Segmentation, Reconstruction, and Analysis of Blood Thrombus Formation in 3D 2-Photon Microscopy Images

We study the problem of segmenting, reconstructing, and analyzing the structure growth of thrombi (clots) in blood vessels in vivo based on 2-photon microscopic image data. First, we develop an algorithm for segmenting clots in 3D microscopic images based on density-based clustering and methods for dealing with imaging artifacts. Next, we apply the union-of-balls (or alpha-shape) algorithm to reconstruct the boundary of clots in 3D. Finally, we perform experimental studies and analysis on the reconstructed clots and obtain quantitative data of thrombus growth and structures. We conduct experiments on laser-induced injuries in vessels of two types of mice (the wild type and the type with low levels of coagulation factor VII) and analyze and compare the developing clot structures based on their reconstructed clots from image data. The results we obtain are of biomedical significance. Our quantitative analysis of the clot composition leads to better understanding of the thrombus development, and is valuable to the modeling and verification of computational simulation of thrombogenesis

Ekstraksi Objek Pada Citra Radar FM-CW Dengan Metode DBSCAN

Makalah ini membahas rancang bangun dan implementasi ekstraksi objek pada radar FM-CW untuk mengatasi permasalahan kualitas citra yang ditangkap oleh radar. Teknik clustering density based spatial clustering of applications with noise (DBSCAN) digunakan untuk mengekstraksi objek dari data input. Hasil dari penelitian ini adalah rancang bangun ekstrasi objek dengan nilai minPts sebesar 4 dan nilai eps sebesar 4 sebagai parameter input untuk DBSCAN. Hasil dari rancang bangun ekstraksi objek adalah titik-titik data hasil ekstraksi objek yang lebih sederhana yang mampu mengatasi permasalahan kualitas citra yang ditangkap oleh radar. Selain itu, titik-titik data yang dihasilkan juga memiliki kualitas data yang lebih baik karena teknik clustering DBSCAN memiliki kemampuan untuk memisahkan noise dari data input

dbscan: Fast Density-Based Clustering with R

This article describes the implementation and use of the R package dbscan, which provides complete and fast implementations of the popular density-based clustering algorithm DBSCAN and the augmented ordering algorithm OPTICS. Package dbscan uses advanced open-source spatial indexing data structures implemented in C++ to speed up computation. An important advantage of this implementation is that it is up-to-date with several improvements that have been added since the original algorithms were publications (e.g., artifact corrections and dendrogram extraction methods for OPTICS). We provide a consistent presentation of the DBSCAN and OPTICS algorithms, and compare dbscan's implementation with other popular libraries such as the R package fpc, ELKI, WEKA, PyClustering, SciKit-Learn, and SPMF in terms of available features and using an experimental comparison

Implementasi Algoritma Penentuan Parameter Densitas Pada Metode Dbscan Untuk Pengelompokan Data

DBSCAN adalah salah satu metode klastering dengan konsep kerapatan data. Ketika data memiliki densitas beragam maka hasil pengklasteran DBSCAN tidak maksimal. Hal ini disebabkan nilai parameter densitas bersifat global untuk seluruh data. Implementasi tugas akhir ini menyelesaikan permasalahan tersebut menggunakan modifikasi DBSCAN sehingga nilai parameter densitas akan berbeda untuk setiap klaster. Nilai parameter densitas didapatkan dari hasil knearest neighbor beberapa data agar data terambil bukanlah noise atau outlier. Uji coba dilakukan dengan membandingkan hasil metode DBSCAN dengan DBSCAN yang telah dimodifikasi. Indikator keberhasilan uji coba menggunakan uji validitas klaster Indeks Dunn. Hasil uji coba validitas indeks menunjukkan bahwa DBSCAN modifikasi memiliki hasil klaster yang kurang baik dibandingkan hasil DBSCAN dengan nilai rata-rata Indeks Dunn 0.12 dan 0.146. Uji coba juga dilakukan dengan melihat label data dari kelas yang dihasilkan dengan kelas groundtruth. Pada uji coba ini DBSCAN modifikasi dapat mengidentifikasi hasil klaster yang lebih mirip dengan data aslinya dibanding dengan hasil DBSCAN tanpa modifikasi. =============================================================================================== DBSCAN is a clustering algorithm based on density concept. DBSCAN clustering results could not be optimal if data have a variation of densities level because density parameter values applied for the entire data clusters. Our implementation resolved the problems using a modified DBSCAN so that the density parameter values will be different for each cluster. Density parameter values are obtained from the k-nearest neighbor implementation in some data to recognize data outliers. Our experiments were comparing clustering results of DBSCAN and modified DBSCAN algorithms. We used Dunn Index as cluster validity measures. The results showed that Dunn Index values of modified DBSCAN were not better compared to the results of standard DBSCAN with Dunn Index of 0.12 and 0.146 respectively. However our experiments also compared data label of clustering results with label in groundtruth dataset. Labelling experiments showed that clustering results of modified DBSCAN algorithms had more similar label with ground-truth dataset

