New MR imaging techniques in epilepsy

This thesis is concerned with the application of three magnetic resonance (MR) techniques in epilepsy: i.) Fluid attenuated inversion recovery prepared (FLAIR) imaging, ii.) diffusion imaging including diffusion tensor imaging (DTI) and iii.) serial and high resolution imaging of the hippocampus. I assessed the clinical value of fast FLAIR in epilepsy in a study involving 128 patients and of 3D FLAIR in a study involving 10 patients. The conspicuity of neocortical lesions and hippocampal sclerosis was increased. New lesions were detected in 5% of patients. The extent of low grade tumours was best assessed on 3D fast FLAIR images. Fast FLAIR was inferior to standard MR techniques for identifying and heterotopia. I applied newly developed, experimental diffusion imaging techniques. In eight studies using different diffusion imaging techniques involving a total of 50 patients and 54 control subjects I investigated the mobility of water molecules in the human epileptic brain in vivo. I used spin echo diffusion imaging in two studies, echo planar imaging (EPI) based DTI in four studies and EPI diffusion imaging in a patient during focal status epilepticus. Finally, in a preliminary study I attempted to use EPI diffusion imaging as a contrast to visualise transient changes associated with frequent lateralizing spikes. Our findings were: i.) diffusion is increased in hippocampal sclerosis suggesting a loss of structural organization and expansion of the extracellular space, ii.) displaying the directionality (anisotropy) of diffusion is superior to standard imaging to visualise tracts, iii.) anisotropy is reduced in the pyramidal tract in patients with hemiparesis and iv.) in the optic radiation in patients with hemianopia after temporal lobectomy suggesting wallerian degeneration, v.) both developmental and acquired structural abnormalities have a lower anisotropy than normal white matter, vi.) diffusion abnormalities in blunt head trauma are widespread and may include regions which are normal on standard imaging, indicating micro structural damage suggestive of diffuse axonal injury, vii.) focal status epilepticus can be associated with a reduced difflision in the affected cortex, viii.) diffusion imaging may be useful as a contrast for event-related (spike triggered) functional MR imaging. With serial MRI I demonstrated hippocampal volume loss in a patient after generalized status epilepticus and with high resolution imaging of an anatomical specimen and a control subject I showed hippocampal layers on MR images. The results presented in this thesis emphasised the flexibility of MR imaging and its ability to demonstrate abnormalities in vivo. FLAIR imaging is now part of the clinical work up of patients with epilepsy. Diffusion imaging has been shown to be superior to standard imaging to visualise tracts which has far-reaching implications for neurological applications. Diffusion imaging also provides an exciting window to study cerebral micro structure in vivo. Serial imaging allows for the first time the visualisation of temporal changes and high resolution imaging has the prospect of demonstrating hippocampal layers in vivo. MR imaging is a constantly progressing technique. It is hoped that this thesis will help to formulate hypotheses for new MR experiments to study the relationship of dysfunction and structural abnormalities

Local liquid velocity measurement of trickle bed reactor using digitial industrial X-ray radiography

Trickle Bed Reactors (TBRs) are fixed beds of particles in which both liquid and gas flow concurrently downward. They are widely used to produce not only fuels but also lubrication products. The measurement and the knowledge of local liquid velocities (VLL) in TBRs is less which is essential for advancing the understanding of its hydrodynamics and for validation computational fluid dynamics (CFD). Therefore, this work focused on developing a new, non-invasive, statistically reliable technique that can be used to measure local liquid velocity (VLL) in two-dimensions (2-D). This is performed by combining Digital Industrial X-ray Radiography (DIR) and Particle Tracking Velocimetry (PTV) techniques. This work also make possible the development of three-dimensional (3-D) VLL measurements that can be taken in TBRs. Measurements taken through both the combined and the novel technique, once validated, were found to be comparable to another technique (a two-point fiber optical probe) currently being developed at Missouri University of Science and Technology. The results from this study indicate that, for a gas-liquid-solid type bed, the measured VLL can have a maximum range that is between 35 and 51 times that of its superficial liquid velocity (VSL). Without the existence of gas, the measured VLL can have a maximum range that is between 4 and 4.7 times that of its VSL. At a higher VSL, the particle tracer was greatly distributed and became carried away by a high liquid flow rate. Neither the variance nor the range of measured VLL varied for any of the replications, confirming the reproducibility of the experimental measurements used, regardless of the VSL. The liquid\u27s movement inside the pore was consistent with findings from previous studies that used various techniques --Abstract, page iii

