Using high-resolution quantitative mapping of R1 as an index of cortical myelination

A fundamental tenet of neuroscience is that cortical functional differentiation is related to the cross-areal differences in cyto-, receptor-, and myeloarchitectonics that are observed in ex-vivo preparations. An ongoing challenge is to create noninvasive magnetic resonance (MR) imaging techniques that offer sufficient resolution, tissue contrast, accuracy and precision to allow for characterization of cortical architecture over an entire living human brain. One exciting development is the advent of fast, high-resolution quantitative mapping of basic MR parameters that reflect cortical myeloarchitecture. Here, we outline some of the theoretical and technical advances underlying this technique, particularly in terms of measuring and correcting for transmit and receive radio frequency field inhomogeneities. We also discuss new directions in analytic techniques, including higher resolution reconstructions of the cortical surface. We then discuss two recent applications of this technique. The first compares individual and group myelin maps to functional retinotopic maps in the same individuals, demonstrating a close relationship between functionally and myeloarchitectonically defined areal boundaries (as well as revealing an interesting disparity in a highly studied visual area). The second combines tonotopic and myeloarchitectonic mapping to localize primary auditory areas in individual healthy adults, using a similar strategy as combined electrophysiological and post-mortem myeloarchitectonic studies in non-human primates.

Empirical antifungal therapy in neutropaenic cancer patients with persistent fever

Invasive fungal infections are frequent and severe complications in leukaemic patients with prolonged neutropaenia. Empirical antifungal therapy has become the standard of care in patients with persistent fever despite treatment with broad-spectrum antibiotics. For decades amphotericin B deoxycholate has been the sole option for empirical antifungal therapy. Recently, several new antifungal agents became available. The choice of the most appropriate drug should be guided by efficacy and safety criteria. The recommendations from the First European Conference on Infections in Leukaemia (ECIL-1) on empirical antifungal therapy in neutropaenic cancer patients with persistent fever have been developed by an expert panel after assessment of clinical practices in Europe and evidence-based review of the literature. Many antifungal regimens can now be recommended for empirical therapy in neutropaenic cancer patients. However, persistent fever lacks specificity for initiation of therapy. Development of empirical and pre-emptive strategies using new clinical parameters, laboratory markers and imaging techniques for early diagnosis of invasive mycoses are needed.

Osteoporotic fracture risk in elderly women: estimation with quantitative heel US and clinical risk factors

PURPOSE: To derive a prediction rule by using prospectively obtained clinical and bone ultrasonographic (US) data to identify elderly women at risk for osteoporotic fractures. MATERIALS AND METHODS: The study was approved by the Swiss Ethics Committee. A prediction rule was computed by using data from a 3-year prospective multicenter study to assess the predictive value of heel-bone quantitative US in 6174 Swiss women aged 70-85 years. A quantitative US device to calculate the stiffness index at the heel was used. Baseline characteristics, known risk factors for osteoporosis and fall, and the quantitative US stiffness index were used to elaborate a predictive rule for osteoporotic fracture. Predictive values were determined by using a univariate Cox model and were adjusted with multivariate analysis. RESULTS: There were five risk factors for the incidence of osteoporotic fracture: older age (>75 years) (P < .001), low heel quantitative US stiffness index (<78%) (P < .001), history of fracture (P = .001), recent fall (P = .001), and a failed chair test (P = .029). The score points assigned to these risk factors were as follows: age, 2 (3 if age > 80 years); low quantitative US stiffness index, 5 (7.5 if stiffness index < 60%); history of fracture, 1; recent fall, 1.5; and failed chair test, 1. The cutoff value to obtain a high sensitivity (90%) was 4.5. With this cutoff, 1464 women were at lower risk (score, <4.5) and 4710 were at higher risk (score, >or=4.5) for fracture. Among the higher-risk women, 6.1% had an osteoporotic fracture, versus 1.8% of women at lower risk. Among the women who had a hip fracture, 90% were in the higher-risk group. CONCLUSION: A prediction rule obtained by using quantitative US stiffness index and four clinical risk factors helped discriminate, with high sensitivity, women at higher versus those at lower risk for osteoporotic fracture.

Objective assessment of image quality in conventional and digital mammography taking into account dynamic range.