Modelling the head and neck region for microwave imaging of cervical lymph nodes

Tese de mestrado integrado, Engenharia Biomédica e Biofísica (Radiações em Diagnóstico e Terapia), Universidade de Lisboa, Faculdade de Ciências, 2020O termo “cancro da cabeça e pescoço” refere-se a um qualquer tipo de cancro com início nas células epiteliais das cavidades oral e nasal, seios perinasais, glândulas salivares, faringe e laringe. Estes tumores malignos apresentaram, em 2018, uma incidência mundial de cerca de 887.659 novos casos e taxa de mortalidade superior a 51%. Aproximadamente 80% dos novos casos diagnosticados nesse ano revelaram a proliferação de células cancerígenas dos tumores para outras regiões do corpo através dos vasos sanguíneos e linfáticos das redondezas. De forma a determinar o estado de desenvolvimento do cancro e as terapias a serem seguidas, é fundamental a avaliação dos primeiros gânglios linfáticos que recebem a drenagem do tumor primário – os gânglios sentinela – e que, por isso, apresentam maior probabilidade de se tornarem os primeiros alvos das células tumorais. Gânglios sentinela saudáveis implicam uma menor probabilidade de surgirem metástases, isto é, novos focos tumorais decorrentes da disseminação do cancro para outros órgãos. O procedimento standard que permite o diagnóstico dos gânglios linfáticos cervicais, gânglios que se encontram na região da cabeça e pescoço, e o estadiamento do cancro consiste na remoção cirúrgica destes gânglios e subsequente histopatologia. Para além de ser um procedimento invasivo, a excisão cirúrgica dos gânglios linfáticos representa perigos tanto para a saúde mental e física dos pacientes, como para a sua qualidade de vida. Dores, aparência física deformada (devido a cicatrizes), perda da fala ou da capacidade de deglutição são algumas das repercussões que poderão advir da remoção de gânglios linfáticos da região da cabeça e pescoço. Adicionalmente, o risco de infeção e linfedema – acumulação de linfa nos tecidos intersticiais – aumenta significativamente com a remoção de uma grande quantidade de gânglios linfáticos saudáveis. Também os encargos para os sistemas de saúde são elevados devido à necessidade de monitorização destes pacientes e subsequentes terapias e cuidados associados à morbilidade, como é o caso da drenagem linfática manual e da fisioterapia. O desenvolvimento de novas tecnologias de imagem da cabeça e pescoço requer o uso de modelos realistas que simulem o comportamento e propriedades dos tecidos biológicos. A imagem médica por micro-ondas é uma técnica promissora e não invasiva que utiliza radiação não ionizante, isto é, sinais com frequências na gama das micro-ondas cujo comportamento depende do contraste dielétrico entre os diferentes tecidos atravessados, pelo que é possível identificar regiões ou estruturas de interesse e, consequentemente, complementar o diagnóstico. No entanto, devido às suas características, este tipo de modalidade apenas poderá ser utilizado para a avaliação de regiões anatómicas pouco profundas. Estudos indicam que os gânglios linfáticos com células tumorais possuem propriedades dielétricas distintas dos gânglios linfáticos saudáveis. Por esta razão e juntamente pelo facto da sua localização pouco profunda, consideramos que os gânglios linfáticos da região da cabeça e pescoço constituem um excelente candidato para a utilização de imagem médica por radar na frequência das micro-ondas como ferramenta de diagnóstico. Até à data, não foram efetuados estudos de desenvolvimento de modelos da região da cabeça e pescoço focados em representar realisticamente os gânglios linfáticos cervicais. Por este motivo, este projeto consistiu no desenvolvimento de dois geradores de fantomas tridimensionais da região da cabeça e pescoço – um gerador de fantomas numéricos simples (gerador I) e um gerador de fantomas numéricos