Reporting guidelines, review of methodological standards, and challenges toward harmonization in bone marrow adiposity research. Report of the Methodologies Working Group of the International Bone Marrow Adiposity Society

The interest in bone marrow adiposity (BMA) has increased over the last decade due to its association with, and potential role, in a range of diseases (osteoporosis, diabetes, anorexia, cancer) as well as treatments (corticosteroid, radiation, chemotherapy, thiazolidinediones). However, to advance the field of BMA research, standardization of methods is desirable to increase comparability of study outcomes and foster collaboration. Therefore, at the 2017 annual BMA meeting, the International Bone Marrow Adiposity Society (BMAS) founded a working group to evaluate methodologies in BMA research. All BMAS members could volunteer to participate. The working group members, who are all active preclinical or clinical BMA researchers, searched the literature for articles investigating BMA and discussed the results during personal and telephone conferences. According to the consensus opinion, both based on the review of the literature and on expert opinion, we describe existing methodologies and discuss the challenges and future directions for (1) histomorphometry of bone marrow adipocytes, (2

Deep weakly-supervised learning methods for classification and localization in histology images: a survey

Using state-of-the-art deep learning models for cancer diagnosis presents several challenges related to the nature and availability of labeled histology images. In particular, cancer grading and localization in these images normally relies on both image- and pixel-level labels, the latter requiring a costly annotation process. In this survey, deep weakly-supervised learning (WSL) models are investigated to identify and locate diseases in histology images, without the need for pixel-level annotations. Given training data with global image-level labels, these models allow to simultaneously classify histology images and yield pixel-wise localization scores, thereby identifying the corresponding regions of interest (ROI). Since relevant WSL models have mainly been investigated within the computer vision community, and validated on natural scene images, we assess the extent to which they apply to histology images which have challenging properties, e.g. very large size, similarity between foreground/background, highly unstructured regions, stain heterogeneity, and noisy/ambiguous labels. The most relevant models for deep WSL are compared experimentally in terms of accuracy (classification and pixel-wise localization) on several public benchmark histology datasets for breast and colon cancer -- BACH ICIAR 2018, BreaKHis, CAMELYON16, and GlaS. Furthermore, for large-scale evaluation of WSL models on histology images, we propose a protocol to construct WSL datasets from Whole Slide Imaging. Results indicate that several deep learning models can provide a high level of classification accuracy, although accurate pixel-wise localization of cancer regions remains an issue for such images. Code is publicly available.Comment: 35 pages, 18 figure

Tomografia estendida : do básico até o mapeamento de cérebro de camundongos

Orientador: Mateus Borba CardosoTese (doutorado) - Universidade Estadual de Campinas, Instituto de Física Gleb WataghinResumo: Esta tese apresentará uma introdução a imagens de raios-x e como adquirir e processar imagens usando linhas de luz síncrotron. Apresentará os desafios matemáticos e técnicos para reconstruir amostras em três dimensões usando a reconstrução de Tomografia Computadorizada, uma técnica conhecida como CT. Esta técnica tem seu campo de visão limitado ao tamanho da câmera e ao tamanho da iluminação. Uma técnica para ampliar esse campo de visão vai ser apresentada e os desafios técnicos envolvidos para que isso aconteça. Um \textit{pipeline} é proposto e todos os algoritmos necessários foram empacotados em um pacote python chamado Tomosaic. A abordagem baseia-se em adquirir tomogramas parciais em posiçoes pré definidas e depois mesclar os dados em um novo conjunto de dados. Duas maneiras possíveis são apresentadas para essa mescla, uma no domínio das projeções e uma no domínio dos sinogramas. Experimentos iniciais serão então usadas para mostrar que o método proposto funciona com computadores normais. A técnica será aplicada mais tarde para pesquisar a anatomia de cérebros de camundongo completos. Um estudo será apresentado de como obter informação em diferentes escalas do cérebro completo do rato utilizando raios-xAbstract: This thesis will present an introduction to x-ray images and how to acquire and thread images using synchrotron beamlines. It will present the mathematical and technical challenges to reconstruct samples in three dimensions using Computed Tomography reconstruction, a technique known as CT. This technique has a field of view bounded to the camera size and the illumination size. A technique to extended this field of view is going to be presented and the technical challenges involved in order for that to happen will be described. A pipeline is proposed and all the necessary algorithms are contained into a python packaged called Tomosaic. The approach relies on acquired partial tomogram data in a defined grid and later merging the data into a new dataset. Two possible ways are presented in order to that: in the projection domain, and in the sinogram domain. Initial experiments will then be used to show that the pipeline works with normal computers. The technique will be later applied to survey the whole anatomy of whole mouse brains. A study will be shown of how to get the complete range of scales of the mouse brain using x-ray tomography at different resolutionsDoutoradoFísicaDoutor em Ciências163304/2013-01247445/2013, 1456912/2014CNPQCAPE