The goal of this work is to develop a method to objectively compare the performance of a digital and a screen-film mammography system in terms of image quality. The method takes into account the dynamic range of the image detector, the detection of high and low contrast structures, the visualisation of the images and the observer response. A test object, designed to represent a compressed breast, was constructed from various tissue equivalent materials ranging from purely adipose to purely glandular composition. Different areas within the test object permitted the evaluation of low and high contrast detection, spatial resolution and image noise. All the images (digital and conventional) were captured using a CCD camera to include the visualisation process in the image quality assessment. A mathematical model observer (non-prewhitening matched filter), that calculates the detectability of high and low contrast structures using spatial resolution, noise and contrast, was used to compare the two technologies. Our results show that for a given patient dose, the detection of high and low contrast structures is significantly better for the digital system than for the conventional screen-film system studied. The method of using a test object with a large tissue composition range combined with a camera to compare conventional and digital imaging modalities can be applied to other radiological imaging techniques. In particular it could be used to optimise the process of radiographic reading of soft copy images.

Site-specific coupling between vascular wall thickness and function: an observational MRI study of vessel wall thickening and stiffening in hypertension.

OBJECTIVES: The objective of this study was to evaluate associations between aortic pulse wave velocity (PWV) and aortic and carotid vessel wall thickness (VWT) using cardiovascular magnetic resonance imaging (MRI) in patients with hypertension as compared with healthy adult volunteers. MATERIALS AND METHODS: Local medical ethics approval was obtained and the participants gave informed consent. Fifteen patients with hypertension (5 men and 10 women; mean [SD] age, 49 [14] years) and 15 age- and sex-matched healthy volunteers were prospectively included and compared. All participants underwent MRI examination for measuring aortic and carotid VWT and aortic PWV with well-validated MRI techniques at 1.5- and 3-T MRI systems: PWV was assessed from velocity-encoded MRI and VWT was assessed by using dual-inversion black-blood gradient-echo imaging techniques. Paired t tests were used for testing differences between the volunteers and the patients and Pearson correlation (r) and univariable and multivariable stepwise linear regression analyses were used to test associations between aortic and carotid arterial wall thickness and stiffness. RESULTS: Mean values for aortic PWV and aortic and carotid VWT (indexed for body surface area [BSA]) were all significantly higher in patients with hypertension as compared with the healthy volunteers (ie, aortic PWV, 7.0 ± 1.4 m/s vs 5.7 ± 1.3 m/s; aortic VWT/BSA, 0.12 ± 0.03 mL/m vs 0.10 ± 0.03 mL/m; carotid VWT/BSA, 0.04 ± 0.01 mL/m vs 0.03 ± 0.01 mL/m; all P < 0.01). Aortic PWV was highly correlated with aortic VWT/BSA (r = 0.76 and P = 0.002 in the patients vs r = 0.63 and P = 0.02 in the volunteers), and in the patients, aortic PWV was moderately correlated with carotid VWT/BSA (r = 0.50; P = 0.04). In the volunteers, correlation between aortic PWV and carotid VWT/BSA was not significant (r = 0.40; P = 0.13). In addition, aortic VWT/BSA was significantly correlated with carotid VWT/BSA, in both the patients (r = 0.60; P = 0.005) and volunteers (r = 0.57; P = 0.007). CONCLUSIONS: In the patients with hypertension and the healthy volunteers, the aortic PWV is associated more strongly with aortic wall thickness than with carotid wall thickness, reflecting site-specific coupling between vascular wall thickness and function.

Direct three-dimensional myocardial strain tensor quantification and tracking using zHARP.

Images of myocardial strain can be used to diagnose heart disease, plan and monitor treatment, and to learn about cardiac structure and function. Three-dimensional (3D) strain is typically quantified using many magnetic resonance (MR) images obtained in two or three orthogonal planes. Problems with this approach include long scan times, image misregistration, and through-plane motion. This article presents a novel method for calculating cardiac 3D strain using a stack of two or more images acquired in only one orientation. The zHARP pulse sequence encodes in-plane motion using MR tagging and out-of-plane motion using phase encoding, and has been previously shown to be capable of computing 3D displacement within a single image plane. Here, data from two adjacent image planes are combined to yield a 3D strain tensor at each pixel; stacks of zHARP images can be used to derive stacked arrays of 3D strain tensors without imaging multiple orientations and without numerical interpolation. The performance and accuracy of the method is demonstrated in vitro on a phantom and in vivo in four healthy adult human subjects.