Skin temperature variations in the cold

Skin temperature plays an important role in human thermoregulation together with core temperature. Skin temperature varies to a large extent across the body and this is especially pronounced in cold environments. The variations of skin temperature are also involved in the generation of regional thermal perceptions that can lead to behavioural adjustments. Whilst the temporal and inter-individual variations of skin temperature have been well studied using contact sensors, the knowledge of spatial variations has received less attention in the literature. Infrared thermography is a specific imaging technique particularly valuable for the exploration of the topography or pattern of skin temperature across the body. Most research using this technique has only been case studies or experiments focused in one specific body region. However, extensive regional skin temperature data over the whole-body can be proven useful for different types of applications including the sport clothing industry in combination with other body-mapping data. The primary aim of this thesis was to develop an original and standardised method using infrared thermography enabling whole-body skin temperature data to be compared for the assessment of spatial, temporal and inter-individual variations. A specific methodology for infrared data collection and data processing was successfully developed in order to combine data from a variety of participants varying in anthropometrical characteristics. The main outcomes were the production of several skin temperature body maps, either absolute maps to show the magnitude of the temporal or inter-individual effects, and normalised maps (relative to mean skin temperature) allowing for topographical comparisons between protocol stages, populations or interventions. The second aim of the thesis was to extend the understanding of the skin temperature patterns and how these could relate with thermal perceptions. The body-mapping method gave the opportunity to investigate a large amount of conditions, where various internal or external determinants of skin temperature were be involved. This was mainly done in cool to cold environments (5°C to 20°C) where skin temperature is not uniform but is associated with local and overall comfort. Studies were firstly performed in semi-nude conditions (Chapter 3, 4, 5) and then in clothed conditions (Chapter 6 and 7). The semi-nude studies were designed to explore the potential sexdifferences in regional skin temperature responses whilst running (Chapter 3) with a special interest in the role of skinfold thickness, this was further extended with a group of males at rest having a large variety of fat content and thickness (Chapter 4). The influence of exercise type and air temperature on skin temperature patterns was studied with a rowing exercise (Chapter 5). Studies were then performed in clothed conditions (Chapter 5, 6). The influence of real-life conditions on skin temperature patterns and associated perceptual responses was observed during a hiking scenario (Chapter 6). Following these descriptive studies, manipulation of skin temperature patterns was performed using clothing in order to determine the presence of any relevant effect on thermal comfort (Chapter 7). Our results demonstrated that the skin temperature pattern over the whole-body is relatively universal with several features being consistently found regardless of the conditions or the populations. The upper body is usually warmer than the lower body and the body creases (orbital, elbow regions etc.) are also warmer than surrounding regions. A Y-shape of colder temperatures has been highlighted over the anterior torso as well as a T- or Y-shape of warmer temperature over the posterior torso. There are yet some specificities that can be displayed due to active muscles during exercise such as the warmer skin overlying the trapezius and biceps muscles in rowing (Chapter 5), the influence of the backpack construction with up to 3°C warmer skin temperature in the lower back (Chapter 6) or the importance of additional clothing insulation minimizing the anterior Y-shape of colder skin temperatures (Chapter 7). Beyond the thermal patterns, absolute skin temperature differences have been observed between sexes with females displaying 2°C colder skin during semi-nude running (Chapter 3) and 1°C colder skin during clothed walking (Chapter 6)compared to males. The skin temperature difference can also be as large as 6°C colder skin for an obese male compared to a very lean male (40% vs 7% body fat). Despite these differences, there were almost no significant differences in overall and regional thermal sensations and comfort between sexes or between males with varying body fat. Our results focused on body fat revealed that overall fat content and sum of skinfolds was inversely associated with the mean skin temperature response during various protocols (Chapter 4, 6, 7). Local skinfold thickness explained the inter-individual variability of local skin temperature for resting (Chapter 4) and exercising males (Chapter 7) in most body regions. In terms of intra-individual variations, the distribution of skinfold thickness across the anterior torso explained the distribution of skin temperature in this segment solely in conditions with strong regional contrasts (Chapter 3, 4 and 7). When the whole-body skin temperature pattern is considered, our body-mapping approach failed to show relationships between skin temperature distribution across the body and regional skinfold thickness distribution neither at rest nor during exercise. The relative contribution of other internal determinants such as local heat production,local blood flow distribution and local anthropometry should be further investigated to fully elucidate the spatial skin temperature variations depending on the climate, clothing and the body thermal state. Lastly, there was a trend towards improved thermal comfort during rest and exercise in the cold through a manipulation of skin temperature patterns targeting the naturally cold body regions with high insulation, therefore obtaining a more homogeneous skin temperature distribution across the body (Chapter 7). The present work will benefit the sport goods industry. The descriptive results of skin temperature variations will be useful in order to validate multi-segmental model of human thermoregulation. Further work can include pattern predictions for exercise types and conditions not covered by the present thesis. The skin temperature maps will mainly feed the general body-mapping approach for clothing design taking into account several other body mapping data such as sweat mapping and the combination of cold, warm and wetness sensitivity mappings. Lastly, the present results have highlighted the interest for targeted solutions and also the need for more evolutive systems in the field of cold weather apparel