Differently stained whole slide image registration technique with landmark validation

Abstract. One of the most significant features in digital pathology is to compare and fuse successive differently stained tissue sections, also called slides, visually. Doing so, aligning different images to a common frame, ground truth, is required. Current sample scanning tools enable to create images full of informative layers of digitalized tissues, stored with a high resolution into whole slide images. However, there are a limited amount of automatic alignment tools handling large images precisely in acceptable processing time. The idea of this study is to propose a deep learning solution for histopathology image registration. The main focus is on the understanding of landmark validation and the impact of stain augmentation on differently stained histopathology images. Also, the developed registration method is compared with the state-of-the-art algorithms which utilize whole slide images in the field of digital pathology. There are previous studies about histopathology, digital pathology, whole slide imaging and image registration, color staining, data augmentation, and deep learning that are referenced in this study. The goal is to develop a learning-based registration framework specifically for high-resolution histopathology image registration. Different whole slide tissue sample images are used with a resolution of up to 40x magnification. The images are organized into sets of consecutive, differently dyed sections, and the aim is to register the images based on only the visible tissue and ignore the background. Significant structures in the tissue are marked with landmarks. The quality measurements include, for example, the relative target registration error, structural similarity index metric, visual evaluation, landmark-based evaluation, matching points, and image details. These results are comparable and can be used also in the future research and in development of new tools. Moreover, the results are expected to show how the theory and practice are combined in whole slide image registration challenges. DeepHistReg algorithm will be studied to better understand the development of stain color feature augmentation-based image registration tool of this study. Matlab and Aperio ImageScope are the tools to annotate and validate the image, and Python is used to develop the algorithm of this new registration tool. As cancer is globally a serious disease regardless of age or lifestyle, it is important to find ways to develop the systems experts can use while working with patients’ data. There is still a lot to improve in the field of digital pathology and this study is one step toward it.Eri menetelmin värjättyjen virtuaalinäytelasien rekisteröintitekniikka kiintopisteiden validointia hyödyntäen. Tiivistelmä. Yksi tärkeimmistä digitaalipatologian ominaisuuksista on verrata ja fuusioida peräkkäisiä eri menetelmin värjättyjä kudosleikkeitä toisiinsa visuaalisesti. Tällöin keskenään lähes identtiset kuvat kohdistetaan samaan yhteiseen kehykseen, niin sanottuun pohjatotuuteen. Nykyiset näytteiden skannaustyökalut mahdollistavat sellaisten kuvien luonnin, jotka ovat täynnä kerroksittaista tietoa digitalisoiduista näytteistä, tallennettuna erittäin korkean resoluution virtuaalisiin näytelaseihin. Tällä hetkellä on olemassa kuitenkin vain kourallinen automaattisia työkaluja, jotka kykenevät käsittelemään näin valtavia kuvatiedostoja tarkasti hyväksytyin aikarajoin. Tämän työn tarkoituksena on syväoppimista hyväksikäyttäen löytää ratkaisu histopatologisten kuvien rekisteröintiin. Tärkeimpänä osa-alueena on ymmärtää kiintopisteiden validoinnin periaatteet sekä eri väriaineiden augmentoinnin vaikutus. Lisäksi tässä työssä kehitettyä rekisteröintialgoritmia tullaan vertailemaan muihin kirjallisuudessa esitettyihin algoritmeihin, jotka myös hyödyntävät virtuaalinäytelaseja digitaalipatologian saralla. Kirjallisessa osiossa tullaan siteeraamaan aiempia tutkimuksia muun muassa seuraavista aihealueista: histopatologia, digitaalipatologia, virtuaalinäytelasi, kuvantaminen ja rekisteröinti, näytteen värjäys, data-augmentointi sekä syväoppiminen. Tavoitteena on kehittää oppimispohjainen rekisteröintikehys erityisesti korkearesoluutioisille digitalisoiduille histopatologisille kuville. Erilaisissa näytekuvissa tullaan käyttämään jopa 40-kertaista suurennosta. Kuvat kudoksista on järjestetty eri menetelmin värjättyihin peräkkäisiin kuvasarjoihin ja tämän työn päämääränä on rekisteröidä kuvat pohjautuen ainoastaan kudosten näkyviin osuuksiin, jättäen kuvien tausta huomioimatta. Kudosten merkittävimmät rakenteet on merkattu niin sanotuin kiintopistein. Työn laatumittauksina käytetään arvoja, kuten kohteen suhteellinen rekisteröintivirhe (rTRE), rakenteellisen samankaltaisuuindeksin mittari (SSIM), sekä visuaalista arviointia, kiintopisteisiin pohjautuvaa arviointia, yhteensopivuuskohtia, ja kuvatiedoston yksityiskohtia. Nämä arvot ovat verrattavissa myös tulevissa tutkimuksissa ja samaisia arvoja voidaan käyttää uusia työkaluja kehiteltäessä. DeepHistReg metodi toimii pohjana tässä työssä kehitettävälle näytteen värjäyksen parantamiseen pohjautuvalle rekisteröintityökalulle. Matlab ja Aperio ImageScope ovat ohjelmistoja, joita tullaan hyödyntämään tässä työssä kuvien merkitsemiseen ja validointiin. Ohjelmointikielenä käytetään Pythonia. Syöpä on maailmanlaajuisesti vakava sairaus, joka ei katso ikää eikä elämäntyyliä. Siksi on tärkeää löytää uusia keinoja kehittää työkaluja, joita asiantuntijat voivat hyödyntää jokapäiväisessä työssään potilastietojen käsittelyssä. Digitaalipatologian osa-alueella on vielä paljon innovoitavaa ja tämä työ on yksi askel eteenpäin taistelussa syöpäsairauksia vastaan

