A novel approach to error function minimization for feedforward neural networks

Feedforward neural networks with error backpropagation (FFBP) are widely applied to pattern recognition. One general problem encountered with this type of neural networks is the uncertainty, whether the minimization procedure has converged to a global minimum of the cost function. To overcome this problem a novel approach to minimize the error function is presented. It allows to monitor the approach to the global minimum and as an outcome several ambiguities related to the choice of free parameters of the minimization procedure are removed.Comment: 11 pages, latex, 3 figures appended as uuencoded fil

Neural Network based Electron Identification in the ZEUS Calorimeter

We present an electron identification algorithm based on a neural network approach applied to the ZEUS uranium calorimeter. The study is motivated by the need to select deep inelastic, neutral current, electron proton interactions characterized by the presence of a scattered electron in the final state. The performance of the algorithm is compared to an electron identification method based on a classical probabilistic approach. By means of a principle component analysis the improvement in the performance is traced back to the number of variables used in the neural network approach.Comment: 20 pages, latex, 16 figures appended as uuencoded fil

Elastographie-IRM pour le diagnostic et la caractérisation des lésions du sein

L élastographie-IRM du sein (MRE) est une technique d imagerie fonctionnelle non invasive utilisant les propriétés visco-élastiques des tissus et qui permet comme en élastographie-échographie d évaluer la rigidité d une lésion. Il est également possible, à la différence de l élastographie-échographie, d évaluer le degré de viscosité d une lésion, et ainsi grâce à la combinaison élasticité/viscosité, comparée à l analyse des paramètres IRM classiques comme la morphologie ou la cinétique de rehaussement, d améliorer la caractérisation lésionnelle. Très peu d études en élastographie-IRM du sein ont été menées à ce jour, essentiellement du fait d une problématique instrumentale et de mise à disposition d une antenne dédiée sein équipé d un dispositif de génération des ondes de cisaillement dans le sein. Dans un premier temps, nous avons pu établir et optimiser une séquence élasto-IRM du sein sur une série de 10 volontaires saines. Cette séquence basée sur un principe de séquence Spin Echo EPI-MRE 3D, a permis l acquisition de 50 coupes en 10 minutes sur un sein, compatible avec la pratique clinique en IRM du sein. Une approche multifréquence à 37,5 Hz, 75 Hz et 112,5 Hz a été ensuite testée sur les trois dernières volontaires puis transférées à notre population de patientes. Cette séquence multifréquence permettait la continuité de diffusion des ondes dans le sein. 50 patientes présentant des lésions indéterminées ou suspectes du sein (37 cancers, 13 bénins) ont ensuite été incluses dans ce protocole et examinées par IRM du sein classique avec séquence supplémentaire élasto-IRM. Certaines patientes étaient aussi examinées en élasto-échographie. Les données IRM morphologiques, dynamiques et de visco-élasticité IRM ont été corrélées à l histologie. Nous avons pu montrer que les paramètres visco-élastiques IRM étaient fortement corrélés avec le score de malignité d une lésion (Bi-RADS ACR) et avec le caractère différentiel bénin/malin. C est notamment le paramètre Gd qui représente l élasticité, qui était plus faible en cas de lésion suspecte BI-RADS 5. Le paramètre Gl était plus élevé dans les lésions malignes par rapport aux lésions bénignes, avec un niveau de viscosité statistiquement supérieur dans les lésions malignes. Le meilleur paramètre semble être le rapport y (Gl/Gd) qui était aussi significativement élevé dans les lésions malignes par comparaison avec les lésions bénignes du sein, et qui a été analysé comme un facteur indépendant. En pratique, l ajout de la séquence MRE à un examen IRM du sein classique a permis dans notre étude d améliorer significativement la sensibilité de l IRM (de 78 à 91 %) sans perte de spécificité, celle-ci étant initialement très bonne dans cette étude. Nous n avons pas en revanche établi de lien entre la fibrose, la quantification vasculaire ou la nécrose pour expliquer ces phénomènes de visco-élasticité des tumeurs. En conclusion, l élasto-IRM peut s avérer utile pour améliorer le diagnostic de lésions du sein en IRM. Une poursuite des travaux avec optimisation de la séquence pour qu elle puisse permettre l analyse des deux seins sera nécessaire pour sa diffusion en pratique clinique. Ce travail pourrait idéalement se poursuivre sur une plus grande série de patientes.MR-elastography (MRE) is a non-invasive functional Imaging technique using tissue mechanical visco-elastic properties to evaluate tissue stifness. MRE is different from elasticity Imaging in ultrasound, as it is possible to evaluate tumour viscosity. Combining viscosity and elasticity may improve MRI accuracy, in comparison with classical morphological and kinetics criteria. Only very few studies are focused on breast MRE, because of low availability of dedicated breast coils with MRE devices. Firstly, we developed and optimized a breast MRE sequence on a population of 10 volunteers. This sequence is based on a Spin Echo EPI-MRE 3D, and it was possible to acquire 50 slices on one breast in 10 minutes, which is applicable in a clinical routine in breast MRI. Secondly, a multi-frequency approach 37,5 Hz, 75 Hz and 112,5 Hz has been evaluated on the last three volunteers, then transferred to our patient s population. A continous diffusion of waves within the breast was possible with this multifrequency approach sequence. 50 patients presenting undetermined or suspicious breast lesions (37 cancers, 13 benign lesions) were included in this study and examined with a standard breast MRI and MRE sequence. Some patients were also examined with shear-wave ultrasound elastography (ARFI mode, Siemens ®). Morphological, kinetic and visco-elastic MR parameters were correlated to pathology. We demonstrated that MR visco-elastic properties were strongly correlated with Bi-RADS ACR malignancy score of a breast lesion and with malignant and benign status. The best parameter was Gd (dynamic modulus), which corresponded to lesion stiffness. Gd was lower in case of BI-RADS 5 lesions. Gl parameter (Loss modulus) was higher in malignant lesions in comparison with benign lesions, with viscosity level statistically higher in malignant lesions. The best criterion was the ratio y (Gl/Gd), which was significantly higher in malignant lesions in comparison with benign lesions; ratio y was statistically an independent factor. In practice, addition of a MRE sequence to a standard breast MRI improved significantly breast MRI Sensitity (78 to 91 %) without reduction in specificity; Sp was anyway initially high in our study. Nevertheless, we didn t demonstrate a statistical correlation with fibrosis, vascular grading or necrosis with MRE parameters, to explain visco-elastic properties of breast tumours. In conclusion, MR-elastography may be useful to improve breast MRI accuracy. In future studies, MRE sequence may be optimized to allow a bilateral acquisition on both breasts, which would be useful in clinical practice. Future works could include higher number of patients to confirm our results.PARIS11-SCD-Bib. électronique (914719901) / SudocSudocFranceF

