.34±0.03, P<0.001). Regarding the ROC curve for intergroup discrimination, the area under the curve was 0.863 for AD patients vs controls, 0.746 for all aMCI patients vs controls, and 0.880 for aMCI converters vs controls. With specificity set at 85%, the sensitivity was 74% for AD vs controls, 45% for aMCI vs controls, and 83% for aMCI converters vs controls. The automated analysis of MTL atrophy in the segmented volume is applied to the early assessment of AD, leading to the discrimination of aMCI converters with an average 3 year follow-up. This procedure can provide additional useful information in the early diagnosis of AD.

Growth of niobium nitrides by nitrogen-niobium reaction at high temperature

Abstract The reaction between nitrogen and bulk niobium under high purity conditions was studied in the range 1100–1900 °C at 150 kPa. Two different nitride layers are formed: an inner β phase (Nb 2 N) and an outer δ phase (NbN). The latter undergoes a transformation to γ-NbN and ϵ-NbN during cooling down. Nitrogen dissolves in the niobium core forming α solid solution. Both the weight gain and the thickness of the nitride layers follow the parabolic rate law, indicating that the reaction is mainly dominated by diffusional transport through the nitrides. Two parabolic kinetic stages are observed, the first before α phase saturation and the second after saturation. Data analysis based on a multiphase, moving boundary diffusion model allows the calculation of the effective nitrogen diffusion coefficients, yielding the expressions D β = 1.11[±0.5] exp(−3.23[±0.4] × 10 5 /RT) cm 2 s −1 and D δ = 3.27[±1.5] exp(−3.19[±0.25] × 10 5 / RT ) cm 2 s −1 .

Integrating longitudinal information in hippocampal volume measurements for the early detection of Alzheimer's disease.

BACKGROUND Structural MRI measures for monitoring Alzheimers Disease (AD) progression are becoming instrumental in the clinical practice, and more so in the context of longitudinal studies. This investigation addresses the impact of four image analysis approaches on the longitudinal performance of the hippocampal volume. METHODS We present a hippocampal segmentation algorithm and validate it on a gold-standard manual tracing database. We segmented 460 subjects from ADNI, each subject having been scanned twice at baseline, 12-month and 24month follow-up scan (1.5T, T1 MRI). We used the bilateral hippocampal volume v and its variation, measured as the annualized volume change Λ=δv/year(mm(3)/y). Four processing approaches with different complexity are compared to maximize the longitudinal information, and they are tested for cohort discrimination ability. Reference cohorts are Controls vs. Alzheimers Disease (CTRL/AD) and CTRL vs. Mild Cognitive Impairment who subsequently progressed to AD dementia (CTRL/MCI-co). We discuss the conditions on v and the added value of Λ in discriminating subjects. RESULTS The age-corrected bilateral annualized atrophy rate (%/year) were: -1.6 (0.6) for CTRL, -2.2 (1.0) for MCI-nc, -3.2 (1.2) for MCI-co and -4.0 (1.5) for AD. Combined (v, Λ) discrimination ability gave an Area under the ROC curve (auc)=0.93 for CTRL vs AD and auc=0.88 for CTRL vs MCI-co. CONCLUSIONS Longitudinal volume measurements can provide meaningful clinical insight and added value with respect to the baseline provided the analysis procedure embeds the longitudinal information.

Nitridation of niobium-46 wt.% titanium alloy in nitrogen at 1300 °C

Abstract The nitridation of niobium-46 wt.% titanium alloy (βTi-Nb) was studied at 1300 °C in 15 kPa nitrogen under high purity conditions for times ranging from 0.5 to 52 h. Three different reaction layers were observed: (i) an outer, thin continuous layer of superconducting (Nb,Ti)N with f.c.c. structure; (ii) an intermediate, duplex layer formed by hexagonal Nb 2 N containing platelets of TiN; (iii) an inner duplex layer formed by the growth of TiN needles into the titanium-depleted βTi-Nb alloy. The observed microstructure is dominated by the different thermodynamic stability of the nitrides existing in the present conditions; in particular Ti is preferentially nitrided at the interior of the alloy. The TiN needles have the tendency to grow with linear kinetics and to form ordered patterns in the alloy; as a consequence TiN segregation can be tentatively described as a cooperative steady state process. The maximum value of T c , measured from the variation of a.c. susceptibility with temperature, was 17.9 K after 24 h reaction; at longer times a plateau is reached.

