Prospective and retrospective motion correction in diffusion magnetic resonance imaging of the human brain.

Diffusion-weighting in magnetic resonance imaging (MRI) increases the sensitivity to molecular Brownian motion, providing insight in the micro-environment of the underlying tissue types and structures. At the same time, the diffusion weighting renders the scans sensitive to other motion, including bulk patient motion. Typically, several image volumes are needed to extract diffusion information, inducing also inter-volume motion susceptibility. Bulk motion is more likely during long acquisitions, as they appear in diffusion tensor, diffusion spectrum and q-ball imaging. Image registration methods are successfully used to correct for bulk motion in other MRI time series, but their performance in diffusion-weighted MRI is limited since diffusion weighting introduces strong signal and contrast changes between serial image volumes. In this work, we combine the capability of free induction decay (FID) navigators, providing information on object motion, with image registration methodology to prospectively--or optionally retrospectively--correct for motion in diffusion imaging of the human brain. Eight healthy subjects were instructed to perform small-scale voluntary head motion during clinical diffusion tensor imaging acquisitions. The implemented motion detection based on FID navigator signals is processed in real-time and provided an excellent detection performance of voluntary motion patterns even at a sub-millimetre scale (sensitivity≥92%, specificity>98%). Motion detection triggered an additional image volume acquisition with b=0 s/mm2 which was subsequently co-registered to a reference volume. In the prospective correction scenario, the calculated motion-parameters were applied to perform a real-time update of the gradient coordinate system to correct for the head movement. Quantitative analysis revealed that the motion correction implementation is capable to correct head motion in diffusion-weighted MRI to a level comparable to scans without voluntary head motion. The results indicate the potential of this method to improve image quality in diffusion-weighted MRI, a concept that can also be applied when highest diffusion weightings are performed.

Relationship between imaging biomarkers, age, progression and symptom severity in Alzheimer's disease.

The early diagnostic value of glucose hypometabolism and atrophy as potential neuroimaging biomarkers of mild cognitive impairment (MCI) and Alzheimer's disease (AD) have been extensively explored using [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) and structural magnetic resonance imaging (MRI). The vast majority of previous imaging studies neglected the effects of single factors, such as age, symptom severity or time to conversion in MCI thus limiting generalisability of results across studies. Here, we investigated the impact of these factors on metabolic and structural differences. FDG-PET and MRI data from AD patients (n = 80), MCI converters (n = 65) and MCI non-converters (n = 64) were compared to data of healthy subjects (n = 79). All patient groups were split into subgroups by age, time to conversion (for MCI), or symptom severity and compared to the control group. AD patients showed a strongly age-dependent pattern, with younger patients showing significantly more extensive reductions in gray matter volume and glucose utilisation. In the MCI converter group, the amount of glucose utilisation reduction was linked to the time to conversion but not to atrophy. Our findings indicate that FDG-PET might be more closely linked to future cognitive decline whilst MRI being more closely related to the current cognitive state reflects potentially irreversible damage.

MRI of coronary vessel walls using radial k-space sampling and steady-state free precession imaging.

OBJECTIVE: The objective of our study was to investigate the impact of radial k-space sampling and steady-state free precession (SSFP) imaging on image quality in MRI of coronary vessel walls. SUBJECTS AND METHODS: Eleven subjects were examined on a 1.5-T MR system using three high-resolution navigator-gated and cardiac-triggered 3D black blood sequences (cartesian gradient-echo [GRE], radial GRE, and radial SSFP) with identical spatial resolution (0.9 x 0.9 x 2.4 mm3). The signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), vessel wall sharpness, and motion artifacts were analyzed. RESULTS: The mean SNR and CNR of the coronary vessel wall were improved using radial imaging and were best using radial k-space sampling combined with SSFP imaging. Vessel border definition was similar for all three sequences. Radial k-space sampling was found to be less sensitive to motion. Consistently good image quality was seen with the radial GRE sequence. CONCLUSION: Radial k-space sampling in MRI of coronary vessel walls resulted in fewer motion artifacts and improved SNR and CNR. The use of SSFP imaging, however, did not result in improved coronary vessel wall visualization.