Magnetic resonance elastography in nonlinear viscoelastic materials under load.

Characterisation of soft tissue mechanical properties is a topic of increasing interest in translational and clinical research. Magnetic resonance elastography (MRE) has been used in this context to assess the mechanical properties of tissues in vivo noninvasively. Typically, these analyses rely on linear viscoelastic wave equations to assess material properties from measured wave dynamics. However, deformations that occur in some tissues (e.g. liver during respiration, heart during the cardiac cycle, or external compression during a breast exam) can yield loading bias, complicating the interpretation of tissue stiffness from MRE measurements. In this paper, it is shown how combined knowledge of a material's rheology and loading state can be used to eliminate loading bias and enable interpretation of intrinsic (unloaded) stiffness properties. Equations are derived utilising perturbation theory and Cauchy's equations of motion to demonstrate the impact of loading state on periodic steady-state wave behaviour in nonlinear viscoelastic materials. These equations demonstrate how loading bias yields apparent material stiffening, softening and anisotropy. MRE sensitivity to deformation is demonstrated in an experimental phantom, showing a loading bias of up to twofold. From an unbiased stiffness of [Formula: see text] Pa in unloaded state, the biased stiffness increases to 9767.5 [Formula: see text]1949.9 Pa under a load of [Formula: see text] 34% uniaxial compression. Integrating knowledge of phantom loading and rheology into a novel MRE reconstruction, it is shown that it is possible to characterise intrinsic material characteristics, eliminating the loading bias from MRE data. The framework introduced and demonstrated in phantoms illustrates a pathway that can be translated and applied to MRE in complex deforming tissues. This would contribute to a better assessment of material properties in soft tissues employing elastography

Thymidine Metabolism as Confounding Factor of 3'-Deoxy-3'-[18F]Fluorothymidine Uptake after Therapy in a Colorectal Cancer Model.

