11 research outputs found

    Generative Models for Preprocessing of Hospital Brain Scans

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    I will in this thesis present novel computational methods for processing routine clinical brain scans. Such scans were originally acquired for qualitative assessment by trained radiologists, and present a number of difficulties for computational models, such as those within common neuroimaging analysis software. The overarching objective of this work is to enable efficient and fully automated analysis of large neuroimaging datasets, of the type currently present in many hospitals worldwide. The methods presented are based on probabilistic, generative models of the observed imaging data, and therefore rely on informative priors and realistic forward models. The first part of the thesis will present a model for image quality improvement, whose key component is a novel prior for multimodal datasets. I will demonstrate its effectiveness for super-resolving thick-sliced clinical MR scans and for denoising CT images and MR-based, multi-parametric mapping acquisitions. I will then show how the same prior can be used for within-subject, intermodal image registration, for more robustly registering large numbers of clinical scans. The second part of the thesis focusses on improved, automatic segmentation and spatial normalisation of routine clinical brain scans. I propose two extensions to a widely used segmentation technique. First, a method for this model to handle missing data, which allows me to predict entirely missing modalities from one, or a few, MR contrasts. Second, a principled way of combining the strengths of probabilistic, generative models with the unprecedented discriminative capability of deep learning. By introducing a convolutional neural network as a Markov random field prior, I can model nonlinear class interactions and learn these using backpropagation. I show that this model is robust to sequence and scanner variability. Finally, I show examples of fitting a population-level, generative model to various neuroimaging data, which can model, e.g., CT scans with haemorrhagic lesions

    Two and three dimensional segmentation of multimodal imagery

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    The role of segmentation in the realms of image understanding/analysis, computer vision, pattern recognition, remote sensing and medical imaging in recent years has been significantly augmented due to accelerated scientific advances made in the acquisition of image data. This low-level analysis protocol is critical to numerous applications, with the primary goal of expediting and improving the effectiveness of subsequent high-level operations by providing a condensed and pertinent representation of image information. In this research, we propose a novel unsupervised segmentation framework for facilitating meaningful segregation of 2-D/3-D image data across multiple modalities (color, remote-sensing and biomedical imaging) into non-overlapping partitions using several spatial-spectral attributes. Initially, our framework exploits the information obtained from detecting edges inherent in the data. To this effect, by using a vector gradient detection technique, pixels without edges are grouped and individually labeled to partition some initial portion of the input image content. Pixels that contain higher gradient densities are included by the dynamic generation of segments as the algorithm progresses to generate an initial region map. Subsequently, texture modeling is performed and the obtained gradient, texture and intensity information along with the aforementioned initial partition map are used to perform a multivariate refinement procedure, to fuse groups with similar characteristics yielding the final output segmentation. Experimental results obtained in comparison to published/state-of the-art segmentation techniques for color as well as multi/hyperspectral imagery, demonstrate the advantages of the proposed method. Furthermore, for the purpose of achieving improved computational efficiency we propose an extension of the aforestated methodology in a multi-resolution framework, demonstrated on color images. Finally, this research also encompasses a 3-D extension of the aforementioned algorithm demonstrated on medical (Magnetic Resonance Imaging / Computed Tomography) volumes

    Simplified inverse filter tracked affective acoustic signals classification incorporating deep convolutional neural networks