The presence of conifer resin decreases the use of the immune system in wood ants

1. Wood ants (Formica paralugubris) incorporate large amounts of solidified conifer resin into their nest, which reduces the density of many bacteria and fungi and protects the ants against some detrimental micro-organisms. By inducing an environment unfavourable to pathogens, the presence of resin may allow workers to reduce the use of their immune system. 2. The present study tested the hypothesis that the presence of resin decreases the immune activity of wood ants. Specifically, three components of the humoral immune defences of workers kept in resin-rich and resin-free experimental nests (antibacterial, lytic, and prophenoloxidase activities) were compared. 3. The presence of resin was associated with reduced bacterial and fungal densities in nest material and with a small decrease in worker antibacterial and lytic activities. The prophenoloxidase activity was very low in all workers and was not affected by the presence of resin. 4. These results suggest that collective medication with resin reduces pathogen pressure, which in turn decreases the use of the inducible part of the immune system. More generally, the use of plant secondary compounds might be an efficient and economical way to fight pathogens.

Continuous electroencephalographic monitoring in critically ill patients with central nervous system infections.

OBJECTIVES: To determine the prevalence, predictors, and clinical significance of electrographic seizures (ESz) and other continuous electroencephalographic monitoring findings in critically ill patients with central nervous system infections. DESIGN: Retrospective cohort study. SETTING: Eighteen-bed neurocritical care unit. PATIENTS: We identified 42 consecutive patients with primary central nervous system infection (viral, 27 patients [64%]; bacterial, 8 patients [18%]; and fungal or parasitic, 7 patients [17%]) who underwent continuous electroencephalographic monitoring between January 1, 1996, and February 28, 2007. MAIN OUTCOME MEASURES: Presence of ESz or periodic epileptiform discharges (PEDs). RESULTS: Electrographic seizures were recorded in 14 patients (33%), and PEDs were recorded in 17 patients (40%). Twenty patients (48%) had either PEDs or ESz. Of the 14 patients with ESz, only 5 (36%) had a clinical correlate. Periodic epileptiform discharges (odds ratio=13.4; P=.001) and viral cause (odds ratio=13.0; P=.02) were independently associated with ESz. Both ESz (odds ratio=5.9; P=.02) and PEDs (odds ratio=6.1; P=.01) were independently associated with poor outcome at discharge (severe disability, vegetative state, or death). CONCLUSIONS: In patients with central nervous system infections undergoing continuous electroencephalographic monitoring, ESz and/or PEDs were frequent, occurring in 48% of our cohort. More than half of the ESz had no clinical correlate. Both ESz and PEDs were independently associated with poor outcome. Additional studies are needed to determine whether prevention or treatment of these electrographic findings improves outcome.

Tumeurs de l'appareil locomoteur: de la simple "bosse" a la prise en charge multidisciplinaire [Tumors of the musculoskeletal system: from the "lumps" to multidisciplinary care].

Management of musculoskeletal tumours usually begins with the appearance of a lump or bump, or the onset of unspecific symptoms. A poor initial work-up, a faulty biopsy or an inadequate resection may have a severe impact on the prognosis, including re-interventions, amputation, local recurrence or systemic spread of the disease. The patient with a suspicious lesion should be referred to a "sarcoma centers" where a planned and well-performed diagnostic work-up will allow a precise diagnosis in terms of histology and staging. After a multidisciplinary discussion of the case, an accurate treatment plan is established. Such an approach allows an adequate patient management, often with a positive impact on the survival and functional outcome.

Sustained 24-hour blockade of the renin-angiotensin system: a high dose of a long-acting blocker is as effective as a lower dose combined with an angiotensin-converting enzyme inhibitor