Roles of transient guidepost neurons in corpus callosum formation and guidance

RESUMENeurones transitoires jouant un rôle de cibles intermédiaires dans le guidage des axones du corps calleuxLe guidage axonal est une étape clé permettant aux neurones d'établir des connexions synaptiques et de s'intégrer dans un réseau neural fonctionnel de manière spécifique. Des cellules-cibles intermédiaires appelées « guidepost » aident les axones à parcourir de longues distances dans le cerveau en leur fournissant des informations directionnelles tout au long de leur trajet. Il a été démontré que des sous-populations de cellules gliales au niveau de la ligne médiane guident les axones du corps calleux (CC) d'un hémisphère vers l'autre. Bien qu'il fût observé que le CC en développement contenait aussi des neurones, leur rôle était resté jusqu'alors inconnu.La publication de nos résultats a montré que pendant le développement embryonnaire, le CC contient des glies mais aussi un nombre considérable de neurones glutamatergiques et GABAergiques, nécessaires à la formation du corps calleux (Niquille et al., PLoS Biology, 2009). Dans ce travail, j'ai utilisé des techniques de morphologie et d'imagerie confocale 3D pour définir le cadre neuro-anatomique de notre modèle. De plus, à l'aide de transplantations sur tranches in vitro, de co-explants, d'expression de siRNA dans des cultures de neurones primaires et d'analyse in vivo sur des souris knock-out, nous avons démontré que les neurones du CC guident les axones callosaux en partie grâce à l'action attractive du facteur de guidage Sema3C sur son récepteur Npn- 1.Récemment, nous avons étudié l'origine, les aspects dynamiques de ces processus, ainsi que les mécanismes moléculaires impliqués dans la mise en place de ce faisceau axonal (Niquille et al., soumis). Tout d'abord, nous avons précisé l'origine et l'identité des neurones guidepost GABAergiques du CC par une étude approfondie de traçage génétique in vivo. J'ai identifié, dans le CC, deux populations distinctes de neurones GABAergiques venant des éminences ganglionnaires médiane (MGE) et caudale (CGE). J'ai ensuite étudié plus en détail les interactions dynamiques entre neurones et axones du corps calleux par microscopie confocale en temps réel. Puis nous avons défini le rôle de chaque sous-population neuronale dans le guidage des axones callosaux et de manière intéressante les neurones GABAergic dérivés de la MGE comme ceux de la CGE se sont révélés avoir une action attractive pour les axones callosaux dans des expériences de transplantation. Enfin, nous avons clarifié la base moléculaire de ces mécanismes de guidage par FACS sorting associé à un large criblage génétique de molécules d'intérêt par une technique très sensible de RT-PCR et ensuite ces résultats ont été validés par hybridation in situ.Nous avons également étudié si les neurones guidepost du CC étaient impliqués dans son agénésie (absence de CC), présente dans nombreux syndromes congénitaux chez 1 humain. Le gène homéotique Aristaless (Arx) contrôle la migration des neurones GABAergiques et sa mutation conduit à de nombreuses pathologies humaines, notamment la lissencéphalie liée à IX avec organes génitaux anormaux (XLAG) et agénésie du CC. Fait intéressant, nous avons constaté qu'ARX est exprimé dans toutes les populations GABAergiques guidepost du CC et que les embryons mutant pour Arx présentent une perte drastique de ces neurones accompagnée de défauts de navigation des axones (Niquille et al., en préparation). En outre, nous avons découvert que les souris déficientes pour le facteur de transcription ciliogenic RFX3 souffrent d'une agénésie du CC associé avec des défauts de mise en place de la ligne médiane et une désorganisation secondaire des neurones glutamatergiques guidepost (Benadiba et al., submitted). Ceci suggère fortement l'implication potentielle des deux types de neurones guidepost dans l'agénésie du CC chez l'humain.Ainsi, mon travail de thèse révèle de nouvelles fonctions pour ces neurones transitoires dans le guidage axonal et apporte de nouvelles perspectives sur les rôles respectifs des cellules neuronales et gliales dans ce processus.ABSTRACTRole of transient guidepost neurons in corpus callosum development and guidanceAxonal guidance is a key step that allows neurons to build specific synaptic connections and to specifically integrate in a functional neural network. Intermediate targets or guidepost cells act as critical elements that help to guide axons through long distance in the brain and provide information all along their travel. Subpopulations of midline glial cells have been shown to guide corpus callosum (CC) axons to the contralateral cerebral hemisphere. While neuronal cells are also present in the developing corpus callosum, their role still remains elusive.Our published results unravelled that, during embryonic development, the CC is populated in addition to astroglia by numerous glutamatergic and GABAergic guidepost neurons that are essential for the correct midline crossing of callosal axons (Niquille et al., PLoS Biology, 2009). In this work, I have combined morphological and 3D confocal imaging techniques to define the neuro- anatomical frame of our system. Moreover, with the use of in vitro transplantations in slices, co- explant experiments, siRNA manipulations on primary neuronal culture and in vivo analysis of knock-out mice we have been able to demonstrate that CC neurons direct callosal axon outgrowth, in part through the attractive action of Sema3C on its Npn-1 receptor.Recently, we have studied the origin, the dynamic aspects of these processes as well as the molecular mechanisms involved in the establishment of this axonal tract (Niquille et al., submitted). First, we have clarified the origin and the identity of the CC GABAergic guidepost neurons using extensive in vivo cell fate-mapping experiments. We identified two distinct GABAergic neuronal subpopulations, originating from the medial (MGE) and caudal (CGE) ganglionic eminences. I then studied in more details the dynamic interactions between CC neurons and callosal axons by confocal time-lapse video microscopy and I have also further characterized the role of each guidepost neuronal subpopulation in callosal guidance. Interestingly, MGE- and CGE-derived GABAergic neurons are both attractive for callosal axons in transplantation experiments. Finally, we have dissected the molecular basis of these guidance mechanisms by using FACS sorting combined with an extensive genetic screen for molecules of interest by a sensitive RT-PCR technique, as well as, in situ hybridization.I have also investigated whether CC guidepost neurons are involved in agenesis of the CC which occurs in numerous human congenital syndromes. Aristaless-related homeobox gene (Arx) regulates GABAergic neuron migration and its mutation leads to numerous human pathologies including X-linked lissencephaly with abnormal genitalia (XLAG) and severe CC agenesis. Interestingly, I found that ARX is expressed in all the guidepost GABAergic neuronal populations of the CC and that Arx-/- embryos exhibit a drastic loss of CC GABAergic interneurons accompanied by callosal axon navigation defects (Niquille et al, in preparation). In addition, we discovered that mice deficient for the ciliogenic transcription factor RFX3 suffer from CC agenesis associated with early midline patterning defects and a secondary disorganisation of guidepost glutamatergic neurons (Benadiba et al., submitted). This strongly points out the potential implication of both types of guidepost neurons in human CC agenesis.Taken together, my thesis work reveals novel functions for transient neurons in axonal guidance and brings new perspectives on the respective roles of neuronal and glial cells in these processes.