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    Facial expressions, verbal, behavioral, such as limb movements, and physiological features are vital ways for affective human interactions. Researchers have given machines the ability to recognize affective communication through the above modalities in the past decades. In addition to facial expressions, changes in the level of sound, strength, weakness, and turbulence will also convey affective. Extracting affective feature parameters from the acoustic signals have been widely applied in customer service, education, and the medical field. In this research, an improved AlexNet-based deep convolutional neural network (A-DCNN) is presented for acoustic signal recognition. Firstly, preprocessed on signals using simplified inverse filter tracking (SIFT) and short-time Fourier transform (STFT), Mel frequency Cepstrum (MFCC) and waveform-based segmentation were deployed to create the input for the deep neural network (DNN), which was applied widely in signals preprocess for most neural networks. Secondly, acoustic signals were acquired from the public Ryerson Audio-Visual Database of Affective Speech and Song (RAVDESS) affective speech audio system. Through the acoustic signal preprocessing tools, the basic features of the kind of sound signals were calculated and extracted. The proposed DNN based on improved AlexNet has a 95.88% accuracy on classifying eight affective of acoustic signals. By comparing with some linear classifications, such as decision table (DT) and Bayesian inference (BI) and other deep neural networks, such as AlexNet+SVM, recurrent convolutional neural network (R-CNN), etc., the proposed method achieves high effectiveness on the accuracy (A), sensitivity (S1), positive predictive (PP), and f1-score (F1). Acoustic signals affective recognition and classification can be potentially applied in industrial product design through measuring consumers’ affective responses to products; by collecting relevant affective sound data to understand the popularity of the product, and furthermore, to improve the product design and increase the market responsiveness

    Neuroinformatics in Functional Neuroimaging

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    This Ph.D. thesis proposes methods for information retrieval in functional neuroimaging through automatic computerized authority identification, and searching and cleaning in a neuroscience database. Authorities are found through cocitation analysis of the citation pattern among scientific articles. Based on data from a single scientific journal it is shown that multivariate analyses are able to determine group structure that is interpretable as particular “known ” subgroups in functional neuroimaging. Methods for text analysis are suggested that use a combination of content and links, in the form of the terms in scientific documents and scientific citations, respectively. These included context sensitive author ranking and automatic labeling of axes and groups in connection with multivariate analyses of link data. Talairach foci from the BrainMap ™ database are modeled with conditional probability density models useful for exploratory functional volumes modeling. A further application is shown with conditional outlier detection where abnormal entries in the BrainMap ™ database are spotted using kernel density modeling and the redundancy between anatomical labels and spatial Talairach coordinates. This represents a combination of simple term and spatial modeling. The specific outliers that were found in the BrainMap ™ database constituted among others: Entry errors, errors in the article and unusual terminology

    Deep Learning in Medical Image Analysis

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    The accelerating power of deep learning in diagnosing diseases will empower physicians and speed up decision making in clinical environments. Applications of modern medical instruments and digitalization of medical care have generated enormous amounts of medical images in recent years. In this big data arena, new deep learning methods and computational models for efficient data processing, analysis, and modeling of the generated data are crucially important for clinical applications and understanding the underlying biological process. This book presents and highlights novel algorithms, architectures, techniques, and applications of deep learning for medical image analysis

    Tätigkeitsbericht 2017-2019/20

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    STED Nanoscopy to Illuminate New Avenues in Cancer Research – From Live Cell Staining and Direct Imaging to Decisive Preclinical Insights for Diagnosis and Therapy