Résumé en français Jusqu'alors, il n'avait jamais été formellement démontré qu'une forte dose d'un antagoniste de l'angiotensine II à longue durée d'action pouvait être aussi efficace sur le blocage du système rénine-angiotensine que l'association d'un inhibiteur de l'enzyme de conversion avec le même antagoniste de l'angiotensine II à des doses plus faibles. Dans cette étude randomisée en double aveugle, nous avons étudié le blocage du système rénine-angiotensine obtenu avec trois doses d'olmesartan medoxomil (20, 40 et 80 mg) chez 30 volontaires sains que nous avons comparé au blocage obtenu par du lisinopril (20 mg), seul ou associé à de l'olmesartan medoxomil (20 et 40 mg). L'étude s'est déroulée en deux phases selon un design par crossover. A deux reprises, chaque volontaire à reçu durant une semaine l'un des six traitements possibles. Un intervalle d'une semaine a été respecté entre les deux phases (période de washout). L'objectif principal était d'étudier, 24 heures après la dernière dose, le blocage de l'élévation de la pression systolique en réponse à l'administration d'angiotensine I. Ce blocage était de 58% ± 19% (moyenne ± déviation standard) avec 20 mg de lisinopril, de 58% ± 11% avec 20 mg d'olmesartan medoxomil, de 62% ± 16% avec 40 mg d'olmesartan medoxomil, et de 76% ± 12% avec la plus forte dose d'olmesartan medoxomil (80 mg) (P=.016 versus 20 mg de lisinopril et P=.0015 versus 20 mg d'olmesartan medoxomil). Le blocage était de 80% ± 22% avec 20 mg de lisinopril associé à 20 mg d'olmesartan medoxomil et de 83% ± 9% avec 20 mg de lisinopril associé à 40 mg d'olmesartan medoxomil (P= .3 versus 80 mg d'olmesartan medoxomil). Ces résultats montrent, que chez les volontaires sains, une dose suffisamment élevée d'olmesartan medoxomil peut induire un blocage à 24 heures quasi complet de l'élévation de la pression artérielle en réponse à l'administration d'angiotensine I. De même, en terme de blocage de l'effet vasculaire de l'angiotensine I, une dose suffisamment élevée d'un antagoniste de l'angiotensine II de longue durée d'action est tout aussi efficace que ce même antagoniste à des doses plus faibles associé avec à un inhibiteur de l'enzyme de conversion.

Electronic Construction Collaboration System – Final Phase, SPR RB02-008, 2014

This phase of the research project involved two major efforts: (1) Complete the implementation of AEC-Sync (formerly known as Attolist) on the Iowa Falls Arch Bridge project and (2) develop a web-based project management system (WPMS) for projects under $10 million. For the first major effort, AEC-Sync was provided for the Iowa Department of Transportation (DOT) in a software as a service agreement, allowing the Iowa DOT to rapidly implement the solution with modest effort. During the 2010 fiscal year, the research team was able to help with the implementation process for the solution. The research team also collected feedback from the Broadway Viaduct project team members before the start of the project and implementation of the solution. For the 2011 fiscal year, the research team collected the post-project surveys from the Broadway Viaduct project members and compared them to the pre-project survey results. The result of the AEC-Sync implementation in the Broadway Viaduct project was a positive one. The project members were satisfied with the performance of AEC-Sync and how it facilitated document management and transparency. In addition, the research team distributed, collected, and analyzed the pre-project surveys for the Iowa Falls Arch Bridge project. During the 2012 fiscal year, the research team analyzed the post-project surveys for the Iowa Falls Arch Bridge project AEC-Sync implementation and found a positive outcome when compared to the pre-project surveys. The second major effort for this project involved the identification and implementation of a WPMS solution for smaller bridge and highway projects. During the 2011 fiscal year, Microsoft SharePoint was selected to be implemented on these smaller highway projects. In this year, workflows for the shop/working drawings for the smaller highway projects specified in Section 1105 of the Iowa DOT Specifications were developed. These workflows will serve as the guide for the development of the SharePoint pages. In order to implement the Microsoft SharePoint pages, the effort of an integrated team proved to be vital because it brought together the expertise required from researchers, programmers, and webpage developers to develop the SharePoint pages.

Phenotip - a web-based instrument to help diagnosing fetal syndromes antenatally.

Prenatal ultrasound can often reliably distinguish fetal anatomic anomalies, particularly in the hands of an experienced ultrasonographer. Given the large number of existing syndromes and the significant overlap in prenatal findings, antenatal differentiation for syndrome diagnosis is difficult. We constructed a hierarchic tree of 1140 sonographic markers and submarkers, organized per organ system. Subsequently, a database of prenatally diagnosable syndromes was built. An internet-based search engine was then designed to search the syndrome database based on a single or multiple sonographic markers. Future developments will include a database with magnetic resonance imaging findings as well as further refinements in the search engine to allow prioritization based on incidence of syndromes and markers.