PPAR disruption: Cellular mechanisms and physiological consequences

Endocrine disruption is defined as the perturbation of the endocrine system, which includes disruption of nuclear hormone receptor signalling. Peroxisome proliferator-activated receptors (PPARs) represent a family of nuclear receptors that has not yet been carefully studied with regards to endocrine disruption, despite the fact that PPARs are known to be important targets for xenobiotics. Here we report a first comprehensive approach aimed at defining the mechanistic basis of PPAR disruption focusing on one chemical, the plasticizer monethylhexyl phthalate (MEHP), but using a variety of methodologies and models. We used mammalian cells and a combination of biochemical and live cell imaging techniques to show that MEHP binds to PPAR gamma and selectively regulates interactions with coregulators. Micro-array experiments further showed that this selectivity is translated at the physiological level during adipocyte differentiation. In that context, MEHP functions as a selective PPAR modulator regulating only a subset of PPAR gamma target genes compared to the action of a full agonist. We also explored the action of MEHP on PPARs in an aquatic species, Xenopus laevis, as many xenobiotics are found in aquatic ecosystems. In adult males, micro-array data indicated that MEHP influences liver physiology, possibly through a cross-talk between PPARs and estrogen receptors (ER). In early Xenopus laevis embryos, we showed that PPAR beta/delta exogenous activation by an agonist or by MEHP affects development. Taken together our results widen the concept of endocrine disruption by pinpointing PPARs as key factors in that process.