Spatio-temporal evolution of interictal epileptic activity : a study with unaveraged multichannel MEG data in association with MRIs.

This thesis addresses issues relating to MEG modelling, analysis and interpretation of results. A source model employing current density distributions, namely Magnetic Field Tomography (MET), is used to obtain the MEG results. The first issue of concern refers to the registration of MEG data with structural MR images in an attempt to improve the localisation capability of MEG/MET. Simulations testing some spatial and tem poral aspects of the reconstruction capability of MET are also provided. A novel way of conducting MET studies in depth is suggested and implemented: the iterative use of a source space designed to cover deep situated structures on either side of the brain. The main bulk of this thesis is concerned with research into interictal epileptic activity as recorded by means of multichannel MEG system s and analysed using MET. The major aim is to investigate whether or not MET analysis of unaveraged MEG data (single epochs) is feasible in cases of pathophysiological signals and more specifically interictal signals from patients with epilepsy of a complex partial type. The investigation is undertaken against the "traditional" view of the impropriety and absurdity of using single epoch records in the MEG analysis due to noise dominance; we provide evidence that analysis of single, unaveraged epileptic spikes is actually feasible: we demonstrate spatio-temporal coherence in the MET results of the various single interictal events and show that activity extracted from the "averaged event" is made up of activity contributions which occur intermittently and at variable latencies. Our statements are drawn from the study of both superficial and deep activity

Diffeomorphic image registration with applications to deformation modelling between multiple data sets

Over last years, the diffeomorphic image registration algorithms have been successfully introduced into the field of the medical image analysis. At the same time, the particular usability of these techniques, in majority derived from the solid mathematical background, has been only quantitatively explored for the limited applications such as longitudinal studies on treatment quality, or diseases progression. The thesis considers the deformable image registration algorithms, seeking out those that maintain the medical correctness of the estimated dense deformation fields in terms of the preservation of the object and its neighbourhood topology, offer the reasonable computational complexity to satisfy time restrictions coming from the potential applications, and are able to cope with low quality data typically encountered in Adaptive Radiotherapy (ART). The research has led to the main emphasis being laid on the diffeomorphic image registration to achieve one-to-one mapping between images. This involves introduction of the log-domain parameterisation of the deformation field by its approximation via a stationary velocity field. A quantitative and qualitative examination of existing and newly proposed algorithms for pairwise deformable image registration presented in this thesis, shows that the log-Euclidean parameterisation can be successfully utilised in the biomedical applications. Although algorithms utilising the log-domain parameterisation have theoretical justification for maintaining diffeomorphism, in general, the deformation fields produced by them have similar properties as these estimated by classical methods. Having this in mind, the best compromise in terms of the quality of the deformation fields has been found for the consistent image registration framework. The experimental results suggest also that the image registration with the symmetrical warping of the input images outperforms the classical approaches, and simultaneously can be easily introduced to most known algorithms. Furthermore, the log-domain implicit group-wise image registration is proposed. By linking the various sets of images related to the different subjects, the proposed image registration approach establishes a common subject space and between-subject correspondences therein. Although the correspondences between groups of images can be found by performing the classic image registration, the reference image selection (not required in the proposed implementation), may lead to a biased mean image being estimated and the corresponding common subject space not adequate to represent the general properties of the data sets. The approaches to diffeomorphic image registration have been also utilised as the principal elements for estimating the movements of the organs in the pelvic area based on the dense deformation field prediction system driven by the partial information coming from the specific type of the measurements parameterised using the implicit surface representation, and recognising facial expressions where the stationary velocity fields are used as the facial expression descriptors. Both applications have been extensively evaluated based on the real representative data sets of three-dimensional volumes and two-dimensional images, and the obtained results indicate the practical usability of the proposed techniques