Learning Instance Segmentation from Sparse Supervision

Instance segmentation is an important task in many domains of automatic image processing, such as self-driving cars, robotics and microscopy data analysis. Recently, deep learning-based algorithms have brought image segmentation close to human performance. However, most existing models rely on dense groundtruth labels for training, which are expensive, time consuming and often require experienced annotators to perform the labeling. Besides the annotation burden, training complex high-capacity neural networks depends upon non-trivial expertise in the choice and tuning of hyperparameters, making the adoption of these models challenging for researchers in other fields. The aim of this work is twofold. The first is to make the deep learning segmentation methods accessible to non-specialist. The second is to address the dense annotation problem by developing instance segmentation methods trainable with limited groundtruth data. In the first part of this thesis, I bring state-of-the-art instance segmentation methods closer to non-experts by developing PlantSeg: a pipeline for volumetric segmentation of light microscopy images of biological tissues into cells. PlantSeg comes with a large repository of pre-trained models and delivers highly accurate results on a variety of samples and image modalities. We exemplify its usefulness to answer biological questions in several collaborative research projects. In the second part, I tackle the dense annotation bottleneck by introducing SPOCO, an instance segmentation method, which can be trained from just a few annotated objects. It demonstrates strong segmentation performance on challenging natural and biological benchmark datasets at a very reduced manual annotation cost and delivers state-of-the-art results on the CVPPP benchmark. In summary, my contributions enable training of instance segmentation models with limited amounts of labeled data and make these methods more accessible for non-experts, speeding up the process of quantitative data analysis

3D CNN methods in biomedical image segmentation

A definite trend in Biomedical Imaging is the one towards the integration of increasingly complex interpretative layers to the pure data acquisition process. One of the most interesting and looked-forward goals in the field is the automatic segmentation of objects of interest in extensive acquisition data, target that would allow Biomedical Imaging to look beyond its use as a purely assistive tool to become a cornerstone in ambitious large-scale challenges like the extensive quantitative study of the Human Brain. In 2019 Convolutional Neural Networks represent the state of the art in Biomedical Image segmentation and scientific interests from a variety of fields, spacing from automotive to natural resource exploration, converge to their development. While most of the applications of CNNs are focused on single-image segmentation, biomedical image data -being it MRI, CT-scans, Microscopy, etc- often benefits from three-dimensional volumetric expression. This work explores a reformulation of the CNN segmentation problem that is native to the 3D nature of the data, with particular interest to the applications to Fluorescence Microscopy volumetric data produced at the European Laboratories for Nonlinear Spectroscopy in the context of two different large international human brain study projects: the Human Brain Project and the White House BRAIN Initiative