mais complexos e anatomicamente realistas, que foi derivado de imagens de ressonância magnética e que inclui as propriedades dielétricas realistas dos tecidos biológicos (gerador II). Ambos os geradores permitem obter fantomas com diferentes níveis de complexidade e assim acompanhar diferentes fases no processo de desenvolvimento de equipamentos médicos de imagiologia por micro-ondas. Todos os fantomas gerados, e principalmente os fantomas anatomicamente realistas, poderão ser mais tarde impressos a três dimensões. O processo de construção do gerador I compreendeu a modelação da região da cabeça e pescoço em concordância com a anatomia humana e distribuição dos principais tecidos, e a criação de uma interface para a personalização dos modelos (por exemplo, a inclusão ou remoção de alguns tecidos é dependente do propósito para o qual cada modelo é gerado). O estudo minucioso desta região levou à inclusão de tecidos ósseos, musculares e adiposos, pele e gânglios linfáticos nos modelos. Apesar destes fantomas serem bastante simples, são essenciais para o início do processo de desenvolvimento de dispositivos de imagem médica por micro-ondas dedicados ao diagnóstico dos gânglios linfáticos cervicais. O processo de construção do gerador II foi fracionado em 3 grandes etapas devido ao seu elevado grau de complexidade. A primeira etapa consistiu na criação de uma pipeline que permitiu o processamento das imagens de ressonância magnética. Esta pipeline incluiu: a normalização dos dados, a subtração do background com recurso a máscaras binárias manualmente construídas, o tratamento das imagens através do uso de filtros lineares (como por exemplo, filtros passa-baixo ideal, Gaussiano e Butterworth) e não-lineares (por exemplo, o filtro mediana), e o uso de algoritmos não supervisionados de machine learning para a segmentação dos vários tecidos biológicos presentes na região cervical, tais como o K-means, Agglomerative Hierarchical Clustering, DBSCAN e BIRCH. Visto que cada algoritmo não supervisionado de machine learning anteriormente referido requer diferentes hiperparâmetros, é necessário proceder a um estudo pormenorizado que permita a compreensão do modo de funcionamento de cada algoritmo individualmente e a sua interação / performance com o tipo de dados tratados neste projeto (isto é, dados de exames de ressonâncias magnéticas) com vista a escolher empiricamente o leque de valores de cada hiperparâmetro que deve ser considerado, e ainda as combinações que devem ser testadas. Após esta fase, segue-se a avaliação da combinação de hiperparâmetros que resulta na melhor segmentação das estruturas anatómicas. Para esta avaliação são consideradas duas metodologias que foram combinadas: a utilização de métricas que permitam avaliar a qualidade do clustering (como por exemplo, o Silhoeutte Coefficient, o índice de Davies-Bouldin e o índice de Calinski-Harabasz) e ainda a inspeção visual. A segunda etapa foi dedicada à introdução manual de algumas estruturas, como a pele e os gânglios linfáticos, que não foram segmentadas pelos algoritmos de machine learning devido à sua fina espessura e pequena dimensão, respetivamente. Finalmente, a última etapa consistiu na atribuição das propriedades dielétricas, para uma frequência pré-definida, aos tecidos biológicos através do Modelo de Cole-Cole de quatro pólos. Tal como no gerador I, foi criada uma interface que permitiu ao utilizador decidir que características pretende incluir no fantoma, tais como: os tecidos a incluir (tecido adiposo, tecido muscular, pele e / ou gânglios linfáticos), relativamente aos gânglios linfáticos o utilizador poderá ainda determinar o seu número, dimensões, localização em níveis e estado clínico (saudável ou metastizado) e finalmente, o valor de frequência para o qual pretende obter as propriedades dielétricas (permitividade relativa e