En biologie développementale, l'étude d'organismes modèles vise à comprendreles mécanismes génétiques responsables de la morphogenèse chez le vivant. Lamicroscopie confocale à fluorescence permet aujourd'hui d'observer in vivo àl'échelle de la cellule et avec une haute fréquence temporelle le développementd'organismes. Les séquences d'images 3D+t ainsi obtenues nécessitent d'avoirdes outils de traitement d'images adaptés.Dans cette thèse, nous construisons des outils dédiés à l'étude dudéveloppement de deux organismes, l'embryon de l'ascidie Phallusiamammillata et le bouton floral d'Arabidopsis thaliana.Nous développons d'abord une méthode de comparaison de segmentationsadaptée aux images de tissus épithéliaux d'organismes en développement.Nous nous appuyons sur cet outil pour valider notre seconde contribution quiporte sur la mise en place d'un outil de détection et de reconstruction demembranes cellulaires conçu afin de procéder à la segmentation de cellulesdans les images d'ascidies et d'arabidopsis.Nous utilisons ensuite l'outil de segmentation de membranes précédemmentintroduit pour construire une stratégie de recalage spatial inter-individusappliquée aux embryons d'ascidies. Enfin, nous élaborons une stratégie derecalage spatio-temporel inter-individus appliquée à des séquences d'images 3Dde méristèmes floraux / In developmental biology, the study of model organisms aims for theunderstanding of genetic mechanisms responsible of morphogenesis. Today,fluorescent confocal microscopy is a means for in vivo imaging of developingorganisms at cell level with a high spatio-temporal resolution. To handle such3D+t image sequences, adapted computer-assisted methods are highlydesirable.In this thesis, we build dedicated tools for the study of two developingorganisms, the ascidian Phallusia mammillata's embryo and the Arabidopsisthaliana's floral meristem.We first develop a method for segmentation comparison adapted to developingorganism epithelial tissue images. This tool is then used to validate our secondcontribution that is about the development of a cell membranes detection andreconstruction tool for cell shape segmentation process applied to ascidian andarabidopsis images.We then use the previously introduced membrane detection tool to build aninter-individual spatial registration strategy applied to ascidian embryo images.Finally, we develop an inter-individual spatio-temporal registration strategyapplied to 3D image sequences of arabidopsis floral meristems

Geometric morphometry serves biologists and anthropologists to rigorously and quantitatively describe shapes. These representations can be treated as a statistical sample, allowing the researchers to study its variability within groups and correlate it to other features. Geometric morphometry uses landmarks as the proxy for shape, with consistent semantics in each specimen. General triangle meshes do not have this property, and as such, semantically consistent remeshes must be created artificially. This thesis deals with the design of an algorithm that consistently resamples a set of surface models for the purpose of statistical analysis. Coherent point drift was employed to perform nonrigid registration, whose result is then used to generate a semantically consistent remeshes. This approach was successfully applied in a number of studies. As CPD is compute-intensive, we propose methods of accelerating both its initialization and processing phases. Also, an extension was introduced, that can map the deviation of the surfaces from perfect bilateral symmetry and analyze it in a sample, which is significant, among others, for quantification of pathologies. Manual trimming of the surfaces and merging datasets results in outlier regions in the individual surfaces and potentially large differences in their vertex...