Object Recognition

Vision-based object recognition tasks are very familiar in our everyday activities, such as driving our car in the correct lane. We do these tasks effortlessly in real-time. In the last decades, with the advancement of computer technology, researchers and application developers are trying to mimic the human's capability of visually recognising. Such capability will allow machine to free human from boring or dangerous jobs

Similarity, Retrieval, and Classification of Motion Capture Data

Three-dimensional motion capture data is a digital representation of the complex spatio-temporal structure of human motion. Mocap data is widely used for the synthesis of realistic computer-generated characters in data-driven computer animation and also plays an important role in motion analysis tasks such as activity recognition. Both for efficiency and cost reasons, methods for the reuse of large collections of motion clips are gaining in importance in the field of computer animation. Here, an active field of research is the application of morphing and blending techniques for the creation of new, realistic motions from prerecorded motion clips. This requires the identification and extraction of logically related motions scattered within some data set. Such content-based retrieval of motion capture data, which is a central topic of this thesis, constitutes a difficult problem due to possible spatio-temporal deformations between logically related motions. Recent approaches to motion retrieval apply techniques such as dynamic time warping, which, however, are not applicable to large data sets due to their quadratic space and time complexity. In our approach, we introduce various kinds of relational features describing boolean geometric relations between specified body points and show how these features induce a temporal segmentation of motion capture data streams. By incorporating spatio-temporal invariance into the relational features and induced segments, we are able to adopt indexing methods allowing for flexible and efficient content-based retrieval in large motion capture databases. As a further application of relational motion features, a new method for fully automatic motion classification and retrieval is presented. We introduce the concept of motion templates (MTs), by which the spatio-temporal characteristics of an entire motion class can be learned from training data, yielding an explicit, compact matrix representation. The resulting class MT has a direct, semantic interpretation, and it can be manually edited, mixed, combined with other MTs, extended, and restricted. Furthermore, a class MT exhibits the characteristic as well as the variational aspects of the underlying motion class at a semantically high level. Classification is then performed by comparing a set of precomputed class MTs with unknown motion data and labeling matching portions with the respective motion class label. Here, the crucial point is that the variational (hence uncharacteristic) motion aspects encoded in the class MT are automatically masked out in the comparison, which can be thought of as locally adaptive feature selection

Endoscopic Fluorescence Imaging:Spectral Optimization and in vivo Characterization of Positive Sites by Magnifying Vascular Imaging