condutividade) de cada tecido biológico. Este projeto resultou no desenvolvimento de um gerador de modelos realistas da região da cabeça e pescoço com foco nos gânglios linfáticos cervicais, que permite a inserção de tecidos biológicos, tais como o tecidos muscular e adiposo, pele e gânglios linfáticos e aos quais atribui as propriedades dielétricas para uma determinada frequência na gama de micro-ondas. Estes modelos computacionais resultantes do gerador II, e que poderão ser mais tarde impressos em 3D, podem vir a ter grande impacto no processo de desenvolvimento de dispositivos médicos de imagem por micro-ondas que visam diagnosticar gânglios linfáticos cervicais, e consequentemente, contribuir para um processo não invasivo de estadiamento do cancro da cabeça e pescoço.Head and neck cancer is a broad term referring to any epithelial malignancies arising in the paranasal sinuses, nasal and oral cavities, salivary glands, pharynx, and larynx. In 2018, approximately 80% of the newly diagnosed head and neck cancer cases resulted in tumour cells spreading to neighbouring lymph and blood vessels. In order to determine cancer staging and decide which follow-up exams and therapy to follow, physicians excise and assess the Lymph Nodes (LNs) closest to the primary site of the head and neck tumour – the sentinel nodes – which are the ones with highest probability of being targeted by cancer cells. The standard procedure to diagnose the Cervical Lymph Nodes (CLNs), i.e. lymph nodes within the head and neck region, and determine the cancer staging frequently involves their surgical removal and subsequent histopathology. Besides being invasive, the removal of the lymph nodes also has negative impact on patients’ quality of life, it can be health threatening, and it is costly to healthcare systems due to the patients’ needs for follow-up treatments/cares. Anatomically realistic phantoms are required to develop novel technologies tailored to image head and neck regions. Medical MicroWave Imaging (MWI) is a promising non-invasive approach which uses non-ionizing radiation to screen shallow body regions, therefore cervical lymph nodes are excellent candidates to this imaging modality. In this project, a three-dimensional (3D) numerical phantom generator (generator I) and a Magnetic Resonance Imaging (MRI)-derived anthropomorphic phantom generator (generator II) of the head and neck region were developed to create phantoms with different levels of complexity and realism, which can be later 3D printed to test medical MWI devices. The process of designing the numerical phantom generator included the modelling of the head and neck regions according to their anatomy and the distribution of their main tissues, and the creation of an interface which allowed the users to personalise the model (e.g. include or remove certain tissues, depending on the purpose of each generated model). To build the anthropomorphic phantom generator, the modelling process included the creation of a pipeline of data processing steps to be applied to MRIs of the head and neck, followed by the development of algorithms to introduce additional tissues to the models, such as skin and lymph nodes, and finally, the assignment of the dielectric properties to the biological tissues. Similarly, this generator allowed users to decide the features they wish to include in the phantoms. This project resulted in the creation of a generator of 3D anatomically realistic head and neck phantoms which allows the inclusion of biological tissues such as skin, muscle tissue, adipose tissue, and LNs, and assigns state-of-the-art dielectric properties to the tissues. These phantoms may have a great impact in the development process of MWI devices aimed at screening and diagnosing CLNs, and consequently, contribute to a non-invasive staging of the head and neck cancer