The clinical use of quantitative ultrasound (QUS) in the detection and management of osteoporosis

For the detection and management of osteoporosis and osteoporosis-related fractures, quantitative ultrasound (QUS) is emerging as a relatively low-cost and readily accessible alternative to dual-energy X-ray absorptiometry (DXA) measurement of bone mineral density (BMD) in certain circumstances. The following is a brief, but thorough review of the existing literature with respect to the use of QUS in 6 settings: 1) assessing fragility fracture risk; 2) diagnosing osteoporosis; 3) initiating osteoporosis treatment; 4) monitoring osteoporosis treatment; 5) osteoporosis case finding; and 6) quality assurance and control. Many QUS devices exist that are quite different with respect to the parameters they measure and the strength of empirical evidence supporting their use. In general, heel QUS appears to be most tested and most effective. Overall, some, but not all, heel QUS devices are effective assessing fracture risk in some, but not all, populations, the evidence being strongest for Caucasian females over 55 years old. Otherwise, the evidence is fair with respect to certain devices allowing for the accurate diagnosis of likelihood of osteoporosis, and generally fair to poor in terms of QUS use when initiating or monitoring osteoporosis treatment. A reasonable protocol is proposed herein for case-finding purposes, which relies on a combined assessment of clinical risk factors (CR.F) and heel QUS. Finally, several recommendations are made for quality assurance and control.

A connectome-based comparison of diffusion MRI schemes.

Diffusion MRI has evolved towards an important clinical diagnostic and research tool. Though clinical routine is using mainly diffusion weighted and tensor imaging approaches, Q-ball imaging and diffusion spectrum imaging techniques have become more widely available. They are frequently used in research-oriented investigations in particular those aiming at measuring brain network connectivity. In this work, we aim at assessing the dependency of connectivity measurements on various diffusion encoding schemes in combination with appropriate data modeling. We process and compare the structural connection matrices computed from several diffusion encoding schemes, including diffusion tensor imaging, q-ball imaging and high angular resolution schemes, such as diffusion spectrum imaging with a publically available processing pipeline for data reconstruction, tracking and visualization of diffusion MR imaging. The results indicate that the high angular resolution schemes maximize the number of obtained connections when applying identical processing strategies to the different diffusion schemes. Compared to the conventional diffusion tensor imaging, the added connectivity is mainly found for pathways in the 50-100mm range, corresponding to neighboring association fibers and long-range associative, striatal and commissural fiber pathways. The analysis of the major associative fiber tracts of the brain reveals striking differences between the applied diffusion schemes. More complex data modeling techniques (beyond tensor model) are recommended 1) if the tracts of interest run through large fiber crossings such as the centrum semi-ovale, or 2) if non-dominant fiber populations, e.g. the neighboring association fibers are the subject of investigation. An important finding of the study is that since the ground truth sensitivity and specificity is not known, the comparability between results arising from different strategies in data reconstruction and/or tracking becomes implausible to understand.

Surgical interventions with fatal outcome: Utility of multi-phase postmortem CT angiography

Cases of fatal outcome after surgical intervention are autopsied to determine the cause of death and to investigate whether medical error caused or contributed to the death. For medico-legal purposes, it is imperative that autopsy findings are documented clearly. Modern imaging techniques such as multi-detector computed tomography (MDCT) and postmortem CT angiography, which is used for vascular system imaging, are useful tools for determining cause of death. The aim of this study was to determine the utility of postmortem CT angiography for the medico-legal death investigation. This study investigated 10 medico-legal cases with a fatal outcome after surgical intervention using multi-phase postmortem whole body CT angiography. A native CT scan was performed as well as three angiographic phases (arterial, venous, and dynamic) using a Virtangio((R)) perfusion device and the oily contrast agent, Angiofil((R)). The results of conventional autopsy were compared to those from the radiological investigations. We also investigated whether the radiological findings affected the final interpretation of cause-of-death. Causes of death were hemorrhagic shock, intracerebral hemorrhage, septic shock, and a combination of hemorrhage and blood aspiration. The diagnoses were made by conventional autopsy as well as by postmortem CT angiography. Hemorrhage played an important role in eight of ten cases. The radiological exam revealed the exact source of bleeding in seven of the eight cases, whereas conventional autopsy localized the source of bleeding only generally in five of the seven cases. In one case, neither conventional autopsy nor CT angiography identified the source of hemorrhage. We conclude that postmortem CT angiography is extremely useful for investigating deaths following surgical interventions. This technique helps document autopsy findings and allows a second examination if it is needed; specifically, it detects and visualizes the sources of hemorrhages in detail, which is often of particular interest in such cases.