Magister Pharmaceuticae - MPharm / Medicines registration decision-making and regulatory best practice involve transparent and consistent rule making and processes with publicly available published assessment decisions and reports (Kaine, 2020). Publication of information relating to evaluation of medicines in the form of Public Assessment Reports (PARs) is one way of ensuring transparency in medicines registration decision making. It is however not clear whether National Medicines Regulatory Authorities (NMRAs) in the Southern African Development Community (SADC) region are in a position to generate or even publish such PARs / summary basis for registration of medicines. Objectives: The study investigated transparency in medicines registration decision-making processes for NMRAs within the SADC region. Specifically, the availability or non-availability of PARs / Summary basis for registration of medicinal products. To establish if all SADC NMRAs have legislative frameworks for regulating medicines and to investigate the sources of funding for SADC NMRAs. Methods: A cross-sectional exploratory descriptive study design with qualitative techniques by questionnaire as a data collection tool was used. Questionnaires were sent via email to senior members / key informants of 11 regulatory authorities belonging to SADC. Trend analysis was conducted based on the emerging themes from questionnaire response. Results The study revealed that currently five (5) NMRAs are operating as semi-autonomous agencies namely: BOMRA, MCAZ, PMRA, SAHPRA and TMDA .While NMRC, DNME of Angola, ACOREP of DRC and DNF of Mozambique are functioning within their respective Ministries of Health Departments. Furthermore, all NMRAs have a legislation framework governing the regulation of medicines in their respective jurisdictions. However, DNME of Angola’s legal framework is not yet officially formalised and as such, they follow a Presidential decree enacted in 2010. Four (4) of nine (9) NMRAs (44 %) reported to have more than 20 internal assessors / evaluators. This indicates a significant milestone for SADC NMRAs in terms of capacity building within the region. The study findings indicated that the SADC NMRAs are receiving funding from multiple sources ranging from a minimum of one to maximum of four funding sources. There were only two NMRAs, MCAZ and PMRA, that were not receiving funding from their governments. The study results further indicates that only TMDA is able to generate and publish PARs amongst SADC NMRAs. Conclusions: The findings in this study suggest that the majority of NMRAs within SADC are not yet matured as compared to countries in the developed world such as the US, Europe, Canada and Australia. It can also be concluded that for SADC NMRAs to be efficient and responsive, they will require massive financial resources. For example, the budget for a matured NMRA such as the US Food and Drug Administration (US FDA) for the 2019 financial year was estimated at US$ 5.7 billion. Literature further indicates that publication of the summary basis of approval or PARs is a norm for mature NMRAs and acts as a tool for regulatory authorities to build and establish confidence in their review processes and provides assurance regarding safety of medicines. The study results indicate that TMDA is publishing PARs or summary of grounds on which approvals are granted. This demonstrates a significant level of transparency in the TMDA medicines registration processes and therefore other SADC NMRAs can benchmark with TMDA to implement this key parameter.

In order to analyse body composition of MRI (Magnetic Resonance Imaging) volumes, atlas-based segmentation is often used to retrieve information from specific organs or anatomical regions. The method behind this technique is to use an already segmented image volume, an atlas, to segment a target image volume by registering the volumes to each other. During this registration a deformation field will be calculated, which is applied to a segmented part of the atlas, resulting in the same anatomical segmentation in the target. The drawback with this method is that the quality of the segmentation is highly dependent on the similarity between the target and the atlas, which means that many atlases are needed to obtain good segmentation results in large sets of MRI volumes. One potential solution to overcome this problem is to create the deformation field between a target and an atlas as a sequence of small deformations between more similar bodies.  In this master thesis a new method for atlas-based segmentation has been developed, with the anticipation of obtaining good segmentation results regardless of the level of similarity between the target and the atlas. In order to do so, 4000 MRI volumes were used to create a manifold of human bodies, which represented a large variety of different body types. These MRI volumes were compared to each other and the calculated similarities were saved in matrices called similarity models. Three different similarity measures were used to create the models which resulted in three different versions of the model. In order to test the hypothesis of achieving good segmentation results when the deformation field was constructed as a sequence of small deformations, the similarity models were used to find the shortest path (the path with the least dissimilarity) between a target and an atlas in the manifold.  In order to evaluate the constructed similarity models, three MRI volumes were chosen as atlases and 100 MRI volumes were randomly picked to be used as targets. The shortest paths between these volumes were used to create the deformation fields as a sequence of small deformations. The created fields were then used to segment the anatomical regions ASAT (abdominal subcutaneous adipose tissue), LPT (left posterior thigh) and VAT (visceral adipose tissue). The segmentation performance was measured with Dice Index, where segmentations constructed at AMRA Medical AB were used as ground truth. In order to put the results in relation to another segmentation method, direct deformation fields between the targets and the atlases were also created and the segmentation results were compared to the ground truth with the Dice Index. Two different types of transformation methods, one non-parametric and one affine transformation, were used to create the deformation fields in this master thesis. The evaluation showed that good segmentation results can be achieved for the segmentation of VAT for one of the constructed similarity models. These results were obtained when a non-parametric registration method was used to create the deformation fields. In order to achieve similar results for an affine registration and to improve the segmentation of other anatomical regions, further investigations are needed.

