Motion Segmentation Aided Super Resolution Image Reconstruction

This dissertation addresses Super Resolution (SR) Image Reconstruction focusing on motion segmentation. The main thrust is Information Complexity guided Gaussian Mixture Models (GMMs) for Statistical Background Modeling. In the process of developing our framework we also focus on two other topics; motion trajectories estimation toward global and local scene change detections and image reconstruction to have high resolution (HR) representations of the moving regions. Such a framework is used for dynamic scene understanding and recognition of individuals and threats with the help of the image sequences recorded with either stationary or non-stationary camera systems. We introduce a new technique called Information Complexity guided Statistical Background Modeling. Thus, we successfully employ GMMs, which are optimal with respect to information complexity criteria. Moving objects are segmented out through background subtraction which utilizes the computed background model. This technique produces superior results to competing background modeling strategies. The state-of-the-art SR Image Reconstruction studies combine the information from a set of unremarkably different low resolution (LR) images of static scene to construct an HR representation. The crucial challenge not handled in these studies is accumulating the corresponding information from highly displaced moving objects. In this aspect, a framework of SR Image Reconstruction of the moving objects with such high level of displacements is developed. Our assumption is that LR images are different from each other due to local motion of the objects and the global motion of the scene imposed by non-stationary imaging system. Contrary to traditional SR approaches, we employed several steps. These steps are; the suppression of the global motion, motion segmentation accompanied by background subtraction to extract moving objects, suppression of the local motion of the segmented out regions, and super-resolving accumulated information coming from moving objects rather than the whole scene. This results in a reliable offline SR Image Reconstruction tool which handles several types of dynamic scene changes, compensates the impacts of camera systems, and provides data redundancy through removing the background. The framework proved to be superior to the state-of-the-art algorithms which put no significant effort toward dynamic scene representation of non-stationary camera systems

MINFLUX Nanoscopy with Interferometric Approach

Single molecule tracking is an indispensable tool in life sciences due to its unmatched potential to observe and investigate functional dynamics of (macro)molecular machineries in living cells in a minimally invasive manner. The limiting factor for the spatio-temporal resolution of such studies is typically the finite photon emission rate of fluorescent single molecules. This work assesses to which extent the remarkable localization efficiency of MINFLUX nanoscopy allows for a higher spatio-temporal resolution than conventional super-resolution tracking approaches to reveal previously unresolvable subcellular dynamics. To this end, the phase scanner, an innovative scanning device was designed and built. It allows to interferometrically generate and scan various point spread functions by electrooptically controlling the phase shift between mutually coherent beamlets arranged in the back focal plane of a microscope objective. MINFLUX localizations were recorded that outperform the spatio-temporal resolution of an idealized camera-based localization by more than a factor of six. The unprecedented performance of the presented MINFLUX microscope was demonstrated by tracking Kinesin-1 motor proteins for the first time under physiological conditions in a single molecule tracking study. With these results, MINFLUX emerges as the most powerful technique when the highest spatio-temporal resolution is required in single molecule tracking studies

Multimodal image analysis of the human brain

Gedurende de laatste decennia heeft de snelle ontwikkeling van multi-modale en niet-invasieve hersenbeeldvorming technologieën een revolutie teweeg gebracht in de mogelijkheid om de structuur en functionaliteit van de hersens te bestuderen. Er is grote vooruitgang geboekt in het beoordelen van hersenschade door gebruik te maken van Magnetic Reconance Imaging (MRI), terwijl Elektroencefalografie (EEG) beschouwd wordt als de gouden standaard voor diagnose van neurologische afwijkingen. In deze thesis focussen we op de ontwikkeling van nieuwe technieken voor multi-modale beeldanalyse van het menselijke brein, waaronder MRI segmentatie en EEG bronlokalisatie. Hierdoor voegen we theorie en praktijk samen waarbij we focussen op twee medische applicaties: (1) automatische 3D MRI segmentatie van de volwassen hersens en (2) multi-modale EEG-MRI data analyse van de hersens van een pasgeborene met perinatale hersenschade. We besteden veel aandacht aan de verbetering en ontwikkeling van nieuwe methoden voor accurate en ruisrobuuste beeldsegmentatie, dewelke daarna succesvol gebruikt worden voor de segmentatie van hersens in MRI van zowel volwassen als pasgeborenen. Daarenboven ontwikkelden we een geïntegreerd multi-modaal methode voor de EEG bronlokalisatie in de hersenen van een pasgeborene. Deze lokalisatie wordt gebruikt voor de vergelijkende studie tussen een EEG aanval bij pasgeborenen en acute perinatale hersenletsels zichtbaar in MRI