Automatic temporal lobe atrophy assessment in prodromal AD: Data from the DESCRIPA study

In the framework of the clinical validation of research tools, this investigation presents a validation study of an automatic medial temporal lobe atrophy measure that is applied to a naturalistic population sampled from memory clinic patients across Europe.

Optical properties of uniform, porous, amorphous Ta2O5 coatings on silica: temperature effects

We present spectroscopic ellipsometry (SE) results, in the 0.75–5 eV spectral range, obtained on highly uniform Ta2O5 coatings deposited on high-quality silica substrates by ion sputtering. The study was motivated mainly by issues related to the exploitation of Ta2O5–SiO2 λ/4 multilayers in detectors of gravitational waves. Two sets of samples with nominal thicknesses of 40 and 500 nm were considered. A sub-set of samples was treated with post-growth annealing in air for several hours at temperatures Tann up to 600 °C. The SE data were complemented with photothermal common-path interferometry measurements at 1064 nm providing data about absorption losses in the 1–4 ppm range. SE data, taken at room temperature, were analysed by exploiting three different three-phase (substrate/film/surface) models (Cody–Lorentz, Tauc–Lorentz and Herzinger–Johs) of the fundamental absorption edge. Following the literature (Stenzel 2009 J. Phys. D: Appl. Phys. 42 055312) the simulations exploited a graded nano-porosity inside the coating, testing both the shape and composition of the pores. The best simulation of data was obtained using the Cody–Lorentz approach and a quasi-uniform density (6–7.5%) of empty spherical pores, slowly degrading from the substrate/film interface towards the film/ambient interface. A comparison with the literature indicated a high stoichiometric quality of the coatings. The analysis of samples annealed to increasingly higher Tann showed (i) a slight blue-shift of the energy gap (ii) an increase in the pore volume fraction, (iii) an increase (1–2%) in the coating thickness, (iv) a small (less than 1%) reduction in the index of refraction in the transparency region and (v) a limited increase in absorption losses. These findings were interpreted in terms of a release of the compressive strain inherent to the deposition process.

First joint gravitational wave search by the AURIGA-EXPLORER-NAUTILUS-Virgo Collaboration

We present a methodology of network data analysis applied to the search for coincident burst excitations over a 24 h long data set collected by AURIGA, EXPLORER, NAUTILUS and Virgo detectors during September 2005. The search of candidate triggers was performed independently on each of the data sets from single detectors. We looked for two-fold time coincidences between these candidates using an algorithm optimized for a given population of sources and we calculated the efficiency of detection through injections of templated signal waveforms into the streams of data. To this end we have considered the case of signals shaped as damped sinusoids coming from the galactic center direction. Our method targets an optimal balance between high efficiency and low false alarm rate, aiming at setting confidence intervals as stringent as possible in terms of the rate of the selected source models.

rf surface resistance measurements of binary and ternary niobium compounds

The superconducting properties of binary and ternary niobium compounds for rf applications are investigated. The materials under study are niobium nitride (NbN), niobium‐titanium nitride (NbTiN), and niobium tin (Nb3Sn). Preparation techniques of the compounds are discussed. NbN and NbTiN are obtained by thermal reaction of bulk Nb in nitrogen atmosphere. Nb3Sn has been obtained using a technique originally developed for high‐field magnet fabrication and modified to be applied to rf cavity production. The experimental apparatus and measurement technique are described. In particular the raw experimental data have been carefully analyzed to obtain important informations on fundamental material parameters. The effect of field penetration in the superconductor and the influence on the experimental results of the normal metallic substrate on which the superconductor is grown is also considered. The measurements show that NbN and Nb3Sn are effectively potentially good materials for rf applications due to their ...

Preparation and characterization of YBa2Cu3O7-x superconducting films deposited by electrophoresis

Abstract The coatings of YBCO superconducting materials deposited on various shapes of silver substrates, by using an electrophoretic technique, have been studied and the effect of several parameters involved in the process has also been discussed. The experimental results show the importance of the milling treatment of the powders before the electrophoretic process. It is found that no deposition could be obtained without an adequate milling procedure to the powders. A series of deposition processes under various conditions with two different kinds of powders, prepared using the standard solid-state reaction method and the pyrolytic method, have shown that the successful deposition of the YBCO films is related to the electrical changing of the powder grains during the milling process. After deposition and thermal treatment the samples are characterized using X-ray diffraction, DC resistive measurements, AC susceptibility measurements. The performances of the films at RF fields are also investigated.