Airway hyperresponsiveness (AHR) is a hallmark of asthma where constriction of airway smooth muscle (ASM) causes excessive airway narrowing. Asthmatics, unlike healthy subjects, cannot prevent or reverse this narrowing by stretching their airways with a deep inspiration (DI). Since stretching of isolated ASM causes dramatic reductions in force generation and asthmatics tend to have stiffer airways, researchers hypothesize that reduced ASM stretching during breathing and DIs results in hyperreactive airways. However, counterintuitively, excised measurement on intact airways show narrowing is minimally reversed by pressure oscillations simulating breathing and DIs. We hypothesized that AHR does not result from reduced capacity to stretch the airways; furthermore, each constituent of the airway wall experiences different strain magnitude during breathing and DIs. To test this, we used an intact airway system which controls transmural pressure (Ptm) to simulate breathing while measuring luminal diameter in response to ASM agonists. An ultrasound system and automated segmentation algorithm were implemented to quantify and compare the ability of Ptm fluctuations to reverse and prevent narrowing in larger (diameter=5.72±0.52mm) relative to smaller airways (diameter=2.92±0.29mm). We found the ability of Ptm oscillations to reverse airway narrowing was proportional to strain imposed on the airway wall. Further, tidal-like breathing Ptm oscillations (5-15cmH2O) after constriction imposed 196% more strain in smaller compared to larger airways (14.6% vs. 5.58%), resulting in 76% greater reversal of narrowing (41.2% vs. 23.4%). However, Ptm oscillations applied before and during constriction resulted in the same steady-state diameter as when Ptm oscillations were applied only after constriction. To better understand these results, we optimized an ultrasound elastography technique utilizing finite element-based image registration to estimate spatial distributions of displacements, strains, and material properties throughout an airway wall during breathing and bronchoconstriction. This required we formulate and solve an inverse elasticity problem to reconstruct the distribution of nonlinear material properties. Strains and material properties were radially and longitudinally heterogeneous, and patterns and magnitudes changed significantly after induced narrowing. Taken together, these data show AHR likely does not emerge due to reduced straining of airways prior to challenge, but remodeling that stiffens airway walls might serve to sustain constriction during an asthmatic-like attack.