Roles of astrocytic sodium dynamics in the neurometabolic coupling : a study by cellular imaging

RESUME LARGE PUBLIC Le système nerveux central est principalement composé de deux types de cellules :les neurones et les cellules gliales. Ces dernières, bien que l'emportant en nombre sur les neurones, ont longtemps été considérées comme des cellules sans intérêts par les neuroscientifiques. Hors, les connaissances modernes à leurs sujets indiquent qu'elles participent à la plupart des tâches physiologiques du cerveau. Plus particulièrement, elles prennent part aux processus énergétiques cérébraux. Ceux-ci, en plus d'être vitaux, sont particulièrement intrigants puisque le cerveau représente seulement 2 % de la masse corporelle mais consomme environ 25 % du glucose (substrat énergétique) corporel. Les astrocytes, un type de cellules gliales, jouent un rôle primordial dans cette formidable utilisation de glucose par le cerveau. En effet, l'activité neuronale (transmission de l'influx nerveux) est accompagnée d'une augmentation de la capture de glucose, issu de la circulation sanguine, par les astrocytes. Ce phénomène est appelé le «couplage neurométabolique » entre neurones et astrocytes. L'ion sodium fait partie des mécanismes cellulaires entrant en fonction lors de ces processus. Ainsi, dans le cadre de cette thèse, les aspects dynamiques de la régulation du sodium astrocytaire et leurs implications dans le couplage neurométabolique ont été étudiés par des techniques d'imagerie cellulaires. Ces études ont démontré que les mitochondries, machineries cellulaires convertissant l'énergie contenue dans le glucose, participent à la régulation du sodium astrocytaire. De plus, ce travail de thèse a permis de découvrir que les astrocytes sont capables de se transmettre, sous forme de vagues de sodium se propageant de cellules en cellules, un message donnant l'ordre d'accroître leur consommation d'énergie. Cette voie de signalisation leur permettrait de fournir de l'énergie aux neurones suite à leur activation. RESUME Le glutamate libéré dans la fente synaptique pendant l'activité neuronale, est éliminé par les astrocytes environnants. Le glutamate est co-transporté avec des ions sodiques, induisant une augmentation intracellulaire de sodium (Na+i) dans les astrocytes. Cette élévation de Na+i déclenche une cascade de mécanismes moléculaires qui aboutissent à la production de substrats énergétiques pouvant être utilisés par les neurones. Durant cette thèse, la mesure simultanée du sodium mitochondrial (Na+mit) et cytosolique par des techniques d'imagerie utilisant des sondes fluorescentes spécifiques, a indiqué que les variations de Na+i induites par le transport du glutamate sont transmises aux mitochondries. De plus, les voies d'entrée et de sortie du sodium mitochondrial ont été identifiées. L'échangeur de Na+ et de Ca2+ mitochondrial semble jouer un rôle primordial dans l'influx de Na+mit, alors que l'efflux de Na+mit est pris en charge par l'échangeur de Na+ et de H+ mitochondrial. L'étude du Na+mit a nécessité l'utilisation d'un système de photoactivation. Les sources de lumière ultraviolette (UV) classiques utilisées à cet effet (lasers, lampes à flash) ayant plusieurs désavantages, une alternative efficace et peu coûteuse a été développée. Il s'agit d'un système compact utilisant une diode électroluminescente (LED) à haute puissance et de longueur d'onde de 365nm. En plus de leurs rôles dans le couplage neurométabolique, les astrocytes participent à la signalisation multicellulaire en transmettant des vagues intercellulaires de calcium. Ce travail de thèse démontre également que des vagues intercellulaires de sodium peuvent être évoquées en parallèle à ces vagues calciques. Le glutamate, suite à sa libération par un mécanisme dépendent du calcium, est réabsorbé par les transporteurs au glutamate. Ce mécanisme a pour conséquence la génération de vagues sodiques se propageant de cellules en cellules. De plus, ces vagues sodiques sont corrélées spatialement avec une consommation accrue de glucose par les astrocytes. En conclusion, ce travail de thèse a permis de montrer que le signal sodique astrocytaire, déclenché en réponse au glutamate, se propage à la fois de façon intracellulaire aux mitochondries et de façon intercellulaire. Ces résultats suggèrent que les astrocytes fonctionnent comme un réseau de cellules nécessaire au couplage énergétique concerté entre neurones et astrocytes et que le sodium est un élément clé dans les mécanismes de signalisations cellulaires sous-jacents. SUMMARY Glutamate, released in the synaptic cleft during neuronal activity, is removed by surrounding astrocytes. Glutamate is taken-up with Na+ ions by specific transporters, inducing an intracellular Na+ (Na+i) elevation in astrocytes which triggers a cascade of molecular mechanisms that provides metabolic substrates to neurons. Thus, astrocytic Na+i homeostasis represents a key component of the so-called neurometabolic coupling. In this context, the first part of this thesis work was aimed at investigating whether cytosolic Na+ changes are transmitted to mitochondria, which could therefore influence their function and contribute to the overall intracellular Na+ regulation. Simultaneous monitoring of both mitochondrial Na+ (Na+mit) and cytosolic Na+ changes with fluorescent dyes revealed that glutamate-evoked cytosolic Na+ elevations are indeed transmitted to mitochondria. The mitochondrial Na+/Ca2+ exchangers have a prominent role in the regulation of Na+mit influx pathway, and Na+mit extrusion appears to be mediated by Na+/H+ exchangers. To demonstrate the implication of Na+/Ca2+ exchangers, this study has required the technical development of an UV-flash photolysis system. Because light sources for flash photolysis have to be powerful and in the near UV range, the use of UV lasers or flash lamps is usually required. As an alternative to these UV sources that have several drawbaks, we developped a compact, efficient and lowcost flash photolysis system which employs a high power 365nm light emitting diode. In addition to their role in neurometabolic coupling, astrocytes participate in multicellular signaling by transmitting intercellular Ca2+ waves. The third part of this thesis show that intercellular Na+ waves can be evoked in parallel to Ca2+ waves. Glutamate released by a Ca2+ wave-dependent mechanism is taken up by glutamate transporters, resulting in a regenerative propagation of cytosolic Na+ increases. Na+ waves in turn lead to a spatially correlated increase in glucose uptake. In conclusion, the present thesis demonstrates that glutamate-induced Na+ changes occurring in the cytosol of astrocytes propagate to both the mitochondrial matrix and the astrocytic network. These results furthermore support the view that astrocytic Na+ is a signal coupled to the brain energy metabolism.

