Gradient-based generation of intermediate images for heterogeneous tumor segmentation within hybrid PET/MRI scans.

Segmentation of tumors from hybrid PET/MRI scans plays an essential role in accurate diagnosis and treatment planning. However, when treating tumors, several challenges, notably heterogeneity and the problem of leaking into surrounding tissues with similar high uptake, have to be considered. To address these issues, we propose an automated method for accurate delineation of tumors in hybrid PET/MRI scans. The method is mainly based on creating intermediate images. In fact, an automatic detection technique that determines a preliminary Interesting Uptake Region (IUR) is firstly performed. To overcome the leakage problem, a separation technique is adopted to generate the final IUR. Then, smart seeds are provided for the Graph Cut (GC) technique to obtain the tumor map. To create intermediate images that tend to reduce heterogeneity faced on the original images, the tumor map gradient is combined with the gradient image. Lastly, segmentation based on the GCsummax technique is applied to the generated images. The proposed method has been validated on PET phantoms as well as on real-world PET/MRI scans of prostate, liver and pancreatic tumors. Experimental comparison revealed the superiority of the proposed method over state-of-the-art methods. This confirms the crucial role of automatically creating intermediate images in addressing the problem of wrongly estimating arc weights for heterogeneous targets.

Bayesian phylogenetic analysis of the influenza-A virus genomes isolated in Tunisia, and determination of potential recombination events.

The influenza-A virus (IAV) causes seasonal epidemics and presents a pandemic risk with the possibility of genetic re-assortment, allowing the emergence of new strains. The evolution of IAVes is done most often by relatively frequent re-assortment between gene segments, but the hypothesis of their evolution by recombination between RNA segments has not been justified to this date. Here, we examine this hypothesis by Bayesian phylogenetic analysis, to test if recombination events have occurred between genomic RNA segments. Different IAV subtypes are observed in co-circulation in Tunisia, which increases the probability of occurrence of double infections. Mixed infections are a prerequisite for recombination between co-infecting of viral strains. The aim of this work, and since understanding the evolutionary dynamics of IAV is essential for controlling human and avian influenza, phylogenetic analyzes (Bayesian approach) have been carried out for IAV strains isolated in Tunisia, to study their co-evolutionary history, trends, and possible recombination models. A set of IAV nucleic sequences, isolated in Tunisia from 2009 to 2013 (n = 102) were used in this study. These genomic segments encode various influenza A proteins. These viral strains studied were isolated following the 2009 H1N1 pandemic. The analyzes identified two large distinct groups of viral sequences and different subgroups. Assuming a relaxed molecular clock model (uncorrelated exponential (uced)) in a Bayesian coalescence approach and a constant effective time demographic history model (Coalescent: constant size), the substitution rate was estimated at 1.356 × 10-3 substitutions/site/year for segment 4 (haemagglutinin HA gene). Consistent estimates of the age of the most recent Common Ancestor (MRCA) were obtained for the different subgroups, the MRCA ages of the two viral populations corresponding to segment 4 and segment 6 (neuraminidase gene NA) of the genome are estimated at 443.737 years and 501.159 years respectively. A detailed phylogenetic study of the HA gene was performed. The incongruous phylogenetic models deduced for the three genomic subgroups studied corresponding to this gene were indicative of recombination events between the different subpopulations. The detection of these relative signals indicating the presence of recombination events can be considered as proof that recombination seems to play a role, even a small one, in the evolution of (IAV). Reliable recombination sites have been located with statistical significance between H3, H1 and H9 subtypes. MRCA age estimates of recombinants phylogenetic clades indicate directional gene transfers from the H1 and H9 populations to the H3 population, and from H1 and H3 to the H9 population, and their co-divergences during the study period.

Hybrid PET/MRI co-segmentation based on joint fuzzy connectedness and graph cut.

BACKGROUND AND OBJECTIVE: Tumor segmentation from hybrid PET/MRI scans may be highly beneficial in radiotherapy treatment planning. Indeed, it gives for both modalities the suitable information that could make the delineation of tumors more accurate than using each one apart. We aim in this work to propose a co-segmentation method that deals with several challenges, notably the lack of one-to-one correspondence between tumors of the two modalities and the boundaries' smoothing. METHODS: The proposed method is designed to surpass these limits, we propose a segmentation method based on the GCsummax technique. The method takes the advantage of Iterative Relative Fuzzy Connectedness (IRFC) on seeds initialization, and the standard min-cut/max-flow technique for the boundary smoothing. Seed initialization was accurately performed thanks to high uptake regions on PET. Besides, a visibility weighting scheme was adapted to achieve the task of co-segmentation using the IRFC algorithm. Then, given the co-segmented regions, we introduce a morphological-based technique that provides object seeds to standard Graph Cut (GC) allowing it to avoid the shrinking problem. Finally, for each modality, the segmentation task is formulated as an energy minimization problem which is resolved by a min-cut/max-flow technique. RESULTS: The overlap ratio (denoted DSC) between our segmentation results and the ground-truth for PET images is 92.63  ±â€¯ 1.03, while the DSC for MRI images is 90.61  ±â€¯ 3.70. CONCLUSIONS: The proposed method was tested on different types of diseases and it outperformed the state-of-the-art methods. We show its superiority in terms of assymetric relation between PET and MRI and tumors heterogeneity.

[Not Available]. / Les recherches d'Étienne Burnet (1920-1928) sur la brucellose.

Mediterranean fever or brucellosis was an endemic disease at the beginning of the 20th century in the Mediterranean area. Étienne Burnet, a pastorian researcher, studied this zoonosis in the Pasteur Institute of Tunis between 1920 and 1928 and enhanced our knowledge with various experiences on the genius Brucella, particularly melitensis variety. He developed the so-called Burnet's test or melitine IDR diagnose test. The thermo-agglutination of paramelitensis group, now known as the S forms colonies, led him question the variability of this non-specific character. He showed that thermo-agglutination is associated with specific antigenic properties and is common with other bacteria's species and could be acquired cross over colonies culture... The authors attempt to reconstitute the context of these experiences and to show the actuality of evolutionary Burnet's conception of living micro-organisms.

Angiogenic activity in the sera of patients with post-kidney transplant erythrocytosis.

Post-kidney transplant erythrocytosis (PTE) is one of the hematological complications in the renal transplant patients. While its pathogenesis still remains to be elucidated completely, a number of therapies are available for the management of PTE. The aim of this prospective study was to investigate whether angiogenesis may be involved in the pathogenesis of post-transplant erythrocytosis by comparing its level with those of different classes of erythrocytosis [polycythemia vera (PV), idiopathic erythrocytosis and secondary erythrocytosis]. The angiogenic activity was evaluated by the assessment of the serum vascular endothelial growth factor (VEGF) levels, as one of circulating angiogenic factor, using a standardized enzyme-linked immunosorbent assay commercial kit in 13 PTE (2 F/11 M), in 75 untreated erythrocytosis non-transplant patients and in 21 healthy subjects controls. The results indicated that VEGF was overproduced in advanced and untreated PV patients and to a lesser degree in idiopathic erythrocytosis thus confirming an increased angiogenic activity. However, there is no evidence of increased angiogenesis in PTE and in secondary erythrocytosis. The absence of angiogenesis in PTE and its presence in PV is another argument that the pathogenesis of these two entities is different.

Genetic heterogeneity of megaloblastic anaemia type 1 in Tunisian patients.

Megaloblastic anaemia 1 (MGA1) is a rare autosomal recessive condition characterized by selective intestinal vitamin B12 malabsorption and proteinuria. More than 200 MGA1 patients have been identified worldwide, but the disease is relatively prevalent in Finland, Norway and several Eastern Mediterranean regions. MGA1 is genetically heterogeneous and can be caused by mutations in either the cubilin (CUBN) or the amnionless (AMN) gene. In the present study we investigated the molecular defect underlying MGA1 in nine Tunisian patients belonging to six unrelated consanguineous families. Haplotype and linkage analyses, using microsatellite markers surrounding both CUBN and AMN genes, indicated that four out of the six families were likely to be linked to the CUBN gene. Patients from these families were screened for the Finnish, Mediterranean and Arabian mutations already published. None of the screened mutations could be detected in our population. One family showed a linkage to AMN gene. Direct screening of the AMN gene allowed the identification of the c.208-2A>G mutation, previously described in a Jewish Israeli patient of Tunisian origin and in Turkish patients. This suggests that the c.208-2A>G mutation may derive from a single Mediterranean founder ancestor. For the last family, haplotype analysis excluded both CUBN and AMN genes, suggesting the existence of a third locus that may cause MGA1.

Megaloblastic anemia in North Africa.

We prospectively studied 478 patients with megaloblastic anemia living in Tunisia. Overall, 98% of patients had vitamin B12 deficiency. Pernicious anemia accounted for most of these cases, and median age at presentation was 45 years. Megaloblastic anemia occurred in 19 subjects under 15 years of age, and of these, nine had the Immerslund-Graesbeck syndrome.