Multidimensional embedded MEMS motion detectors for wearable mechanocardiography and 4D medical imaging

Background: Cardiovascular diseases are the number one cause of death. Of these deaths, almost 80% are due to coronary artery disease (CAD) and cerebrovascular disease. Multidimensional microelectromechanical systems (MEMS) sensors allow measuring the mechanical movement of the heart muscle offering an entirely new and innovative solution to evaluate cardiac rhythm and function. Recent advances in miniaturized motion sensors present an exciting opportunity to study novel device-driven and functional motion detection systems in the areas of both cardiac monitoring and biomedical imaging, for example, in computed tomography (CT) and positron emission tomography (PET). Methods: This Ph.D. work describes a new cardiac motion detection paradigm and measurement technology based on multimodal measuring tools — by tracking the heart’s kinetic activity using micro-sized MEMS sensors — and novel computational approaches — by deploying signal processing and machine learning techniques—for detecting cardiac pathological disorders. In particular, this study focuses on the capability of joint gyrocardiography (GCG) and seismocardiography (SCG) techniques that constitute the mechanocardiography (MCG) concept representing the mechanical characteristics of the cardiac precordial surface vibrations. Results: Experimental analyses showed that integrating multisource sensory data resulted in precise estimation of heart rate with an accuracy of 99% (healthy, n=29), detection of heart arrhythmia (n=435) with an accuracy of 95-97%, ischemic disease indication with approximately 75% accuracy (n=22), as well as significantly improved quality of four-dimensional (4D) cardiac PET images by eliminating motion related inaccuracies using MEMS dual gating approach. Tissue Doppler imaging (TDI) analysis of GCG (healthy, n=9) showed promising results for measuring the cardiac timing intervals and myocardial deformation changes. Conclusion: The findings of this study demonstrate clinical potential of MEMS motion sensors in cardiology that may facilitate in time diagnosis of cardiac abnormalities. Multidimensional MCG can effectively contribute to detecting atrial fibrillation (AFib), myocardial infarction (MI), and CAD. Additionally, MEMS motion sensing improves the reliability and quality of cardiac PET imaging.Moniulotteisten sulautettujen MEMS-liiketunnistimien käyttö sydänkardiografiassa sekä lääketieteellisessä 4D-kuvantamisessa Tausta: Sydän- ja verisuonitaudit ovat yleisin kuolinsyy. Näistä kuolemantapauksista lähes 80% johtuu sepelvaltimotaudista (CAD) ja aivoverenkierron häiriöistä. Moniulotteiset mikroelektromekaaniset järjestelmät (MEMS) mahdollistavat sydänlihaksen mekaanisen liikkeen mittaamisen, mikä puolestaan tarjoaa täysin uudenlaisen ja innovatiivisen ratkaisun sydämen rytmin ja toiminnan arvioimiseksi. Viimeaikaiset teknologiset edistysaskeleet mahdollistavat uusien pienikokoisten liiketunnistusjärjestelmien käyttämisen sydämen toiminnan tutkimuksessa sekä lääketieteellisen kuvantamisen, kuten esimerkiksi tietokonetomografian (CT) ja positroniemissiotomografian (PET), tarkkuuden parantamisessa. Menetelmät: Tämä väitöskirjatyö esittelee uuden sydämen kineettisen toiminnan mittaustekniikan, joka pohjautuu MEMS-anturien käyttöön. Uudet laskennalliset lähestymistavat, jotka perustuvat signaalinkäsittelyyn ja koneoppimiseen, mahdollistavat sydämen patologisten häiriöiden havaitsemisen MEMS-antureista saatavista signaaleista. Tässä tutkimuksessa keskitytään erityisesti mekanokardiografiaan (MCG), joihin kuuluvat gyrokardiografia (GCG) ja seismokardiografia (SCG). Näiden tekniikoiden avulla voidaan mitata kardiorespiratorisen järjestelmän mekaanisia ominaisuuksia. Tulokset: Kokeelliset analyysit osoittivat, että integroimalla usean sensorin dataa voidaan mitata syketiheyttä 99% (terveillä n=29) tarkkuudella, havaita sydämen rytmihäiriöt (n=435) 95-97%, tarkkuudella, sekä havaita iskeeminen sairaus noin 75% tarkkuudella (n=22). Lisäksi MEMS-kaksoistahdistuksen avulla voidaan parantaa sydämen 4D PET-kuvan laatua, kun liikeepätarkkuudet voidaan eliminoida paremmin. Doppler-kuvantamisessa (TDI, Tissue Doppler Imaging) GCG-analyysi (terveillä, n=9) osoitti lupaavia tuloksia sydänsykkeen ajoituksen ja intervallien sekä sydänlihasmuutosten mittaamisessa. Päätelmä: Tämän tutkimuksen tulokset osoittavat, että kardiologisilla MEMS-liikeantureilla on kliinistä potentiaalia sydämen toiminnallisten poikkeavuuksien diagnostisoinnissa. Moniuloitteinen MCG voi edistää eteisvärinän (AFib), sydäninfarktin (MI) ja CAD:n havaitsemista. Lisäksi MEMS-liiketunnistus parantaa sydämen PET-kuvantamisen luotettavuutta ja laatua