Dénommée multiparamétrique par adjonction de séquences fonctionnelle aux conventionnelles, L’IRM de prostate a montré ses performances pour la détection du cancer de prostate par un score radiologique visuel, subjectif. D’autres applications sont en cours d’investigations comme la stratification, le planning thérapeutique ou encore le suivi oncologique.La première partie s’attache à décrire, élaborer et appliquer une méthodologie de recalage non rigide en 3D entre l’histologie du spécimen de prostatectomie totale et les différentes séquences de l’IRMmp. Après avoir capturé une déformation et un changement de volume de la prostate entre les états in vivo et ex vivo par IRM, la méthode de recalage multimodalité appliquée à une population de prostatectomie totale précédée d’une IRM démontre une sous-estimation du volume de cancer par l’IRM, sujette à une stratification. Les implications se trouvent dans la détection, la stratification et le planning thérapeutique. La deuxième partie propose une analyse de texture des différentes séquences et cartographies quantitatives en diffusion et perfusion pour la détection et la stratification du cancer. Cette approche multiparamétrique de « Score d’Entropie » est testée dans une population pilote au moment des biopsies et présente des performances diagnostique pour sélectionner les lésions à biopsier. Ce score d’entropie participe de la stratification du cancer en corrélant positivement avec le score de Gleason et la longueur de cancer biopsique.La troisième partie explore le rôle de l’IRM dans le suivi d’une thérapie émergente, dite focale, du cancer. Il s’agit d’un travail de recalage non-rigide longitudinal sur une cohorte de patients traités par thérapie focale en vue de compenser les déformation focalement induites. Il apparaît que ce type de recalage peut permettre un suivi objectif des résultats d’ablation et potentiellement élaborer une cible biopsique et radiologique dans le suivi oncologique. / Conventional prostate MRI, enhanced by diffusion and perfusion sequences, and then named multiparametric, showed high performances for detection of prostate cancer using visual scoring. Indications in stratification, prognosis, treatment planning and follow up are currently under investigations.First part of this work attached itself to describe, elaborate and use a non-rigid image fusion method in 3D between gold standard histology of radical prostatectomy and MRI. Investigations captured the significant differences in shape and volume of in vivo and ex vivo prostate using MRI. The developed multimodality fusion method was applied to a cohort of patients who underwent MRI prior surgery. Results showed a stratified underestimation of cancer volume by MRI. Clinical output resides in detection, stratification and surgical planning.The second part proposed some texture analysis of sequences and quantitative maps. As a multiparametric approach, the Entropy Score is applied in a pilot cohort at time of biopsy and showed some potential usefulness to select MRI targets without compromising detection of significant cancer. By positively correlating with the Gleason Score and the maximal core length of cancer, Entropy Score participates of stratification of cancer.The third part explored application of image registration in the longitudinal follow up of an emergent therapy, said focal (FT). As a conservative approach, FT induces very local deformation of the gland which appears to be appropriately modelled by non-rigid registration, then opening possibilities to guide further control biopsy and radiologic assessment.

There is an emerging global epidemic of obesity and related complications, such as type 2diabetes (T2D). Alterations in body composition (adipose tissue, muscle volume and fatcontents) are known to be associated with an increased metabolic risk. Understanding of theunderlying mechanisms is key for development of novel intervention strategies. One study investigating the effect on body composition by different diets is Lipogain1. In this study, it was found that a small weight gain induced by polyunsaturated fats (PUFA, n=19) or saturated fats (SFA, n=20) had very different effects on body fat, liver fat and lean tissue mass respectively. The SFA group gained more liver fat and fat mass in general, while the PUFA group gained more muscle mass. These results were determined by magnetic resonance imaging.  The goal of this project was to visualize the results from Lipogain1 by utilizing the noveltechnique Imiomics. Imiomics is a method for statistical analysis of whole-body medical images. By utilizing image registration, all images are transformed to a common reference space. This enables point-wise comparisons between all images included in the analysis. In this project, mean images of the alterations in fat content and local volume change of the two groups were created. These were used to visualize the alterations in body composition from the study. Additionally, statistical tests were used to visualize statistically significant differences between the groups.  Differences between the groups could be seen in the mean images. Mainly a higher fat content increase was seen in SFA in comparison to PUFA. There was also a larger volume expansion in fat tissue in SFA than in PUFA, while PUFA instead had a larger volume expansion in muscles. An unexpected result was also found; the liver had expanded in PUFA but not in SFA. Unfortunately, few significant differences could be visualized between the groups when the statistical test was performed. The conclusion was that this method is promising for visualization of these kinds of studies, especially due to the potential of finding new, unexpected results. However, a somewhat larger cohort and possibly larger alterations in body composition might be needed to be able to visualize and quantify statistically significant differences between the groups on a voxel-wise level.

Shipping companies have a lot of difficulties to control and screen packages such as mail or different types of cargo that may contain dangerous or illegal goods. This project has the goal to enhance the supply chain security by elaborating a way to automatically detect manipulated packages. Based on image comparison, an algorithm can say whether a package shows significant doubts to be put aside for more inspection. After being coded, this algorithm is explained in this thesis. It uses an image registration method as well as a differentiation technique to detect tampered patterns from one image of package at one point of the supply chain to another image of the same package at a later stage. Results show that re-sealed packages, ripped packages or blacked labels can be detected and minor manipulations such as modifications on the barcode can be detected with a close-up of the local region. The principal goal of this project is to give recommendations on what is possible to detect and how to implement this algorithm. This work is a first step toward the use of image processing in future work for package screening.