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    Molecular imaging is established as an indispensable tool in various areas of cancer research, ranging from basic cancer biology and preclinical research to clinical trials and medical practice. In particular, the field of fluorescence imaging has experienced exceptional progress during the last three decades with the development of various in vivo technologies. Within this field, fluorescence microscopy is primarily of experimental use since it is especially qualified for addressing the fundamental questions of molecular oncology. As stimulated emission depletion (STED) nanoscopy combines the highest spatial and temporal resolutions with live specimen compatibility, it is best-suited for real-time investigations of the differences in the molecular machineries of malignant and normal cells to eventually translate the acquired knowledge into increased diagnostic and therapeutic efficacy. This thesis presents the application of STED nanoscopy to two acute topics in cancer research of direct or indirect clinical interest. The first project has investigated the structure of telomeres, the ends of the linear eukaryotic chromosomes, in intact human cells at the nanoscale. To protect genome integrity, a telomere can mask the chromosome end by folding back and sequestering its single-stranded 3’-overhang in an upstream part of the double-stranded DNA repeat region. The formed t-loop structure has so far only been visualized by electron microscopy and fluorescence nanoscopy with cross-linked mammalian telomeric DNA after disruption of cell nuclei and spreading. For the first time, this work demonstrates the existence of t-loops within their endogenous nuclear environment in intact human cells. The identification of further telomere conformations has laid the groundwork for distinguishing cancerous cells that use different telomere maintenance mechanisms based on their individual telomere populations by a combined STED nanoscopy and deep learning approach. The population difference was essentially attributed to the promyelocytic leukemia (PML) protein that significantly perturbs the organization of a subpopulation of telomeres towards an open conformation in cancer cells that employ a telomerase-independent, alternative telomere lengthening mechanism. Elucidating the nanoscale topology of telomeres and associated proteins within the nucleus has provided new insight into telomere structure-function relationships relevant for understanding the deregulation of telomere maintenance in cancer cells. After understanding the molecular foundations, this newly gained knowledge can be exploited to develop novel or refined diagnostic and treatment strategies. The second project has characterized the intracellular distribution of recently developed prostate cancer tracers. These novel prostate-specific membrane antigen (PSMA) inhibitors have revolutionized the treatment regimen of prostate cancer by enabling targeted imaging and therapy approaches. However, the exact internalization mechanism and the subcellular fate of these tracers have remained elusive. By combining STED nanoscopy with a newly developed non-standard live cell staining protocol, this work confirmed cell surface clustering of the targeted membrane antigen upon PSMA inhibitor binding, subsequent clathrin-dependent endocytosis and endosomal trafficking of the antigen-inhibitor complex. PSMA inhibitors accumulate in prostate cancer cells at clinically relevant time points, but strikingly and in contrast to the targeted antigen itself, they eventually distribute homogenously in the cytosol. This project has revealed the subcellular fate of PSMA/PSMA inhibitor complexes for the first time and provides crucial knowledge for the future application of these tracers including the development of new strategies in the field of prostate cancer diagnostics and therapeutics. Relying on the photostability and biocompatibility of the applied fluorophores, the performance of live cell STED nanoscopy in the field of cancer research is boosted by the development of improved fluorophores. The third project in this thesis introduces a biocompatible, small molecule near-infrared dye suitable for live cell STED imaging. By the application of a halogen dance rearrangement, a dihalogenated fluorinatable pyridinyl rhodamine could be synthesized at high yield. The option of subsequent radiolabeling combined with excellent optical properties and a non-toxic profile renders this dye an appropriate candidate for medical and bioimaging applications. Providing an intrinsic and highly specific mitochondrial targeting ability, the radiolabeled analogue is suggested as a vehicle for multimodal (positron emission tomography and optical imaging) medical imaging of mitochondria for cancer diagnosis and therapeutic approaches in patients and biopsy tissue. The absence of cytotoxicity is not only a crucial prerequisite for clinically used fluorophores. To guarantee the generation of meaningful data mirroring biological reality, the absence of cytotoxicity is likewise a decisive property of dyes applied in live cell STED nanoscopy. The fourth project in this thesis proposes a universal approach for cytotoxicity testing based on characterizing the influence of the compound of interest on the proliferation behavior of human cell lines using digital holographic cytometry. By applying this approach to recently developed live cell STED compatible dyes, pronounced cytotoxic effects could be excluded. Looking more closely, some of the tested dyes slightly altered cell proliferation, so this project provides guidance on the right choice of dye for the least invasive live cell STED experiments. Ultimately, live cell STED data should be exploited to extract as much biological information as possible. However, some information might be partially hidden by image degradation due the dynamics of living samples and the deliberate choice of rather conservative imaging parameters in order to preserve sample viability. The fifth project in this thesis presents a novel image restoration method in a Bayesian framework that simultaneously performs deconvolution, denoising as well as super-resolution, to restore images suffering from noise with mixed Poisson-Gaussian statistics. Established deconvolution or denoising methods that consider only one type of noise generally do not perform well on images degraded significantly by mixed noise. The newly introduced method was validated with live cell STED telomere data proving that the method can compete with state-of-the-art approaches. Taken together, this thesis demonstrates the value of an integrated approach for STED nanoscopy imaging studies. A coordinated workflow including sample preparation, image acquisition and data analysis provided a reliable platform for deriving meaningful conclusions for current questions in the field of cancer research. Moreover, this thesis emphasizes the strength of iteratively adapting the individual components in the operational chain and it particularly points towards those components that, if further improved, optimize the significance of the final results rendering live cell STED nanoscopy even more powerful