Single molecule tracking with light sheet microscopy

The work presented here concentrates on light sheet based fluorescence microscopy (LSFM) and its application to single molecule tracking. In LSFM the sample is illuminated perpendicular to the detection axis with a thin light sheet. In this manner a simple optical sectioning microscope is created, because only the focal plane of the detection optics is illuminated and no out-of-focus fluorescence is generated. This results in an enhancement of the signal-to-noise-ratio and combined with the high acquisition speed of a video microscopy a powerful tool is created to study single molecule dynamics on a millisecond timescale, A completely new setup was designed and constructed, that combines light sheet illumination technique with single molecule detection ability. Theoretical calculations and quantitative measurements of the illumination light sheet thickness (2-3 µm thick) and the microscope point spread function were performed. A direct comparison of LSFM and epi-illumination of model samples with intrinsic background fluorescence illustrated the clear contrast improvement of LSFM for thick samples. Single molecule detection is limited by the number of photons emitted by a single fluorophore per observation time. So, the ability to track single molecules is dependent on molecule speed, background, detection sensitivity and frame rate. The imaging speed with the concomitant high signal-to-noise ratio that could be realized within the setup was unprecedented until then. It permitted the observation of single protein trajectories in aqueous solution with a diffusion coefficient greater than 100 µm²/s. The in vivo imaging of single molecules in thick biological samples was demonstrated in living salivary gland cell nuclei of Chironomus tentans larvae. These cell nuclei afford exceptional possibilities for the study of RNA mobility, but provide a microscopic challenge with a diameter of 50-75 µm and up 200 µm deep within the sample. To image the intranuclear mobility of individual messenger RNA particles, they were indirectly labeled via the fluorescently labeled RNA binding protein hrp36. Thus it was possible to identify at least three different diffusion modes of the mRNA particles and indirectly measure the nuclear viscosity. A high flexibility and easy adaptation of the optical sectioning thickness is required to visualize biological samples of various sizes. Often, however, the sheet geometry is fixed, whereas it would be advantageous to adjust the sheet geometry to specimens of different dimensions. Therefore, an afocal cylindrical zoom lens system comprising only 5 lenses and a total system length of less than 160 mm was developed. Two movable optical elements were directly coupled, so that the zoom factor could be adjusted from 1x to 6.3x by a single motor. Polytene chromosomes of salivary gland cell nuclei of C.tentans larvae were imaged in vivo to demonstrate the advantages in image contrast by imaging with different light sheet dimensions. The light sheet microscope introduced in this thesis proofed its suitability for in vivo single molecule imaging deep within a biological sample. It has the potential to reveal new dynamic single molecule interactions in vivo and enables new studies and experiments of intracellular processes