Density-based algorithms for active and anytime clustering

Data intensive applications like biology, medicine, and neuroscience require effective and efficient data mining technologies. Advanced data acquisition methods produce a constantly increasing volume and complexity. As a consequence, the need of new data mining technologies to deal with complex data has emerged during the last decades. In this thesis, we focus on the data mining task of clustering in which objects are separated in different groups (clusters) such that objects inside a cluster are more similar than objects in different clusters. Particularly, we consider density-based clustering algorithms and their applications in biomedicine. The core idea of the density-based clustering algorithm DBSCAN is that each object within a cluster must have a certain number of other objects inside its neighborhood. Compared with other clustering algorithms, DBSCAN has many attractive benefits, e.g., it can detect clusters with arbitrary shape and is robust to outliers, etc. Thus, DBSCAN has attracted a lot of research interest during the last decades with many extensions and applications. In the first part of this thesis, we aim at developing new algorithms based on the DBSCAN paradigm to deal with the new challenges of complex data, particularly expensive distance measures and incomplete availability of the distance matrix. Like many other clustering algorithms, DBSCAN suffers from poor performance when facing expensive distance measures for complex data. To tackle this problem, we propose a new algorithm based on the DBSCAN paradigm, called Anytime Density-based Clustering (A-DBSCAN), that works in an anytime scheme: in contrast to the original batch scheme of DBSCAN, the algorithm A-DBSCAN first produces a quick approximation of the clustering result and then continuously refines the result during the further run. Experts can interrupt the algorithm, examine the results, and choose between (1) stopping the algorithm at any time whenever they are satisfied with the result to save runtime and (2) continuing the algorithm to achieve better results. Such kind of anytime scheme has been proven in the literature as a very useful technique when dealing with time consuming problems. We also introduced an extended version of A-DBSCAN called A-DBSCAN-XS which is more efficient and effective than A-DBSCAN when dealing with expensive distance measures. Since DBSCAN relies on the cardinality of the neighborhood of objects, it requires the full distance matrix to perform. For complex data, these distances are usually expensive, time consuming or even impossible to acquire due to high cost, high time complexity, noisy and missing data, etc. Motivated by these potential difficulties of acquiring the distances among objects, we propose another approach for DBSCAN, called Active Density-based Clustering (Act-DBSCAN). Given a budget limitation B, Act-DBSCAN is only allowed to use up to B pairwise distances ideally to produce the same result as if it has the entire distance matrix at hand. The general idea of Act-DBSCAN is that it actively selects the most promising pairs of objects to calculate the distances between them and tries to approximate as much as possible the desired clustering result with each distance calculation. This scheme provides an efficient way to reduce the total cost needed to perform the clustering. Thus it limits the potential weakness of DBSCAN when dealing with the distance sparseness problem of complex data. As a fundamental data clustering algorithm, density-based clustering has many applications in diverse fields. In the second part of this thesis, we focus on an application of density-based clustering in neuroscience: the segmentation of the white matter fiber tracts in human brain acquired from Diffusion Tensor Imaging (DTI). We propose a model to evaluate the similarity between two fibers as a combination of structural similarity and connectivity-related similarity of fiber tracts. Various distance measure techniques from fields like time-sequence mining are adapted to calculate the structural similarity of fibers. Density-based clustering is used as the segmentation algorithm. We show how A-DBSCAN and A-DBSCAN-XS are used as novel solutions for the segmentation of massive fiber datasets and provide unique features to assist experts during the fiber segmentation process.Datenintensive Anwendungen wie Biologie, Medizin und Neurowissenschaften erfordern effektive und effiziente Data-Mining-Technologien. Erweiterte Methoden der Datenerfassung erzeugen stetig wachsende Datenmengen und Komplexit\"at. In den letzten Jahrzehnten hat sich daher ein