Publications

The genetic risk factors for chronic obstructive pulmonary disease (COPD) are still largely unknown. To date, genome-wide association studies (GWASs) of limited size have identified several novel risk loci for COPD at CHRNA3/CHRNA5/IREB2, HHIP and FAM13A; additional loci may be identified through larger studies. We performed a GWAS using a total of 3499 cases and 1922 control subjects from four cohorts: the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE); the Normative Aging Study (NAS) and National Emphysema Treatment Trial (NETT); Bergen, Norway (GenKOLS); and the COPDGene study. Genotyping was performed on Illumina platforms with additional markers imputed using 1000 Genomes data; results were summarized using fixed-effect meta-analysis. We identified a new genome-wide significant locus on chromosome 19q13 (rs7937, OR = 0.74, P = 2.9 × 10(-9)). Genotyping this single nucleotide polymorphism (SNP) and another nearby SNP in linkage disequilibrium (rs2604894) in 2859 subjects from the family-based International COPD Genetics Network study (ICGN) demonstrated supportive evidence for association for COPD (P = 0.28 and 0.11 for rs7937 and rs2604894), pre-bronchodilator FEV(1) (P = 0.08 and 0.04) and severe (GOLD 3&4) COPD (P = 0.09 and 0.017). This region includes RAB4B, EGLN2, MIA and CYP2A6, and has previously been identified in association with cigarette smoking behavior.

The nonlocal means (NLM) filter has become a popular approach for denoising medical images due to its excellent performance. However, its heavy computational load has been an important shortcoming preventing its use. NLM works by averaging pixels in nonlocal vicinities, weighting them depending on their similarity with the pixel of interest. This similarity is assessed based on the squared difference between corresponding pixels inside local patches centered at the locations compared. Our proposal is to reduce the computational load of this comparison by checking only a subset of salient features associated to the pixels, which suffice to estimate the actual difference as computed in the original NLM approach. The speedup achieved with respect to the original implementation is over one order of magnitude, and, when compared to more recent NLM improvements for MRI denoising, our method is nearly twice as fast. At the same time, we evidence from both synthetic and in vivo experiments that computing of appropriate salient features make the estimation of NLM weights more robust to noise. Consequently, we are able to improve the outcomes achieved with recent state of the art techniques for a wide range of realistic Signal-to-Noise ratio scenarios like diffusion MRI. Finally, the statistical characterization of the features computed allows to get rid of some of the heuristics commonly used for parameter tuning.

Least Squares (LS) and its minimum variance counterpart, Weighted Least Squares (WLS), have become very popular when estimating the Diffusion Tensor (DT), to the point that they are the standard in most of the existing software for diffusion MRI. They are based on the linearization of the Stejskal-Tanner equation by means of the logarithmic compression of the diffusion signal. Due to the Rician nature of noise in traditional systems, a certain bias in the estimation is known to exist. This artifact has been made patent through some experimental set-ups, but it is not clear how the distortion translates in the reconstructed DT, and how important it is when compared to the other source of error contributing to the Mean Squared Error (MSE) in the estimate, i.e. the variance. In this paper we propose the analytical characterization of log-Rician noise and its propagation to the components of the DT through power series expansions. We conclude that even in highly noisy scenarios the bias for log-Rician signals remains moderate when compared to the corresponding variance. Yet, with the advent of Parallel Imaging (pMRI), the Rician model is not always valid. We make our analysis extensive to a number of modern acquisition techniques through the study of a more general Non Central-Chi (nc-χ) model. Since WLS techniques were initially designed bearing in mind Rician noise, it is not clear whether or not they still apply to pMRI. An important finding in our work is that the common implementation of WLS is nearly optimal when nc-χ noise is considered. Unfortunately, the bias in the estimation becomes far more important in this case, to the point that it may nearly overwhelm the variance in given situations. Furthermore, we evidence that such bias cannot be removed by increasing the number of acquired gradient directions. A number of experiments have been conducted that corroborate our analytical findings, while in vivo data have been used to test the actual relevance of the bias in the estimation.