Self-similarity and wavelet forms for the compression of still image and video data

This thesis is concerned with the methods used to reduce the data volume required to represent still images and video sequences. The number of disparate still image and video coding methods increases almost daily. Recently, two new strategies have emerged and have stimulated widespread research. These are the fractal method and the wavelet transform. In this thesis, it will be argued that the two methods share a common principle: that of self-similarity. The two will be related concretely via an image coding algorithm which combines the two, normally disparate, strategies. The wavelet transform is an orientation selective transform. It will be shown that the selectivity of the conventional transform is not sufficient to allow exploitation of self-similarity while keeping computational cost low. To address this, a new wavelet transform is presented which allows for greater orientation selectivity, while maintaining the orthogonality and data volume of the conventional wavelet transform. Many designs for vector quantizers have been published recently and another is added to the gamut by this work. The tree structured vector quantizer presented here is on-line and self structuring, requiring no distinct training phase. Combining these into a still image data compression system produces results which are among the best that have been published to date. An extension of the two dimensional wavelet transform to encompass the time dimension is straightforward and this work attempts to extrapolate some of its properties into three dimensions. The vector quantizer is then applied to three dimensional image data to produce a video coding system which, while not optimal, produces very encouraging results

Advances in Analysis and Exploration in Medical Imaging

With an ever increasing life expectancy, we see a concomitant increase in diseases capable of disrupting normal cognitive processes. Their diagnoses are difficult, and occur usually after daily living activities have already been compromised. This dissertation proposes machine learning methods for the study of the neurological implications of brain lesions. It addresses the analysis and exploration of medical imaging data, with particular emphasis to (f)MRI. Two main research directions are proposed. In the first, a brain tissue segmentation approach is detailed. In the second, a document mining framework, applied to reports of neuroscientific studies, is described. Both directions are based on retrieving consistent information from multi-modal data. A contribution in this dissertation is the application of a semi-supervised method, discriminative clustering, to identify different brain tissues and their partial volume information. The proposed method relies on variations of tissue distributions in multi-spectral MRI, and reduces the need for a priori information. This methodology was successfully applied to the study of multiple sclerosis and age related white matter diseases. It was also showed that early-stage changes of normal-appearing brain tissue can already predict decline in certain cognitive processes. Another contribution in this dissertation is in neuroscience meta-research. One limitation in neuroimage processing relates to data availability. Through document mining of neuroscientific reports, using images as source of information, one can harvest research results dealing with brain lesions. The context of such results can be extracted from textual information, allowing for an intelligent categorisation of images. This dissertation proposes new principles, and a combination of several techniques to the study of published fMRI reports. These principles are based on a number of distance measures, to compare various brain activity sites. Application to studies of the default mode network validated the proposed approach. The aforementioned methodologies rely on clustering approaches. When dealing with such strategies, most results depend on the choice of initialisation and parameter settings. By defining distance measures that search for clusters of consistent elements, one can estimate a degree of reliability for each data grouping. In this dissertation, it is shown that such principles can be applied to multiple runs of various clustering algorithms, allowing for a more robust estimation of data agglomeration