Vessel centerline tracking and boundary sgementation in coronary MRA with minimal manual interaction.

Magnetic resonance angiography (MRA) provides a noninvasive means to detect the presence, location and severity of atherosclerosis throughout the vascular system. In such studies, and especially those in the coronary arteries, the vessel luminal area is typically measured at multiple cross-sectional locations along the course of the artery. The advent of fast volumetric imaging techniques covering proximal to mid segments of coronary arteries necessitates automatic analysis tools requiring minimal manual interactions to robustly measure cross-sectional area along the three-dimensional track of the arteries in under-sampled and non-isotropic datasets. In this work, we present a modular approach based on level set methods to track the vessel centerline, segment the vessel boundaries, and measure transversal area using two user-selected endpoints in each coronary of interest. Arterial area and vessel length are measured using our method and compared to the standard Soap-Bubble reformatting and analysis tool in in-vivo non-contrast enhanced coronary MRA images.

Simultaneous measurement of regional cerebral blood flow by perfusion CT and stable xenon CT: a validation study.

BACKGROUND AND PURPOSE: Knowledge of cerebral blood flow (CBF) alterations in cases of acute stroke could be valuable in the early management of these cases. Among imaging techniques affording evaluation of cerebral perfusion, perfusion CT studies involve sequential acquisition of cerebral CT sections obtained in an axial mode during the IV administration of iodinated contrast material. They are thus very easy to perform in emergency settings. Perfusion CT values of CBF have proved to be accurate in animals, and perfusion CT affords plausible values in humans. The purpose of this study was to validate perfusion CT studies of CBF by comparison with the results provided by stable xenon CT, which have been reported to be accurate, and to evaluate acquisition and processing modalities of CT data, notably the possible deconvolution methods and the selection of the reference artery. METHODS: Twelve stable xenon CT and perfusion CT cerebral examinations were performed within an interval of a few minutes in patients with various cerebrovascular diseases. CBF maps were obtained from perfusion CT data by deconvolution using singular value decomposition and least mean square methods. The CBF were compared with the stable xenon CT results in multiple regions of interest through linear regression analysis and bilateral t tests for matched variables. RESULTS: Linear regression analysis showed good correlation between perfusion CT and stable xenon CT CBF values (singular value decomposition method: R(2) = 0.79, slope = 0.87; least mean square method: R(2) = 0.67, slope = 0.83). Bilateral t tests for matched variables did not identify a significant difference between the two imaging methods (P >.1). Both deconvolution methods were equivalent (P >.1). The choice of the reference artery is a major concern and has a strong influence on the final perfusion CT CBF map. CONCLUSION: Perfusion CT studies of CBF achieved with adequate acquisition parameters and processing lead to accurate and reliable results.

Comparaison objective de systèmes d'imagerie conventionnelle et numérique en mammographie