    Humanoid Robots

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    For many years, the human being has been trying, in all ways, to recreate the complex mechanisms that form the human body. Such task is extremely complicated and the results are not totally satisfactory. However, with increasing technological advances based on theoretical and experimental researches, man gets, in a way, to copy or to imitate some systems of the human body. These researches not only intended to create humanoid robots, great part of them constituting autonomous systems, but also, in some way, to offer a higher knowledge of the systems that form the human body, objectifying possible applications in the technology of rehabilitation of human beings, gathering in a whole studies related not only to Robotics, but also to Biomechanics, Biomimmetics, Cybernetics, among other areas. This book presents a series of researches inspired by this ideal, carried through by various researchers worldwide, looking for to analyze and to discuss diverse subjects related to humanoid robots. The presented contributions explore aspects about robotic hands, learning, language, vision and locomotion

    [<sup>18</sup>F]fluorination of biorelevant arylboronic acid pinacol ester scaffolds synthesized by convergence techniques

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    Aim: The development of small molecules through convergent multicomponent reactions (MCR) has been boosted during the last decade due to the ability to synthesize, virtually without any side-products, numerous small drug-like molecules with several degrees of structural diversity.(1) The association of positron emission tomography (PET) labeling techniques in line with the “one-pot” development of biologically active compounds has the potential to become relevant not only for the evaluation and characterization of those MCR products through molecular imaging, but also to increase the library of radiotracers available. Therefore, since the [18F]fluorination of arylboronic acid pinacol ester derivatives tolerates electron-poor and electro-rich arenes and various functional groups,(2) the main goal of this research work was to achieve the 18F-radiolabeling of several different molecules synthesized through MCR. Materials and Methods: [18F]Fluorination of boronic acid pinacol esters was first extensively optimized using a benzaldehyde derivative in relation to the ideal amount of Cu(II) catalyst and precursor to be used, as well as the reaction solvent. Radiochemical conversion (RCC) yields were assessed by TLC-SG. The optimized radiolabeling conditions were subsequently applied to several structurally different MCR scaffolds comprising biologically relevant pharmacophores (e.g. β-lactam, morpholine, tetrazole, oxazole) that were synthesized to specifically contain a boronic acid pinacol ester group. Results: Radiolabeling with fluorine-18 was achieved with volumes (800 μl) and activities (≤ 2 GBq) compatible with most radiochemistry techniques and modules. In summary, an increase in the quantities of precursor or Cu(II) catalyst lead to higher conversion yields. An optimal amount of precursor (0.06 mmol) and Cu(OTf)2(py)4 (0.04 mmol) was defined for further reactions, with DMA being a preferential solvent over DMF. RCC yields from 15% to 76%, depending on the scaffold, were reproducibly achieved. Interestingly, it was noticed that the structure of the scaffolds, beyond the arylboronic acid, exerts some influence in the final RCC, with electron-withdrawing groups in the para position apparently enhancing the radiolabeling yield. Conclusion: The developed method with high RCC and reproducibility has the potential to be applied in line with MCR and also has a possibility to be incorporated in a later stage of this convergent “one-pot” synthesis strategy. Further studies are currently ongoing to apply this radiolabeling concept to fluorine-containing approved drugs whose boronic acid pinacol ester precursors can be synthesized through MCR (e.g. atorvastatin)

    Gaze-Based Human-Robot Interaction by the Brunswick Model

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    We present a new paradigm for human-robot interaction based on social signal processing, and in particular on the Brunswick model. Originally, the Brunswick model copes with face-to-face dyadic interaction, assuming that the interactants are communicating through a continuous exchange of non verbal social signals, in addition to the spoken messages. Social signals have to be interpreted, thanks to a proper recognition phase that considers visual and audio information. The Brunswick model allows to quantitatively evaluate the quality of the interaction using statistical tools which measure how effective is the recognition phase. In this paper we cast this theory when one of the interactants is a robot; in this case, the recognition phase performed by the robot and the human have to be revised w.r.t. the original model. The model is applied to Berrick, a recent open-source low-cost robotic head platform, where the gazing is the social signal to be considered
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