Can 3T multiparametric magnetic resonance imaging accurately detect prostate cancer extracapsular extension?

BACKGROUND: Accurate staging is essential to determine the correct management of patients diagnosed with prostate cancer. We assess the accuracy of 3T multiparametric magnetic resonance imaging (MRI) with endorectal coil (3TemMRI) in detecting prostate cancer local extension. METHODS: We retrospectively reviewed charts from January 2008 to July 2012 from all patients undergoing radical prostatectomy. Patients were only included if 3TemMRI and radical prostatectomy were performed at our institution. Based on the presence of extracapsular extension (ECE) at 3TemMRI, prostate cancer was dichotomized into locally advanced or organ-confined disease. The accuracy of 3TemMRI local staging was then evaluated using definitive pathology as a reference. RESULTS: Overall, 177 radical prostatectomies were performed within the timeframe. After applying exclusion criteria, 60 patients were included in the final analysis. The mean patient age was 67 ± 7 (standard deviation) years. Mean prostate-specific antigen value was 12.7 ± 12.7 ng/L. Based on preoperative characteristics, we considered 38 of the 60 patients (63%) patients high risk. 3TemMRI identified an organ-confined tumour in 46 patients and locally advanced disease in 14 patients. When correlated to final pathology, 3TemMRI specificity, sensitivity, negative and positive predictive values, and accuracy in detecting locally advanced prostate cancer were 90%, 35%, 57%, 79% and 62%, respectively. INTERPRETATION: This study shows that the use of preoperative 3TemMRI can be used to identify organ-confined prostate cancer when locally advanced disease is suspected.

La PMU au carrefour des nouveaux chemins du système de santé [Redesigning Swiss ambulatory health care system].

Primary care medicine is first in line to meet the necessary changes in our health care system. Innovations in this field pursue three types of objectives: accessibility, quality and continuity of care. The Department of ambulatory care and community medicine of the University of Lausanne (Policlinique médicale universitaire) is committed to this path, emphasizing interprofessional collaboration. The doctor, nurse and medical assistant coordinate their activities to contribute efficiently to meet the needs of patients today and tomorrow. This paper also addresses how our department, as a public and academic institution, might play a major role as a health care network actor. A master degree dissertation in health management has started to identify the critical success factors and the strategic core competencies needed to achieve this development.