Inferring on the geometry of an object from its frequency spectrum is highly appealing since the object could then be imaged noninvasively or from a distance (as famously put by Kac, "can one hear the shape of a drum?"). In nuclear magnetic resonance of porous systems, the shape of the drum is represented by the pore density function that bears all the information on the collective pore microstructure. So far, conventional magnetic resonance imaging (MRI) could only detect the pore autocorrelation function, which inherently obscures fine details on the pore structure. Here, for the first time, we report on a unique imaging mechanism arising from synergistic diffusion-diffractions that directly yields the pore density function. This mechanism offers substantially higher spatial resolution compared to conventional MRI while retaining all fine details on the collective pore morphology. Thus, using these unique synergistic diffusion-diffractions, the "shape of the drum" can be inferred.

Diffusion Tensor Imaging (DTI) tractography and functional Magnetic Resonance Imaging (fMRI) investigate two complementary aspects of brain networks: white matter (WM) anatomical connectivity and gray matter (GM) function. However, integration standards have yet to be defined; namely, individual fMRI-driven tractography is usually applied and only few studies address group analysis. This work proposes an efficient method of fMRI-driven tractography at group level through the creation of a tractographic atlas starting from the GM areas activated by a verbal fluency task in 11 healthy subjects. The individual tracts were registered to the MNI space. Selection ROIs derived by GM masking and dilation of group activated areas were applied to obtain the fMRI-driven subsets within tracts. An atlas of the tracts recruited among the population was obtained by selecting for each subject the fMRI-guided tracts passing through the high probability voxels (the voxels recruited by the 90% of the subjects) and merging them together. The reliability of this approach was assessed by comparing it with the probabilistic atlas previously introduced in literature. The introduced method allowed to successfully reconstruct activated tracts, which comprehended corpus callosum, left cingulum and arcuate, a small portion of the right arcuate, both cortico-spinal tracts and inferior fronto-occipital fasciculi. Moreover, it proved to give results concordant with the previously introduced probabilistic approach, allowing in addition to reconstruct 3D trajectories of the activated fibers, which appear particularly helpful in the detection of WM connections.

We formulate the pigmented-skin-lesion (PSL) matching problem as a relaxed labeling of an association graph. In this graph labeling problem, each node represents a mapping between a PSL from one image to a PSL in the second image and the optimal labels are those optimizing a high order Markov Random Field energy (MRF). The energy is made up of unary, binary, and ternary energy terms capturing the likelihood of matching between the points, edges, and cliques of two graphs representing the spatial distribution of the two PSL sets. Following an exploration of various MRF energy terms, we propose a novel entropy energy term encouraging solutions with low uncertainty. By interpreting the relaxed labeling as a measure of confidence, we further leverage the high confidence matching to sequentially constrain the learnt objective function defined on the association graph. We evaluate our method on a large set of synthetic data as well as 56 pairs of real dermatological images. Our proposed method compares favorably with the state-of-the-art.

Chemokine (C-C motif) receptor 2 (CCR2)-signaling can mediate accumulation of microglia at sites affected by neuroinflammation. CCR2 and its main ligand CCL2 (MCP-1) might also be involved in the altered metabolism of beta-amyloid (Aβ) underlying Alzheimer’s disease (AD). We therefore measured the levels of CCL2 and three other CCR2 ligands, i.e. CCL11 (eotaxin), CCL13 (MCP-4) and CCL26 (eotaxin-3), in the cerebrospinal fluid (CSF) and plasma of 30 controls and 119 patients with mild cognitive impairment (MCI) at baseline. During clinical follow-up 52 MCI patients were clinically stable for five years, 47 developed AD (i.e. cases with prodromal AD at baseline) and 20 developed other dementias. Only CSF CCL26 was statistically significantly elevated in patients with prodromal AD when compared to controls (p = 0.002). However, in patients with prodromal AD, the CCL2 levels in CSF at baseline correlated with a faster cognitive decline during follow-up (r(s) = 0.42, p = 0.004). Furthermore, prodromal AD patients in the highest tertile of CSF CCL2 exhibited a significantly faster cognitive decline (p

We propose a novel approach to identify the foci of a neurological disorder based on anatomical and functional connectivity information. Specifically, we formulate a generative model that characterizes the network of abnormal functional connectivity emanating from the affected foci. We employ the variational EM algorithm to fit the model and to identify both the afflicted regions and the differences in connectivity induced by the disorder. We demonstrate our method on a population study of schizophrenia.

In the title compound, C(14)H(18)O(6), a crystallographic center at the centroid of the aromatic ring generates the complete mol-ecule which is planar within 0.085 (1) Å for the non-H atoms. In the crystal, weak C-H...O and C-H...π inter-actions link the molecules.