A Framework for the Semantics-aware Modelling of Objects

The evolution of 3D visual content calls for innovative methods for modelling shapes based on their intended usage, function and role in a complex scenario. Even if different attempts have been done in this direction, shape modelling still mainly focuses on geometry. However, 3D models have a structure, given by the arrangement of salient parts, and shape and structure are deeply related to semantics and functionality. Changing geometry without semantic clues may invalidate such functionalities or the meaning of objects or their parts. We approach the problem by considering semantics as the formalised knowledge related to a category of objects; the geometry can vary provided that the semantics is preserved. We represent the semantics and the variable geometry of a class of shapes through the parametric template: an annotated 3D model whose geometry can be deformed provided that some semantic constraints remain satisfied. In this work, we design and develop a framework for the semantics-aware modelling of shapes, offering the user a single application environment where the whole workflow of defining the parametric template and applying semantics-aware deformations can take place. In particular, the system provides tools for the selection and annotation of geometry based on a formalised contextual knowledge; shape analysis methods to derive new knowledge implicitly encoded in the geometry, and possibly enrich the given semantics; a set of constraints that the user can apply to salient parts and a deformation operation that takes into account the semantic constraints and provides an optimal solution. The framework is modular so that new tools can be continuously added. While producing some innovative results in specific areas, the goal of this work is the development of a comprehensive framework combining state of the art techniques and new algorithms, thus enabling the user to conceptualise her/his knowledge and model geometric shapes. The original contributions regard the formalisation of the concept of annotation, with attached properties, and of the relations between significant parts of objects; a new technique for guaranteeing the persistence of annotations after significant changes in shape's resolution; the exploitation of shape descriptors for the extraction of quantitative information and the assessment of shape variability within a class; and the extension of the popular cage-based deformation techniques to include constraints on the allowed displacement of vertices. In this thesis, we report the design and development of the framework as well as results in two application scenarios, namely product design and archaeological reconstruction

Advanced sensing technologies and systems for lung function assessment

Chest X-rays and computed tomography scans are highly accurate lung assessment tools, but their hazardous nature and high cost remain a barrier for many patients. Acoustic imaging is an alternative to lung function assessment that is non-hazardous, less costly, and has a patient-to-equipment approach. In this thesis, the suitability of acoustic imaging for lung health assessment is proven via systematic review and numerical airway modelling. An acoustic lung sound acquisition system, consisting of an optimal denoising filter translated into imaging for continual and reliable lung function assessment, is then developed. To the author’s best knowledge, locating obstructed airways via an acoustic lung model andthe resulting acoustic lung imaging have yet to be investigated in the open literature; hence,a novel acoustic lung spatial model was first developed in this research, which links acousticlung sounds and acoustic images with pathologic changes. About 89% structural similaritybetween an acoustic reference image based on actual lung sound and the developed modelacoustic image based on the computation of airway impedance was achieved. External interference is inevitable in lung sound recordings; thus, an indirect unifying of wavelet-based total variation (WATV) and empirical Wiener denoising filter is proposed to enhance recorded lung sound signals. To the author’s best knowledge, the integration of WATV and Wiener filters has not been investigated for lung sound signals. Selection and analysis of optimal parameters for the denoising filter were performed through a case study. The optimal parameters achieved through simulation studies led to an average 12.69 ± 5.05 dB improvement in signal-to-noise ratio (SNR), and the average SNR was improved by 16.92 ± 8.51 dB in the experimental studies. The hybrid denoising filter significantly enhances the signal quality of the captured lung sounds while preserving the characteristics of a lung sound signal and is less sensitive to the variation of SNR values of the input signal. A robust system was developed based on the established lung spatial model and denoising filter through hardware redesign and signal processing, which outperformed commercial digital stethoscopes regarding SNR and root mean square error by about 8 dB and 0.15, respectively. Regarding sensing sensitivity power spectrum mapping, the developed system sensors’ position is neutral, as opposed to digital stethoscopes, when representing lung signals, with a signal power loss ratio of around 5 dB compared to 10 dB from digital stethoscopes. The developed system obtains better detection by about 10% in the obstructed airway region compared to digital stethoscopes in the experimental studies