Since several decades, the physicians are able to access hollow organs with endoscopic methods, which serve both as diagnostic and surgical means in a wide range of disciplines of the modern medicine (e.g. urology, pneumology, gastroenterology). Unfortunately, white light (WL) endoscopy displays a limited sensitivity to early pre-cancerous lesions. Hence, several endoscopic methods based on fluorescence imaging have been developed to overcome this limitation. Both endogenous and exogenously-induced fluorescence have been investigated, leading to commercial products. Indeed, autofluorescence bronchoscopy, as well as porphyrin-based fluorescence cystoscopy, are now on the market. As a matter of fact, fluorescence-based endoscopic detection methods show very high sensitivity to pre-cancerous lesions, which are often overlooked in WL endoscopy, but they still lack specificity mainly due to the high false-positive rate. Although most of these false positives can easily be rejected under WL observation, tissue abnormalities such as inflammations, hyperplasia, and metaplasia are more difficult to identify, often resulting in supplementary biopsies. Therefore, the purpose of this thesis is to study novel, fast, and convenient method to characterize fluorescence positive spots in situ during fluorescence endoscopy and, more generally, to optimize the existing endoscopic setup. In this thesis, several clinical evaluations were conducted either in the tracheo-bronchial tree and the urinary bladder. In the urinary bladder, fluorescence imaging for detection of non-muscle invasive bladder cancer is based on the selective production and accumulation of fluorescing porphyrins, mainly protoporphyrin IX (PpIX), in cancerous tissues after the instillation of Hexvix® during one hour. In this thesis, we adapted a rigid cystoscope to perform high magnification (HM) cystoscopy in order to discriminate false from true fluorescence positive findings. Both white light and fluorescence modes are possible with the magnification cystoscope, allowing observation of the bladder wall with magnification ranging between 30× – for standard observation – and 650×. The optical zooming setup allows adjusting the magnification continuously in situ. In the high magnification regime, the smallest diameter of the field of view is 600 microns and the resolution is 2.5 microns, when in contact with the bladder wall. With this HM cystoscope, we characterized the superficial vascularization of the fluorescing sites in WL (370–700 nm) reflectance imaging in order to discriminate cancerous from non-cancerous tissues. This procedure allowed us to establish a classification based on observed vascular patterns. 72 patients subject to Hexvix® f luorescence cystoscopy were included in the study. Comparison of HM cystoscopy classification with histopathology results confirmed 32/33 (97%) cancerous biopsies, and rejected 17/20 (85%) non-cancerous lesions. No vascular alteration could be observed on the only positive lesion that was negative in HM mode, probably because this sarcomatoid carcinoma was not originating in the bladder mucosa. We established with this study that a magnification ranging between 80× and 100× is an optimal tradeoff to perform both macroscopic PDD and HM reflectance imaging. In order to make this approach more quantitative, different algorithms of image processing (vessel segmentation and skeletonisation, global information extraction) were also implemented in this thesis. In order to better visualize the vessels, we improved their contrast with respect to the background. Since hemoglobin is a very strong absorber, we targeted the two hemoglobin absorption peaks by placing appropriate bandpass filters (blue 405±50 nm, green 550±50 nm) in the light source. HM cystoscopy was then performed sequentially with WL, blue and green illumination. The two latter showed higher vessel-to-background contrast, identifying different layers of vascularization due to the light penetration depth. During fluorescence cystoscopy, we often observed that the images are somehow "blurred" by a greenish screen between endoscope tip and bladder mucosa. Since this effect is enhanced by the urine production, it is more visible with flexible scopes (lower flushing capabilities) and imaging systems that collect only autofluorescence as background. Indeed, when the bladder is not flushed regularly, greenish flows coming out of the ureters can easily be observed. For this reason, it is supposed that some fluorophores contained in the urine are excited by the photodetection excitation light, and appear greenish on the screen. This effect may impair the visualization of the bladder mucosa, and thus cancerous lesions, and lowers sensitivity of the fluorescence cystoscopy. In this thesis, we identified the main metabolites responsible for the liquid fluorescence, and optimized the spectral design accordingly. In the tracheo-bronchial tree, the fluorescence contrast is based on the sharp autofluorescence (AF) decrease on early cancerous lesions in the green spectral region (around 500 nm) and a relatively less important decrease in the red spectral region (> 600 nm) when excited with blue-violet light (around 410 nm). It has been shown over the last years, that this contrast may be attributed to a combined effect of epithelium thickening and higher concentration of hemoglobin in the tissues underneath the (pre-)cancerous lesions. In this thesis, we contributed to the definition of the input design of several new prototypes, that were subsequently tested in the clinical environment. We first showed that narrow-band excitation in the blue-violet could increase the tumor-to-normal spectral contrast in the green spectral region. Then, we quantified the intra- and inter-patient variations in the AF intensities in order to optimize the spectral response of the endoscopic fluorescence imaging system. For this purpose, we developed an endoscopic reference to be placed close to the bronchial mucosa during bronchoscopy. Finally, we evaluated a novel AF bronchoscope with blue-backscattered light on 144 patients. This new device showed increased sensitivity for pre-neoplastic lesions. Similar to what we observed in the bladder, it is likely that developing new imaging capabilities (including vascular imaging) will facilitate discriminating true from false positive in AF bronchoscopy. Here, we demonstrated that this magnification allowed us to resolve vessels with a diameter of about 30 µm. This resolution is likely to be sufficient to identify Shibuya's vascular criteria (loops, meshes, dotted vessels) on AF positive lesions. This criteria allow him to recognize pre-cancerous lesions, and thus can potentially decrease the false-positive rate with our AF imaging system. This magnification was also showed to be better for routine bronchoscopy, since it delivers sharper and more structured images to the operator