L'objectif de ce travail est le développement d'une méthode de caractérisation objective de la qualité d'image s'appliquant à des systèmes de mammographie analogique, utilisant un couple écran-film comme détecteur, et numérique, basé sur une technologie semi-conductrice, ceci en vue de la comparaison de leurs performances. La méthode développée tient compte de la gamme dynamique du détecteur, de la détectabilité de structures de haut contraste, simulant des microcalcifications, et de structures de bas contraste, simulant des opacités (nodules tumoraux). La méthode prend également en considération le processus de visualisation de l'image, ainsi que la réponse de l'observateur. Pour réaliser ceci, un objet-test ayant des propriétés proches de celles d'un sein comprimé, composé de différents matériaux équivalents aux tissus, allant du glandulaire à l'adipeux, et comprenant des zones permettant la simulation de structures de haut et bas contraste, ainsi que la mesure de la résolution et celle du bruit, a été développé et testé. L'intégration du processus de visualisation a été réalisée en utilisant une caméra CCD mesurant directement les paramètres de qualité d'image, à partir de l'image de l'objet-test, dans une grandeur physique commune au système numérique et analogique, à savoir la luminance arrivant sur l'oeil de l'observateur. L'utilisation d'une grandeur synthétique intégrant dans un même temps, le contraste, le bruit et la résolution rend possible une comparaison objective entre les deux systèmes de mammographie. Un modèle mathématique, simulant la réponse d'un observateur et intégrant les paramètres de base de qualité d'image, a été utilisé pour calculer la détectabilité de structures de haut et bas contraste en fonction du type de tissu sur lequel celles-ci se trouvent. Les résultats obtenus montrent qu'à dose égale la détectabilité des structures est significativement plus élevée avec le système de mammographie numérique qu'avec le système analogique. Ceci est principalement lié au fait que le bruit du système numérique est plus faible que celui du système analogique. Les résultats montrent également que la méthodologie, visant à comparer des systèmes d'imagerie numérique et analogique en utilisant un objet-test à large gamme dynamique ainsi qu'une caméra, peut être appliquée à d'autres modalités radiologiques, ainsi qu'à une démarche d'optimisation des conditions de lecture des images.<br/><br/>The goal of this work was to develop a method to objectively compare the performance of a digital and a screen-film mammography system in terms of image quality and patient dose. We propose a method that takes into account the dynamic range of the image detector and the detection of high contrast (for microcalcifications) and low contrast (for masses or tumoral nodules) structures. The method also addresses the problems of image visualization and the observer response. A test object, designed to represent a compressed breast, was constructed from various tissue equivalent materials ranging from purely adipose to purely glandular composition. Different areas within the test object permitted the evaluation of low and high contrast detection, spatial resolution, and image noise. All the images (digital and conventional) were captured using a CCD camera to include the visualization process in the image quality assessment. In this way the luminance reaching the viewer?s eyes can be controlled for both kinds of images. A global quantity describing image contrast, spatial resolution and noise, and expressed in terms of luminance at the camera, can then be used to compare the two technologies objectively. The quantity used was a mathematical model observer that calculates the detectability of high and low contrast structures as a function of the background tissue. Our results show that for a given patient dose, the detection of high and low contrast structures is significantly better for the digital system than for the conventional screen-film system studied. This is mainly because the image noise is lower for the digital system than for the screen-film detector. The method of using a test object with a large dynamic range combined with a camera to compare conventional and digital imaging modalities can be applied to other radiological imaging techniques. In particular it could be used to optimize the process of radiographic film reading.

Towards desired crystalline product properties: In-situ monitoring of batch crystallization

The objective of industrial crystallization is to obtain a crystalline product which has the desired crystal size distribution, mean crystal size, crystal shape, purity, polymorphic and pseudopolymorphic form. Effective control of the product quality requires an understanding of the thermodynamics of the crystallizing system and the effects of operation parameters on the crystalline product properties. Therefore, obtaining reliable in-line information about crystal properties and supersaturation, which is the driving force of crystallization, would be very advantageous. Advanced techniques, such asRaman spectroscopy, attenuated total reflection Fourier transform infrared (ATR FTIR) spectroscopy, and in-line imaging techniques, offer great potential for obtaining reliable information during crystallization, and thus giving a better understanding of the fundamental mechanisms (nucleation and crystal growth) involved. In the present work, the relative stability of anhydrate and dihydrate carbamazepine in mixed solvents containing water and ethanol were investigated. The kinetics of the solvent mediated phase transformation of the anhydrate to hydrate in the mixed solvents was studied using an in-line Raman immersion probe. The effects of the operation parameters in terms of solvent composition, temperature and the use of certain additives on the phase transformation kineticswere explored. Comparison of the off-line measured solute concentration and the solid-phase composition measured by in-line Raman spectroscopy allowedthe identification of the fundamental processes during the phase transformation. The effects of thermodynamic and kinetic factors on the anhydrate/hydrate phase of carbamazepine crystals during cooling crystallization were also investigated. The effect of certain additives on the batch cooling crystallization of potassium dihydrogen phosphate (KDP) wasinvestigated. The crystal growth rate of a certain crystal face was determined from images taken with an in-line video microscope. An in-line image processing method was developed to characterize the size and shape of thecrystals. An ATR FTIR and a laser reflection particle size analyzer were used to study the effects of cooling modes and seeding parameters onthe final crystal size distribution of an organic compound C15. Based on the obtained results, an operation condition was proposed which gives improved product property in terms of increased mean crystal size and narrowersize distribution.