Non-invasive monitoring of tumor therapy response helps in developing personalized treatment strategies. Here, we performed sequential positron emission tomography (PET) and diffusion-weighted magnetic resonance imaging (DW-MRI) to evaluate changes induced by a FOLFOX-like combination chemotherapy in colorectal cancer (CRC) xenografts, to identify the cellular and molecular determinants of these imaging biomarkers. Methods: Tumor bearing CD1 nude mice, engrafted with FOLFOX-sensitive Colo205 CRC xenografts, were treated with FOLFOX (5 fluorouracil, leucovorin and oxaliplatin) in weekly intervals. On d1, d2, d6, d9 and d13 of therapy, tumors were assessed by in vivo imaging and ex vivo analyses. In addition, HCT116 xenografts, which did not respond to the FOLFOX treatment, were imaged on d1 of therapy. Results: In Colo205 xenografts, FOLFOX induced a profound increase in uptake of the proliferation PET tracer 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT), which was accompanied by increases in markers for proliferation (Ki67, TK1) and for activated DNA damage response (DDR; γH2AX), whereas the effect on cell death was minimal. As tracer uptake was unaltered in the HCT116 model, these changes appear to be specific for tumor response. Conclusion: We demonstrate that [18F]FLT PET can non-invasively monitor molecular alterations induced by a cancer treatment, including thymidine metabolism and DDR. The cellular or imaging changes may not, however, be directly related to therapy response as assessed by volumetric measurements

Finite element analysis of normal pressure hydrocephalus: influence of CSF content and anisotropy in permeability

Hydrocephalus is a cerebral disease where brain ventricles enlarge and compress the brain parenchyma towards the skull leading to symptoms like dementia, walking disorder and incontinence. The origin of normal pressure hydrocephalus is still obscure. In order to study this disease, a finite element model is built using the geometries of the ventricles and the skull measured by magnetic resonance imaging. The brain parenchyma is modelled as a porous medium fully saturated with cerebrospinal fluid (CSF) using Biot’s theory of consolidation (1941). Owing to the existence of bundles of axons, the brain parenchyma shows locally anisotropic behaviour. Indeed, permeability is higher along the fibre tracts in the white matter region. In contrast, grey matter is isotropic. Diffusion tensor imaging is used to establish the local CSF content and the fibre tracts direction together with the associated local frame where the permeability coefficients are given by dedicated formulas. The present study shows that both inhomogeneous CSF content and anisotropy in permeability have a great influence on the CSF flow pattern through the parenchyma under an imposed pressure gradient between the ventricles and the subarachnoid spaces

Gene expression signature of cerebellar hypoplasia in a mouse model of Down syndrome during postnatal development

Background Down syndrome is a chromosomal disorder caused by the presence of three copies of chromosome 21. The mechanisms by which this aneuploidy produces the complex and variable phenotype observed in people with Down syndrome are still under discussion. Recent studies have demonstrated an increased transcript level of the three-copy genes with some dosage compensation or amplification for a subset of them. The impact of this gene dosage effect on the whole transcriptome is still debated and longitudinal studies assessing the variability among samples, tissues and developmental stages are needed. Results We thus designed a large scale gene expression study in mice (the Ts1Cje Down syndrome mouse model) in which we could measure the effects of trisomy 21 on a large number of samples (74 in total) in a tissue that is affected in Down syndrome (the cerebellum) and where we could quantify the defect during postnatal development in order to correlate gene expression changes to the phenotype observed. Statistical analysis of microarray data revealed a major gene dosage effect: for the three-copy genes as well as for a 2 Mb segment from mouse chromosome 12 that we show for the first time as being deleted in the Ts1Cje mice. This gene dosage effect impacts moderately on the expression of euploid genes (2.4 to 7.5% differentially expressed). Only 13 genes were significantly dysregulated in Ts1Cje mice at all four postnatal development stages studied from birth to 10 days after birth, and among them are 6 three-copy genes. The decrease in granule cell proliferation demonstrated in newborn Ts1Cje cerebellum was correlated with a major gene dosage effect on the transcriptome in dissected cerebellar external granule cell layer. Conclusion High throughput gene expression analysis in the cerebellum of a large number of samples of Ts1Cje and euploid mice has revealed a prevailing gene dosage effect on triplicated genes. Moreover using an enriched cell population that is thought responsible for the cerebellar hypoplasia in Down syndrome, a global destabilization of gene expression was not detected. Altogether these results strongly suggest that the three-copy genes are directly responsible for the phenotype present in cerebellum. We provide here a short list of candidate genes

Response Monitoring with [18F]FLT PET and Diffusion-Weighted MRI After Cytotoxic 5-FU Treatment in an Experimental Rat Model for Colorectal Liver Metastases.