As mobile phones get increasingly complicated the demands for an effective firmware update service increase. A proposed solution is Firmware Over The Air (FOTA) and the Open Mobile Alliance’s Device Management where mobile phones can be updated and managed via the mobile phone network. However, before these operations can be carried out, all FOTA capable mobile phones that should be served must be discovered and registered with a distributor of updates. The information provided must be sufficient to uniquely identify devices, initiate a Device Management session, and determine if a firmware update is needed. This thesis addresses the problems that a solution in automatically collecting this information. Several solutions are presented and their suitability evaluated on the basis of defined and analyzed requirements. The solutions most thoroughly examined are various manual solutions, retrieval of information from core network nodes, and utilizing the Short Message Service (SMS) or Unstructured Supplementary Service Data (USSD). A phone application has been implemented according to the requirements from the Chinese network operator China Mobile Communications Corporation (CMCC). It is a part of a solution in which the information is delivered via a SMS session. The design and development phase of the application is described, accompanied by a brief description of the Symbian OS and the working environment (tools, devices, etc.) needed to implement this solution. This work took place at the Sony Ericsson office in Beijing, China. The application implemented is robust and it is impossible to avoid registration, furthermore the user can not be exposed to acknowledgement messages. It has been made possible on the cost of decreased phone performance (a few kB of memory) since the application runs all the time. Malfunctioning phone or network may hinder registration. / Mobiltelefoner blir ständigt mer komplicerade vilket medför att efterfrågan av en effektiv lösning för uppdateringar av mjukvaran i mobiltelefonerna ökar. Lösningen är Firmware Over The Air (FOTA) och Device Management; mobiltelefonerna uppdateras och sköts via mobiltelefonnätverket. Men innan förfaranden kan exekveras måste alla mobiltelefoner med FOTA som ska omfattas av tjänsten upptäckas och registreras hos den som distribuerar uppdateringarna. Den information som måste levereras måste vara tillräcklig för att kunna identifiera mobiltelefonen, genomföra en Device Management session och avgöra om en uppdatering av mjukvaran är nödvändig. Detta examensarbete behandlar de problem som en lösning i vilken information tillhandahålls möter. Ett flertal lösningar presenteras och deras lämplighet utvärderas på basis av definierade och analyserade krav. De mest ingående undersökta lösningarna är olika manuella lösningar, insamling av information från noderna av kärnnätverket samt utnyttjande av SMS eller USSD. En telefonapplikation har implementeras enligt krav från den kinesiska operatören CMCC. Applikationen är en del av en lösning i vilken informationen levereras via en SMS-session. Applikationens design och utvecklingsfasen är beskriven, samt en översiktlig beskrivning av Symbian operativsystem och utvecklingsmiljön (verktyg, mobiltelefoner, etc.) som behövdes för att implementera lösningen. Detta arbete genomfördes på Sony Ericssons kontor i Beijing, Kina.

Image segmentation and image registration are two fundamental problems in computer vision and medical image processing. In image segmentation, one seeks to partition an image into meaningful segments by assigning a label to each pixel indicating which segment it belongs to. In image registration, one seeks to recover a spatial transformation that geometrically aligns two or more images, which allows downstream image analyses in which the registered images share a coordinate system. Image processing pipelines typically apply these procedures sequentially even though the segmentation of an image could improve its registration and registration of an image could improve its segmentation. With an appropriate parametrization, one can view these two tasks as an inference problem in which the spatial transformation and segmentation are latent variables. In this work, registration and segmentation are integrated through a hierarchical Bayesian generative framework. The framework models the data generating process of a set of magnetic resonance (MR) images of ischemic stroke lesioned brains. Under this framework, we simultaneously estimate a lesion tissue segmentation along with a spatial diffeomorphic transformation that maps a subject image into spatial correspondence with a healthy template image. The framework is evaluated on two-dimensional images both real and synthetic. Experimental results on real MR images show that simultaneous segmentation and registration can significantly improve the accuracy of lesion segmentation as well as the accuracy of registration near the lesion.