Bedarf an neuen Data-Mining-Technologien f\"ur komplexe Daten ergeben. In dieser Arbeit konzentrieren wir uns auf die Data-Mining-Aufgabe des Clusterings, in der Objekte in verschiedenen Gruppen (Cluster) getrennt werden, so dass Objekte in einem Cluster untereinander viel \"ahnlicher sind als Objekte in verschiedenen Clustern. Insbesondere betrachten wir dichtebasierte Clustering-Algorithmen und ihre Anwendungen in der Biomedizin. Der Kerngedanke des dichtebasierten Clustering-Algorithmus DBSCAN ist, dass jedes Objekt in einem Cluster eine bestimmte Anzahl von anderen Objekten in seiner Nachbarschaft haben muss. Im Vergleich mit anderen Clustering-Algorithmen hat DBSCAN viele attraktive Vorteile, zum Beispiel kann es Cluster mit beliebiger Form erkennen und ist robust gegen\"uber Ausrei{\ss}ern. So hat DBSCAN in den letzten Jahrzehnten gro{\ss}es Forschungsinteresse mit vielen Erweiterungen und Anwendungen auf sich gezogen. Im ersten Teil dieser Arbeit wollen wir auf die Entwicklung neuer Algorithmen eingehen, die auf dem DBSCAN Paradigma basieren, um mit den neuen Herausforderungen der komplexen Daten, insbesondere teurer Abstandsma{\ss}e und unvollst\"andiger Verf\"ugbarkeit der Distanzmatrix umzugehen. Wie viele andere Clustering-Algorithmen leidet DBSCAN an schlechter Per- formanz, wenn es teuren Abstandsma{\ss}en f\"ur komplexe Daten gegen\"uber steht. Um dieses Problem zu l\"osen, schlagen wir einen neuen Algorithmus vor, der auf dem DBSCAN Paradigma basiert, genannt Anytime Density-based Clustering (A-DBSCAN), der mit einem Anytime Schema funktioniert. Im Gegensatz zu dem urspr\"unglichen Schema DBSCAN, erzeugt der Algorithmus A-DBSCAN zuerst eine schnelle Ann\"aherung des Clusterings-Ergebnisses und verfeinert dann kontinuierlich das Ergebnis im weiteren Verlauf. Experten k\"onnen den Algorithmus unterbrechen, die Ergebnisse pr\"ufen und w\"ahlen zwischen (1) Anhalten des Algorithmus zu jeder Zeit, wann immer sie mit dem Ergebnis zufrieden sind, um Laufzeit sparen und (2) Fortsetzen des Algorithmus, um bessere Ergebnisse zu erzielen. Eine solche Art eines "Anytime Schemas" ist in der Literatur als eine sehr n\"utzliche Technik erprobt, wenn zeitaufwendige Problemen anfallen. Wir stellen auch eine erweiterte Version von A-DBSCAN als A-DBSCAN-XS vor, die effizienter und effektiver als A-DBSCAN beim Umgang mit teuren Abstandsma{\ss}en ist. Da DBSCAN auf der Kardinalit\"at der Nachbarschaftsobjekte beruht, ist es notwendig, die volle Distanzmatrix auszurechen. F\"ur komplexe Daten sind diese Distanzen in der Regel teuer, zeitaufwendig oder sogar unm\"oglich zu errechnen, aufgrund der hohen Kosten, einer hohen Zeitkomplexit\"at oder verrauschten und fehlende Daten. Motiviert durch diese m\"oglichen Schwierigkeiten der Berechnung von Entfernungen zwischen Objekten, schlagen wir einen anderen Ansatz f\"ur DBSCAN vor, namentlich Active Density-based Clustering (Act-DBSCAN). Bei einer Budgetbegrenzung B, darf Act-DBSCAN nur bis zu B ideale paarweise Distanzen verwenden, um das gleiche Ergebnis zu produzieren, wie wenn es die gesamte Distanzmatrix zur Hand h\"atte. Die allgemeine Idee von Act-DBSCAN ist, dass es aktiv die erfolgversprechendsten Paare von Objekten w\"ahlt, um die Abst\"ande zwischen ihnen zu berechnen, und versucht, sich so viel wie m\"oglich dem gew\"unschten Clustering mit jeder Abstandsberechnung zu n\"ahern. Dieses Schema bietet eine effiziente M\"oglichkeit, die Gesamtkosten der Durchf\"uhrung des Clusterings zu reduzieren. So schr\"ankt sie die potenzielle Schw\"ache des DBSCAN beim Umgang mit dem Distance Sparseness Problem von komplexen Daten ein. Als fundamentaler Clustering-Algorithmus, hat dichte-basiertes Clustering viele Anwendungen in den unterschiedlichen Bereichen. Im zweiten Teil dieser Arbeit konzentrieren wir uns auf eine Anwendung des dichte-basierten Clusterings in den Neurowissenschaften: Die Segmentierung der wei{\ss}en Substanz bei Faserbahnen im menschlichen Gehirn, die vom Diffusion Tensor Imaging (DTI) erfasst werden. Wir schlagen ein Modell vor, um die \"Ahnlichkeit zwischen zwei Fasern als einer Kombination von struktureller und konnektivit\"atsbezogener \"Ahnlichkeit von Faserbahnen zu beurteilen. Verschiedene Abstandsma{\ss}e aus Bereichen wie dem Time-Sequence Mining werden angepasst, um die strukturelle \"Ahnlichkeit von Fasern zu berechnen. Dichte-basiertes Clustering wird als Segmentierungsalgorithmus verwendet. Wir zeigen, wie A-DBSCAN und A-DBSCAN-XS als neuartige L\"osungen f\"ur die Segmentierung von sehr gro{\ss}en Faserdatens\"atzen verwendet werden, und bieten innovative Funktionen, um Experten w\"ahrend des Fasersegmentierungsprozesses zu unterst\"utzen

Image Processing and Simulation Toolboxes of Microscopy Images of Bacterial Cells

Recent advances in microscopy imaging technology have allowed the characterization of the dynamics of cellular processes at the single-cell and single-molecule level. Particularly in bacterial cell studies, and using the E. coli as a case study, these techniques have been used to detect and track internal cell structures such as the Nucleoid and the Cell Wall and fluorescently tagged molecular aggregates such as FtsZ proteins, Min system proteins, inclusion bodies and all the different types of RNA molecules. These studies have been performed with using multi-modal, multi-process, time-lapse microscopy, producing both morphological and functional images. To facilitate the finding of relationships between cellular processes, from small-scale, such as gene expression, to large-scale, such as cell division, an image processing toolbox was implemented with several automatic and/or manual features such as, cell segmentation and tracking, intra-modal and intra-modal image registration, as well as the detection, counting and characterization of several cellular components. Two segmentation algorithms of cellular component were implemented, the first one based on the Gaussian Distribution and the second based on Thresholding and morphological structuring functions. These algorithms were used to perform the segmentation of Nucleoids and to identify the different stages of FtsZ Ring formation (allied with the use of machine learning algorithms), which allowed to understand how the temperature influences the physical properties of the Nucleoid and correlated those properties with the exclusion of protein aggregates from the center of the cell. Another study used the segmentation algorithms to study how the temperature affects the formation of the FtsZ Ring. The validation of the developed image processing methods and techniques has been based on benchmark databases manually produced and curated by experts. When dealing with thousands of cells and hundreds of images, these manually generated datasets can become the biggest cost in a research project. To expedite these studies in terms of time and lower the cost of the manual labour, an image simulation was implemented to generate realistic artificial images. The proposed image simulation toolbox can generate biologically inspired objects that mimic the spatial and temporal organization of bacterial cells and their processes, such as cell growth and division and cell motility, and cell morphology (shape, size and cluster organization). The image simulation toolbox was shown to be useful in the validation of three cell tracking algorithms: Simple Nearest-Neighbour, Nearest-Neighbour with Morphology and DBSCAN cluster identification algorithm. It was shown that the Simple Nearest-Neighbour still performed with great reliability when simulating objects with small velocities, while the other algorithms performed better for higher velocities and when there were larger clusters present

Particle – particle interactions in dry powder blending:Applying theoretical concepts to real-life particles

Geneesmiddelen zijn bijna altijd mengsels van een of meer actieve stoffen en een aantal hulpstoffen. Heel vaak zijn deze grondstoffen poedervormig. Omdat patiënten zeker moeten zijn van juiste dosering van het geneesmiddel en juiste werking van het product, zoals een tablet of capsule, moeten zeer hoge eisen worden gesteld aan de verdeling van de componenten in het mengsel. Het (droog) mengen van poeders is daarom een kritische processtap. Veel grondstoffen bestaan uit cohesieve deeltjes. Dergelijke deeltjes hebben de neiging om aan elkaar te plakken, te agglomereren. Hierdoor ontstaan grote, vaak sterkte, klonten. Aanwezigheid van deze klonten in het eindproduct kan leiden tot verschillende gezondheidsrisico’s als gevolg van overdosering van het geneesmiddel. Begrip hoe klonten ontstaan en breken is daarom essentieel om garanties ten aanzien van productkwaliteit te kunnen geven. Dit proefschrift gaat in op deeltjesinteracties tussen deeltjes die een complexe vorm hebben en poogt relaties te leggen met de sterkte van agglomeraten. Adhesiekrachten tussen poederdeeltjes werden gemeten met de centrifuge methode en met atomic force microscopy (AFM). De structuren van agglomeraten werden bestudeerd met 3D Röntgen microtomografie (XMT). Een numerieke simulatie uitgevoerd met Discrete Element Method (DEM) werd gebruikt om deeltjesgrootteverkleining en uiteenvallen van agglomeraten in een mengproces te bestuderen. Dimensieloos Stokes-slijtage getal werd gebruikt om deeltjesgrootteverkleining van agglomeraten te beschrijven. De validiteit van het slijtage model werd geverifieerd met simulatie en experimentele data. Het model geeft advies om selectie van vulstoffen en process-settings te kiezen gedurende ontwikkeling van farmaceutische producten

Evolutionary and Swarm Algorithm Optimized Density- Based Clustering and Classification for Data Analytics

Clustering is one of the most widely used pattern recognition technologies for data analytics. Density-based clustering is a category of clustering methods which can find arbitrary shaped clusters. A well-known density-based clustering algorithm is Density- Based Spatial Clustering of Applications with Noise (DBSCAN). DBSCAN has three drawbacks: firstly, the parameters for DBSCAN are hard to set; secondly, the number of clusters cannot be controlled by the users; and thirdly, DBSCAN cannot directly be used as a classifier. With addressing the drawbacks of DBSCAN, a novel framework, Evolutionary and Swarm Algorithm optimised Density-based Clustering and Classification (ESA-DCC), is proposed. Evolutionary and Swarm Algorithm (ESA), has been applied in various different research fields regarding optimisation problems, including data analytics. Numerous categories of ESAs have been proposed, such as, Genetic Algorithms (GAs), Particle Swarm Optimization (PSO), Differential Evaluation (DE) and Artificial Bee Colony (ABC). In this thesis, ESA is used to search the best parameters of density-based clustering and classification in the ESA-DCC framework to address the first drawback of DBSCAN. As method to offset the second drawback, four types of fitness functions are defined to enable users to set the number of clusters as input. A supervised fitness function is defined to use the ESA-DCC as a classifier to address the third drawback. Four ESA- DCC methods, GA-DCC, PSO-DCC, DE-DCC and ABC-DCC, are developed. The performance of the ESA-DCC methods is compared with K-means and DBSCAN using ten datasets. The experimental results indicate that the proposed ESA-DCC methods can find the optimised parameters in both supervised and unsupervised contexts. The proposed methods are applied in a product recommender system and image segmentation cases

Mining biomedical images with density-based clustering

Density-based clustering algorithms have recently gained popularity in the data mining field due to their ability to discover arbitrary shaped clusters while preserving spatial proximity of data points. In this work we adapt a density-based clustering algorithm, DBSCAN, to a new problem domain: Identification of homogenous color regions in biomedical images. Examples of specific problems of this nature include landscape segmentation of satellite imagery, object detection and, in our case, identification of significant color regions in images of skin lesions (tumors). Automated outer and inner boundary segmentation is a key step in segmentation of structures such as skin lesions, tumors of breast, bone, and brain. This step is important because the accuracy of the subsequent steps (extraction of various features, post-processing) crucially depends on the accuracy of this very first step. In this paper, we present an unsupervised approach to segmentation of pigmented skin lesion images based on DBSCAN clustering algorithm. The color regions identified by the algorithm are compared to those identified by the human subjects and the Kappa coefficient, a statistical indicator of computerhuman agreement, is found to be significant. 1