PURPOSE: The aim of the study was to investigate the potential of diffusion-weighted magnetic resonance imaging (DW-MRI) and 3'-dexoy-3'-[(¹⁸)F]fluorothymidine ([(¹⁸)F]FLT) positron emission tomography (PET) as early biomarkers of treatment response of 5-fluorouracil (5-FU) in a syngeneic rat model of colorectal cancer liver metastases. PROCEDURES: Wag/Rij rats with intrahepatic syngeneic CC531 tumors were treated with 5-FU (15, 30, or 60 mg/kg in weekly intervals). Before treatment and at days 1, 3, 7, and 14 after treatment rats underwent DW-MRI and [(¹⁸)F]FLT PET. Tumors were analyzed immunohistochemically for Ki67, TK1, and ENT1 expression. RESULTS: 5-FU inhibited the growth of CC531 tumors in a dose-dependent manner. Immunohistochemical analysis did not show significant changes in Ki67, TK1, and ENT1 expression. However, [(¹⁸)F]FLT SUV_mean and SUV_max were significantly increased at days 4 and 7 after treatment with 5-FU (60 mg/kg) and returned to baseline at day 14 (SUV_max at days -1, 4, 7, and 14 was 1.1 ± 0.1, 2.3 ± 0.5, 2.3 ± 0.6, and 1.5 ± 0.4, respectively). No changes in [(¹⁸)F]FLT uptake were observed in the nontreated animals. Furthermore, the apparent diffusion coefficient (ADCmean) did not change in 5-FU-treated rats compared to untreated rats. CONCLUSION: This study suggests that 5-FU treatment induces a flare in [(¹⁸)F]FLT uptake of responsive CC531 tumors in the liver, while the ADC_mean did not change significantly. Future studies in larger groups are warranted to further investigate whether [(¹⁸)F]FLT PET can discriminate between disease progression and treatment response.The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking (www.imi.europa.eu) under grant agreement number 115151, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution

Response Monitoring with [18F]FLT PET and Diffusion-Weighted MRI After Cytotoxic 5-FU Treatment in an Experimental Rat Model for Colorectal Liver Metastases.

PURPOSE: The aim of the study was to investigate the potential of diffusion-weighted magnetic resonance imaging (DW-MRI) and 3'-dexoy-3'-[18F]fluorothymidine ([18F]FLT) positron emission tomography (PET) as early biomarkers of treatment response of 5-fluorouracil (5-FU) in a syngeneic rat model of colorectal cancer liver metastases. PROCEDURES: Wag/Rij rats with intrahepatic syngeneic CC531 tumors were treated with 5-FU (15, 30, or 60 mg/kg in weekly intervals). Before treatment and at days 1, 3, 7, and 14 after treatment rats underwent DW-MRI and [18F]FLT PET. Tumors were analyzed immunohistochemically for Ki67, TK1, and ENT1 expression. RESULTS: 5-FU inhibited the growth of CC531 tumors in a dose-dependent manner. Immunohistochemical analysis did not show significant changes in Ki67, TK1, and ENT1 expression. However, [18F]FLT SUVmean and SUVmax were significantly increased at days 4 and 7 after treatment with 5-FU (60 mg/kg) and returned to baseline at day 14 (SUVmax at days -1, 4, 7, and 14 was 1.1 ± 0.1, 2.3 ± 0.5, 2.3 ± 0.6, and 1.5 ± 0.4, respectively). No changes in [18F]FLT uptake were observed in the nontreated animals. Furthermore, the apparent diffusion coefficient (ADCmean) did not change in 5-FU-treated rats compared to untreated rats. CONCLUSION: This study suggests that 5-FU treatment induces a flare in [18F]FLT uptake of responsive CC531 tumors in the liver, while the ADCmean did not change significantly. Future studies in larger groups are warranted to further investigate whether [18F]FLT PET can discriminate between disease progression and treatment response.The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking (www.imi.europa.eu) under grant agreement number 115151, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution