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Journal articles

Authors affiliated with CBA are in bold.
  1. Improving the Stochastic Watershed
    Authors: Karl B. Bernander, Kenneth Gustavsson, Bettina Selig, Ida-Maria Sintorn, Cris L. Luengo Hendriks
    Journal: Pattern Recognition Letters, volume 34, number 9, pages 993-1000
    Abstract: The stochastic watershed is an unsupervised segmentation tool recently proposed by Angulo and Jeulin. By repeated application of the seeded watershed with randomly placed markers, a probability density function for object boundaries is created. In a second step, the algorithm then generates a meaningful segmentation of the image using this probability density function. The method performs best when the image contains regions of similar size, since it tends to break up larger regions and merge smaller ones. We propose two simple modifications that greatly improve the properties of the stochastic watershed: (1) add noise to the input image at every iteration, and (2) distribute the markers using a randomly placed grid. The noise strength is a new parameter to be set, but the output of the algorithm is not very sensitive to this value. In return, the output becomes less sensitive to the two parameters of the standard algorithm. The improved algorithm does not break up larger regions, effectively making the algorithm useful for a larger class of segmentation problems.

  2. A Fast and Reliable Approach to Cell Nuclei Segmentation in PAP Stained Cervical Smears
    Authors: Balakrishnan Bujy (1), Vilayil Sujathan (2) Patrik Malm, Rajesh Kumar (1)
    (1) CDAC Thiruvananthapuram, India
    (2) Regional Cancer Centre, Thiruvananthapuram, India
    Journal: CSI Transactions on ICT, Volume 1, number 4, pages 309-315
    Abstract: Fast and reliable segmentation of cervical cell nuclei is one of the crucial steps of an automated screening system that aims early detection of cervical cancer. In this paper, we propose an edge based approach using customized Laplacian of Gaussian (LoG) filter to segment free lying cell nuclei in bright-field microscope images of Papsmear. The LoG is generally employed as a second order edge detector in image processing. The images may have the challenges of inconsistent staining, overlapping and folded cells. Experimenting proposed method over all types of cervical images including sufficient number of high grade lesions of cervical cancer shows that our method performs well for stain varied images containing focused nuclei.

  3. Virtual Surgery "Virtuell Kirurgi"
    Author: Ingrid Carlbom, Mats Karlsson
    Journal: Tandläkartidningen, number 6, pages 12-15
    Abstract: Virtual surgery - a dream? Not at all; in just a few years it might be the reality. The surgeon can already today perform a virtual rehearsal of the real surgery. (in Swedish)

  4. Blind Color Decomposition of Histological Images
    Authors: Milan Gavrilovic, Jimmy Azar, Joakim Lindblad, Carolina Wählby, Ewert Bengtsson, Christer Busch (1), Ingrid Carlbom
    (1) Dept. of Immunology, Genetics and Pathology, Uppsala University
    Journal: IEEE Transactions on Medical Imaging, volume 32, number 6, pages 983-994
    Abstract: Cancer diagnosis is based on visual examination under a microscope of tissue sections from biopsies. But whereas pathologists rely on tissue stains to identify morphological features, automated tissue recognition using color is fraught with problems that stem from image intensity variations due to variations in tissue preparation, variations in spectral signatures of the stained tissue, spectral overlap and spatial aliasing in acquisition, and noise at image acquisition. We present a blind method for color decomposition of histological images. The method decouples intensity from color information and bases the decomposition only on the tissue absorption characteristics of each stain. By modeling the charge-coupled device sensor noise, we improve the method accuracy. We extend current linear decomposition methods to include stained tissues where one spectral signature cannot be separated from all combinations of the other tissues' spectral signatures. We demonstrate both qualitatively and quantitatively that our method results in more accurate decompositions than methods based on non-negative matrix factorization and independent component analysis. The result is one density map for each stained tissue type that classifies portions of pixels into the correct stained tissue allowing accurate identification of morphological features that may be linked to cancer.

  5. Canine Body Composition Quantification Using 3 Tesla Fat Water MRI
    Authors: Aliya Gifford (1), Joel Kullberg (1), Johan Berglund (1), Filip Malmberg, Katie C. Coate (2), Phillip E. Williams (2), Alan D. Cherrington(2), Malcolm J. Avison(2), E. Brian Welch (2)
    (1) Dept. of Radiology, Uppsala University
    (2) Institute of Imaging Science,Vanderbilt University, Nashville, TN, USA
    Journal: Journal of Magnetic Resonance Imaging
    Abstract: Purpose: To test the hypothesis that a whole-body fat-water MRI (FWMRI) protocol acquired at 3 Tesla combined with semi-automated image analysis techniques enables precise volume and mass quantification of adipose, lean, and bone tissue depots that agree with static scale mass and scale mass changes in the context of a longitudinal study of large-breed dogs placed on an obesogenic high-fat, high-fructose diet.

    Materials and methods: Six healthy adult male dogs were scanned twice, at weeks 0 (baseline) and 4, of the dietary regiment. FWMRI-derived volumes of adipose tissue (total, visceral, and subcutaneous), lean tissue, and cortical bone were quantified using a semi-automated approach. Volumes were converted to masses using published tissue densities.

    Results: FWMRI-derived total mass corresponds with scale mass with a concordance correlation coefficient of 0.931 (95% confidence interval ), and slope and intercept values of 1.12 and -2.23 kg, respectively. Visceral, subcutaneous and total adipose tissue masses increased significantly from weeks 0 to 4, while neither cortical bone nor lean tissue masses changed significantly. This is evidenced by a mean percent change of 70.2% for visceral, 67.0% for subcutaneous, and 67.1% for total adipose tissue.

    Conclusion: FWMRI can precisely quantify and map body composition with respect to adipose, lean, and bone tissue depots. The described approach provides a valuable tool to examine the role of distinct tissue depots in an established animal model of human metabolic disease."

  6. Optimal RANSAC - Towards a Repeatable Algorithm for Finding the Optimal Set
    Authors: Anders Hast, Johan Nysjö
    Journal: Journal of WSCG, volume 21, number 1, pages 21-30
    Abstract: A novel idea on how to make RANSAC repeatable is presented, which will find the optimal set in nearly every run for certain types of applications. The proposed algorithm can be used for such transformations that can be constructed by more than the minimal points required. We give examples on matching of aerial images using the Direct Linear Transformation, which requires at least four points. Moreover, we give examples on how the algorithm can be used for finding a plane in 3D using three points or more. Due to its random nature, standard RANSAC is not always able to find the optimal set even for moderately contaminated sets and it usually performs badly when the number of inliers is less than 50%. However, our algorithm is capable of finding the optimal set for heavily contaminated sets, even for an inlier ratio under 5%. The proposed algorithm is based on several known methods, which we modify in a unique way and together they produce a result that is quite different from what each method can produce on its own.
  7. Automated Classification of Immunostaining Patterns in Breast Tissue from the Human Protein Atlas
    Authors: Swamidoss Issac Niwas (1), Andreas Kårsnäs (2), Virginie Uhlmann (3,4), P. Palanisamy (1), Caroline Kampf (4), Martin Simonsson (5), Carolina Wählby (3,5), Robin Strand
    (1) Dept. of Electronics and Communication Engineering (ECE), National Institute of Technology (NIT), Tiruchirappalli, India
    (2) Visiopharm A/S, Hørsholm, Denmark
    (3) Imaging Platform, Broad Institute of Harvard and MIT, Cambridge, Massachusetts MA, USA
    (4) Biomedical Imaging Group, École Polytechnique Fédérale de Lausanne (EPFL), Switzerland
    (5) Science for Life Laboratory, SciLifeLab, UU
    (6) Dept. Immunology, Genetics and Pathology, UU
    Journal: Journal of Pathology Informatics, volume 4, number 14
    Abstract: Background: The Human Protein Atlas (HPA) is an effort to map the location of all human proteins ( It contains a large number of histological images of sections from human tissue. Tissue micro arrays (TMA) are imaged by a slide scanning microscope, and each image represents a thin slice of a tissue core with a dark brown antibody specific stain and a blue counter stain. When generating antibodies for protein profiling of the human proteome, an important step in the quality control is to compare staining patterns of different antibodies directed towards the same protein. This comparison is an ultimate control that the antibody recognizes the right protein. In this paper, we propose and evaluate different approaches for classifying sub-cellular antibody staining patterns in breast tissue samples.
    Materials and Methods: The proposed methods include the computation of various features including gray level co-occurrence matrix (GLCM) features, complex wavelet co-occurrence matrix (CWCM) features, and weighted neighbor distance using compound hierarchy of algorithms representing morphology (WND-CHARM)-inspired features. The extracted features are used into two different multivariate classifiers (support vector machine (SVM) and linear discriminant analysis (LDA) classifier). Before extracting features, we use color deconvolution to separate different tissue components, such as the brownly stained positive regions and the blue cellular regions, in the immuno-stained TMA images of breast tissue.
    Results: We present classification results based on combinations of feature measurements. The proposed complex wavelet features and the WND-CHARM features have accuracy similar to that of a human expert.
    Conclusions: Both human experts and the proposed automated methods have difficulties discriminating between nuclear and cytoplasmic staining patterns. This is to a large extent due to mixed staining of nucleus and cytoplasm. Methods for quantification of staining patterns in histopathology have many applications, ranging from antibody quality control to tumor grading.

  8. Color deconvolution method for breast tissue core biopsy images cell nuclei detection and analysis using multiresolution techniques
    Authors: Swamidoss Issac Niwas (1,2), P. Palanisamy (1), Ewert Bengtsson
    (1) Dept. of Electronics and Communication Engineering (ECE), National Institute of Technology (NIT), Tiruchirappalli, India
    (2) Science for Life Laboratory, SciLifeLab, UU
    Journal: International Journal of Imaging and Robotics, volume 9, number 1, pages 61-72
    Abstract: Breast cancer is the second most common cause of cancer induced death in women in the world. Testing for detection of the cancer involves visual microscopic assessment of breast tissue samples such as core needle biopsies. Analysis on this sample by pathologist is crucial for breast cancer patient. In this paper, a color deconvolution method is used to detect nuclei of core needle biopsy images and then it is investigated after decomposition by means of the curvelet transform. The curvelet statistical features are used for breast cancer diagnosis using the Naive Bayes Classifier (NBC) system. The ability of properly trained Naive Bayes Classifiers correctly classify and recognize patterns which is particularly suitable for use in an expert system assisting the diagnosis of cancer tissue samples.

  9. Analysis of Nuclei Textures of Fine Needle Aspirated Cytology Images for Breast Cancer Diagnosis using Complex Daubechies Wavelets
    Authors: Swamidoss Issac Niwas (1,2), P. Palanisamy(1), K. Sujathan(3), Ewert Bengtsson
    (1) National Institute of Technology (NIT), Tiruchirappalli, India
    (2) Science for Life Laboratory, SciLifeLab, UU
    (3) Regional Cancer Centre, Thiruvanathapuram, India
    Journal: Signal Processing, volume 93, number 10, pages 2828-2837
    Abstract: Breast cancer is the most frequent cause of cancer induced death among women in the world. Diagnosis of this cancer can be done through radiological, surgical, and pathological assessments of breast tissue samples. A common test for detection of this cancer involves visual microscopic inspection of Fine Needle Aspiration Cytology (FNAC) samples of breast tissue. The result of analysis on this sample by a cytopathologist is crucial for the breast cancer patient. For the assessment of malignancy, the chromatin texture patterns of the cell nuclei are essential. Wavelet transforms have been shown to be good tools for extracting information about texture. In this paper, it has been investigated whether complex wavelets can provide better performance than the more common real valued wavelet transform. The features extracted through the wavelets are used as input to a k-nn classifier. The correct classification results are obtained as 93.9% for the complex wavelets and 70.3% for the real wavelets.

  10. Swelling of Cellulose Fibres in Composite Materials : Constraint Effects of the Surrounding Matrix
    Authors: Thomas Joffre (1), Erik L. G. Wernersson, Arttu Miettinen (2), Cris L. Luengo Hendriks, E. Kristofer Gamstedt (1)
    (1) Applied Materials Sciences, UU
    (2) Dept. Physiscs, University of Jyväskylä, Finland
    Journal: Composites Science And Technology, volume 74, pages 52-59
    Abstract: Wood fibres have several highly desirable properties as reinforcement in composite materials for structural applications, e.g. high specific stiffness and strength, renewability and low cost. However, one of the main drawbacks is the swelling of these hydrophilic fibres due to moisture uptake. Since the fibres in the composite are generally embedded in a relatively hydrophobic matrix, the surrounding matrix should restrain the swelling of the fibres. The present study investigates this constraint effect and establishes a micromechanical model to predict the swelling of embedded fibres based on experimentally characterised microstructural parameters and hygroelastic properties of the constituents. The predicted swelling is in concert with direct measurement of various wood-pulp fibre composites by means of three-dimensional X-ray microtomographic images.

  11. In Situ Sequencing for RNA Analysis in Preserved Tissue and Cells
    Authors: Rongqin Ke (1,2), Marco Mignardi (1,2), Alexandra Pacureanu (3), Jessica Svedlund (2), Johan Botling (1), Carolina Wählby (3,4), Mats Nilsson (1,2)
    (1) Dept. Immunology, Genetics and Pathology, UU
    (2) Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University
    (3) Science for Life Laboratory, SciLifeLab, UU
    (4) Imaging Platform, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, MA, USA
    Journal: Nature Methods, volume 10, number 9, pages 857-860
    Abstract: Tissue gene expression profiling is performed on homogenates or on populations of isolated single cells to resolve molecular states of different cell types. In both approaches, histological context is lost. We have developed an in situ sequencing method for parallel targeted analysis of short RNA fragments in morphologically preserved cells and tissue. We demonstrate in situ sequencing of point mutations and multiplexed gene expression profiling in human breast cancer tissue sections.

  12. Shape and Volume of Craniofacial Cavities in Intentional Skull Deformations
    Authors: R. H. Khonsari (1,2), M. Friess (3), Johan Nysjö, G. Odri (4), Filip Malmberg, Ingela Nyström, Elias Messo (5), Jan M. Hirsch (5), E. A. M. Cabanis (6), K. H. Kunzelmann (7), J. M. Salagnac (1), P. Corre (1), A. Ohazama (2), P. T. Sharpe (2), P. Charlier (8), R. Olszewski (9)
    (1) Service de Chirurgie Maxillofaciale et Stomatologie, CHU Hôtel-Dieu, Nantes, France
    (2) Department of Craniofacial Development and Stem Cell Research, Dental Institute, King's College London, UK
    (3) Département Hommes, Natures, Sociétés
    CNRS UMR 7206, Muséum National d'Histoire Naturelle, Musée de l'Homme, Paris, France
    (4) Clinique Chirurgicale Orthopédique et Traumatologique, CHU Hôtel-Dieu, Nantes, France
    (5) Dept. of Surgical Sciences, Oral and Maxillo-facial Surgery, Medical Faculty, UU
    (6) Service de Neuroradiologie, Centre Hospitalier National Ophtalmologique des XV-XX, Paris, France
    (7) Poliklinic für Zahnerhaltung und Parodontologie, Ludwig-Maximilians-Universität, Münich, Germany
    (8) Service d'anatomopathologie, Hôpital Raymond-Poincaré, Garches, France
    (9) Service de Chirurgie Maxillofaciale et Stomatologie, Hôpital Saint-Luc, Université Catholique de Louvain, Bruxelles, Belgium
    Journal: American Journal of Physical Anthropology, volume 151, number 1, pages 110-119
    Abstract: Intentional cranial deformations (ICD) have been observed worldwide but are especially prevalent in preColombian cultures. The purpose of this study was to assess the consequences of ICD on three cranial cavities (intracranial cavity, orbits, and maxillary sinuses) and on cranial vault thickness, in order to screen for morphological changes due to the external constraints exerted by the deformation device. We acquired CT-scans for 39 deformed and 19 control skulls. We studied the thickness of the skull vault using qualitative and quantitative methods. We computed the volumes of the orbits, of the maxillary sinuses, and of the intracranial cavity using haptic-aided semi-automatic segmentation. We finally defined 3D distances and angles within orbits and maxillary sinuses based on 27 anatomical landmarks and measured these features on the 58 skulls. Our results show specific bone thickness patterns in some types of ICD, with localized thinning in regions subjected to increased pressure and thickening in other regions. Our findings confirm that volumes of the cranial cavities are not affected by ICDs but that the shapes of the orbits and of the maxillary sinuses are modified in circumferential deformations. We conclude that ICDs can modify the shape of the cranial cavities and the thickness of their walls but conserve their volumes. These results provide new insights into the morphological effects associated with ICDs and call for similar investigations in subjects with deformational plagiocephalies and craniosynostoses.

  13. Evaluation of Noise Robustness for Local Binary Pattern Descriptors in Texture Classification
    Authors: Gustaf Kylberg, Ida-Maria Sintorn
    Journal: EURASIP Journal on Image and Video Processing, 2013:17, 20 pages
    Abstract: Local binary pattern (LBP) operators have become commonly used texture descriptors in recent years. Several new LBP-based descriptors have been proposed, of which some aim at improving robustness to noise. To do this, the thresholding and encoding schemes used in the descriptors are modified. In this article, the robustness to noise for the eight following LBP-based descriptors are evaluated; improved LBP, median binary patterns (MBP), local ternary patterns (LTP), improved LTP (ILTP), local quinary patterns, robust LBP, and fuzzy LBP (FLBP). To put their performance into perspective they are compared to three well-known reference descriptors; the classic LBP, Gabor filter banks (GF), and standard descriptors derived from gray-level co-occurrence matrices. In addition, a roughly five times faster implementation of the FLBP descriptor is presented, and a new descriptor which we call shift LBP is introduced as an even faster approximation to the FLBP. The texture descriptors are compared and evaluated on six texture datasets; Brodatz, KTH-TIPS2b, Kylberg, Mondial Marmi, UIUC, and a Virus texture dataset. After optimizing all parameters for each dataset the descriptors are evaluated under increasing levels of additive Gaussian white noise. The discriminating power of the texture descriptors is assessed using tenfolded cross-validation of a nearest neighbor classifier. The results show that several of the descriptors perform well at low levels of noise while they all suffer, to different degrees, from higher levels of introduced noise. In our tests, ILTP and FLBP show an overall good performance on several datasets. The GF are often very noise robust compared to the LBP-family under moderate to high levels of noise but not necessarily the best descriptor under low levels of added noise. In our tests, MBP is neither a good texture descriptor nor stable to noise.

  14. Brain Pathology After Mild Traumatic Brain Injury: An Exploratory Study by Repeated Magnetic Resonance Examination
    Authors: Marianne Lannsjö (1,2), Raili Raininko (3), Mariana Bustamante (4), Charlotta von Seth (1), Jörgen Borg (5)
    (1) Dept. Neuroscience, Rehabilitation Medicine, UU
    (2) Centre for Research and Development, County Council of Gävleborg/UU
    (3) Dept. Radiology, UU
    (4) M.Sc. student, CBA
    (5) Department of Clinical Sciences, Rehabilitation Medicine, Karolinska Institute, Danderyd Hospital, Stockholm
    Journal: Journal of Rehabilitation Medicine, volume 45, number 8, pages 721-728
    Abstract: Objective: To explore brain pathology after mild traumatic brain injury by repeated magnetic resonance examination.
    Design: A prospective follow-up study.
    Subjects: Nineteen patients with mild traumatic brain injury presenting with Glasgow Coma Scale (GCS) 14-15.
    Methods: The patients were examined on day 2 or 3 and 3-7 months after the injury. The magnetic resonance protocol comprised conventional T1- and T2-weighted sequences including fluid attenuated inversion recovery (FLAIR), two susceptibility-weighted sequences to reveal haemorrhages, and diffusion-weighted sequences. Computer-aided volume comparison was performed. Clinical outcome was assessed by the Rivermead Post-Concussion Symptoms Questionnaire (RPQ), Hospital Anxiety and Depression Scale (HADS) and Glasgow Outcome Scale Extended (GOSE).
    Results: At follow-up, 7 patients (37%) reported symptoms in RPQ, 5 reported some anxiety and 1 reported mild depression. Fifteen patients reported upper level of good recovery and 4 patients lower level of good recovery (GOSE 8 and 7, respectively). Magnetic resonance pathology was found in 1 patient at the first examination, but 4 patients (21%) showed volume loss at the second examination, at which 3 of them reported symptoms and 1 symptoms, all exhibiting GOSE scores of 8.
    Conclusion: Loss of brain volume, demonstrated by computer-aided magnetic resonance imaging volumetry, may be a feasible marker of brain pathology after mild traumatic brain injury.

  15. Debris Removal in Pap-smear Images
    Authors: Patrik Malm, Byju N. Balakrishnan (1), Vilayil K. Sujathan (2), Rajesh Kumar (1), Ewert Bengtsson
    (1) Centre for Development of Advanced Computing, Thiruvananthapuram, India
    (2) Regional Cancer Centre, Thiruvananthapuram, India
    Journal: Computer Methods and Programs in Biomedicine, volume 111, number 1, pages 128-138
    Abstract: Since its introduction in the 1940s the Pap-smear test has helped reduce the incidence of cervical cancer dramatically in countries where regular screening is standard. The automation of this procedure is an open problem that has been ongoing for over fifty years without reaching satisfactory results. Existing systems are discouragingly expensive and yet they are only able to make a correct distinction between normal and abnormal samples in a fraction of cases. Therefore, they are limited to acting as support for the cytotechnicians as they perform their manual screening. The main reason for the current limitations is that the automated systems struggle to overcome the complexity of the cell structures. Samples are covered in artefacts such as blood cells, overlapping and folded cells, and bacteria, that hamper the segmentation processes and generate large number of suspicious objects. The classifiers designed to differentiate between normal cells and pre-cancerous cells produce unpredictable results when classifying artefacts. In this paper, we propose a sequential classification scheme focused on removing unwanted objects, debris, from an initial segmentation result, intended to be run before the actual normal/abnormal classifier. The method has been evaluated using three separate datasets obtained from cervical samples prepared using both the standard Pap-smear approach as well as the more recent liquid based cytology sample preparation technique. We show success in removing more than 99% of the debris without loosing more than around one percent of the epithelial cells detected by the segmentation process.

  16. A New Algorithm for Computing Riemannian Geodesic Distance in Rectangular 2-D and 3-D Grids
    Authors: Ola Nilsson (1), Martin Reimers (2), Ken Museth (1), Anders Brun
    (1) Dept. Science and Technology, Linköping University
    (2) Dept. Informatics, University of Oslo, Norway
    Journal: International Journal on Artificial Intelligence Tools, volume 22, number 6, 25 pages
    Abstract: We present a novel way to efficiently compute Riemannian geodesic distance over a two- or three-dimensional domain. It is based on a previously presented method for computation of geodesic distances on surface meshes. Our method is adapted for rectangular grids, equipped with a variable anisotropic metric tensor. Processing and visualization of such tensor fields is common in certain applications, for instance structure tensor fields in image analysis and diffusion tensor fields in medical imaging.

    The included benchmark study shows that our method provides significantly better results in anisotropic regions in 2-D and 3-D and is faster than current stat-of-the- art solvers in 2-D grids. Additionally, our method is straightforward to code; the test implementation is less than 150 lines of C++ code. The paper is an extension of a previously presented conference paper and includes new sections on 3-D grids in particular.

  17. Intracranial Volume Estimated with Commonly Used Methods Could Introduce Bias in Studies including Brain Volume Measurements
    Authors: Richard Nordenskjöld (1), Filip Malmberg, Elna-Marie Larsson (1), Andrew Simmons (2,3), Samatha J. Brooks (4), Lars Lind (5), Håkan Ahlström (1), Lars Johansson (1,6), Joel Kullberg (1)
    (1) Dept. Radiology, UU
    (2) King's College London, Institute of Psychiatry, London, UK
    (3) NIHR Biomedical Research Centre for Mental Health and NIHR Biomedical Research Unit for Dementia, London, UK
    (4) Dept. Neuroscience, UU
    (5) Dept. Medical Sciences, UU
    (6) AstraZeneca, Mölndal, Sweden
    Journal: NeuroImage, volume 83, pages 355-360
    Abstract: In brain volumetric studies, intracranial volume (ICV) is often used as an estimate of pre-morbid brain size as well as to compensate for inter-subject variations in head size. However, if the estimated ICV is biased by for example gender or atrophy, it could introduce errors in study results. To evaluate how two commonly used methods for ICV estimation perform, computer assisted reference segmentations were created and evaluated. Segmentations were created for 399 MRI volumes from 75-year-old subjects, with 53 of these subjects having an additional scan and segmentation created at age 80. ICV estimates from Statistical Parametric Mapping (SPM, version 8) and Freesurfer (FS, version 5.1.0) were compared to the reference segmentations, and bias related to skull size (approximated with the segmentation measure), gender or atrophy were tested for. The possible ICV related effect on associations between normalized hippocampal volume and factors gender, education and cognition was evaluated by normalizing hippocampal volume with different ICV measures. Excellent agreement was seen for inter- (r=0.999) and intra- (r=0.999) operator reference segmentations. Both SPM and FS overestimated ICV. SPM showed bias associated with gender and atrophy while FS showed bias dependent on skull size. All methods showed good correlation between time points in the longitudinal data (reference: 0.998, SPM: 0.962, FS: 0.995). Hippocampal volume showed different associations with cognition and gender depending on which ICV measure was used for hippocampal volume normalization. These results show that the choice of method used for ICV estimation can bias results in studies including brain volume measurements.

  18. Minimal-Delay Distance Transform for Neighborhood-Sequence Distances in 2D and 3D
    Authors: Nicolas Normand (1), Robin Strand, Pierre Evenou (1), Aurore Arlicot (1)
    (1) Institut de Recherche en Communications et en Cybernétique de Nantes (IRCCyN), France
    Journal: Computer Vision and Image Understanding, volume 117, number 4, pages 409-417
    Abstract: This paper presents a path-based distance, where local displacement costs vary both according to the displacement vector and with the travelled distance. The corresponding distance transform algorithm is similar in its form to classical propagation-based algorithms, but the more variable distance increments are either stored in look-up-tables or computed on-the-fly. These distances and distance transform extend neighborhood-sequence distances, chamfer distances and generalized distances based on Minkowski sums. We introduce algorithms to compute a translated version of a neighborhood sequence distance map both for periodic and aperiodic sequences and a method to derive the centered distance map. A decomposition of the grid neighbors, in and , allows to significantly decrease the number of displacement vectors needed for the distance transform. Overall, the distance transform can be computed with minimal delay, without the need to wait for the whole input image before beginning to provide the result image

  19. A Haptics-Assisted Cranio-Maxillofacial Surgery Planning System for Restoring Skeletal Anatomy in Complex Trauma Cases
    Authors: Pontus Olsson, Fredrik Nysjö, Jan-Michaél Hirsch (1), Ingrid B. Carlbom
    (1) Dept. Oral and Maxillofacial Surgery, UU
    Journal: International Journal of Computer Assisted Radiology and Surgery, volume 8, number 6, pages 887-894
    Abstract: Cranio-maxillofacial (CMF) surgery to restore normal skeletal anatomy in patients with serious trauma to the face can be both complex and time-consuming. But it is generally accepted that careful pre-operative planning leads to a better outcome with a higher degree of function and reduced morbidity in addition to reduced time in the operating room. However, today's surgery planning systems are primitive, relying mostly on the user's ability to plan complex tasks with a two-dimensional graphical interface. A system for planning the restoration of skeletal anatomy in facial trauma patients using a virtual model derived from patient-specific CT data. The system combines stereo visualization with six degrees-of-freedom, high-fidelity haptic feedback that enables analysis, planning, and preoperative testing of alternative solutions for restoring bone fragments to their proper positions. The stereo display provides accurate visual spatial perception, and the haptics system provides intuitive haptic feedback when bone fragments are in contact as well as six degrees-of-freedom attraction forces for precise bone fragment alignment. A senior surgeon without prior experience of the system received 45 min of system training. Following the training session, he completed a virtual reconstruction in 22 min of a complex mandibular fracture with an adequately reduced result. Preliminary testing with one surgeon indicates that our surgery planning system, which combines stereo visualization with sophisticated haptics, has the potential to become a powerful tool for CMF surgery planning. With little training, it allows a surgeon to complete a complex plan in a short amount of time.

  20. Adaptive Filtering for Enhancement of the Osteocyte Cell Network in 3D Microtomography Images
    Authors: Alexandra Pacureanu (1), A. Larrue (2), M. Langer (3,4), C. Olivier (3,4), C. Muller (3), M.-H.  Lafage-Proust, F. Peyrin(5)
    (1) Science for Life Laboratory, SciLifeLab, UU
    (2) Institute of Biomedical Engineering, University of Oxford, UK
    (3) Université de Lyon, France
    (4) European Synchrotron Radiation Facility (ESRF), Grenoble, France
    (5) Université Jean-Monnet, Saint-Étienne, France
    Journal: IRBM, volume 34, number 1-SI, pages 48-52
    Abstract: The osteocyte cell network in bone tissue is thought to orchestrate tissue adaptation and remodeling, thus holding responsibility for tissue quality. Previously, this structure has been studied mainly in 2D and its architecture and functions are not fully elucidated. The assessment of the osteocyte system is prerequisite for deeper understanding of bone remodeling and for advances in management of bone diseases. Our goal is to enable 3D isotropic imaging of bone at cellular level and to develop algorithms for quantitative image analysis of the cell network. We recently demonstrated accurate 3D imaging of this cell structure with synchrotron radiation tomography at submicrometric scale. Due to the limited spatial resolution of the imaging system and the constraints in terms of radiation dose, the images suffer from low signal to noise ratio and the detection of the cell dendrites is challenging. Here we detail a method for enhancement of the osteocyte network in human bone from 3D microtomography images. The approach combines Hessian-based 3D line enhancement and bilateral filtering. Our method enables extraction of the interconnected cells from noisy images, preserving the integrity of the cells and of their slender dendrites. Qualitative and quantitative results are presented.

  21. High-Throughput Hyperdimensional Vertebrate Phenotyping
    Authors: Carlos Pardo-Martin (1), Amin Allalou (1,2), Jaime Medina(1), Peter M. Eimon(1),Carolina Wählby (2,3), Mehmet Fatih Yanik (1,4)
    (1) Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA
    (2) Science for Life Laboratory, SciLifeLab, UU
    (3) Imaging Platform, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA
    (4) Department of Biological Engineering, MIT, Cambridge, MA, USA
    Journal: Nature Communications, volume 4, pages 1467
    Abstract: Most gene mutations and biologically active molecules cause complex responses in animals that cannot be predicted by cell culture models. Yet animal studies remain too slow and their analyses are often limited to only a few readouts. Here we demonstrate high-throughput optical projection tomography with micrometre resolution and hyperdimensional screening of entire vertebrates in tens of seconds using a simple fluidic system. Hundreds of independent morphological features and complex phenotypes are automatically captured in three dimensions with unprecedented speed and detail in semitransparent zebrafish larvae. By clustering quantitative phenotypic signatures, we can detect and classify even subtle alterations in many biological processes simultaneously. We term our approach hyperdimensional in vivo phenotyping. To illustrate the power of hyperdimensional in vivo phenotyping, we have analysed the effects of several classes of teratogens on cartilage formation using 200 independent morphological measurements, and identified similarities and differences that correlate well with their known mechanisms of actions in mammals

  22. Bisphenol a Exposure Increases Liver Fat in Juvenile Fructose-Fed Fischer 344 Rats
    Authors: Monika Rönn (1), Joel Kullberg (2), Helen Karlsson (3), Johan Berglund (2), Filip Malmberg, Jan Örberg (4), Lars Lind (5), Håkan Ahlström (2), P. Monica Lind (1)
    (1) Occupational and Environmental Medicine, UU
    (2) Dept. Radiology, UU
    (3) Occupational and Environmental Medicine, County Council of Östergötland, Linköping University
    (4) Dept. Organismal Biology, Environmental Toxicology, UU
    (5) Dept. Medical Sciences, UU
    Journal: Toxicology, volume 303, number 1, pages 125-132
    Abstract: Background: Prenatal exposure to bisphenol A (BPA) has been shown to induce obesity in rodents. To evaluate if exposure also later in life could induce obesity or liver damage we investigated these hypothesises in an experimental rat model.
    METHODS: From five to fifteen weeks of age, female Fischer 344 rats were exposed to BPA via drinking water (0.025, 0.25 or 2.5mgBPA/L) containing 5% fructose. Two control groups were given either water or 5% fructose solution. Individual weight of the rats was determined once a week. At termination magnetic resonance imaging was used to assess adipose tissue amount and distribution, and liver fat content. After sacrifice the left perirenal fat pad and the liver were dissected and weighed. Apolipoprotein A-I in plasma was analyzed by western blot.
    Results: No significant effects on body weight or the weight of the dissected fad pad were seen in rats exposed to BPA, and MRI showed no differences in total or visceral adipose tissue volumes between the groups. However, MRI showed that liver fat content was significantly higher in BPA-exposed rats than in fructose controls (p=0.04). BPA exposure also increased the apolipoprotein A-I levels in plasma (p<0.0001).
    Conclusion: We found no evidence that BPA exposure affects fat mass in juvenile fructose-fed rats. However, the finding that BPA in combination with fructose induced fat infiltration in the liver at dosages close to the current tolerable daily intake (TDI) might be of concern given the widespread use of this compound in our environment.

  23. Quantification of Total and Visceral Adipose Tissue in Fructose-Fed Rats Using Water-Fat Separated Single Echo MRI
    Authors: Monika Rönn (1), Monica P. Lind (1), Helen Karlsson (2), Katarina Cvek (3), Johan Berglund (4), Filip Malmberg, Jan Örberg (5), Lars Lind (6), Francisco Ortiz-Nieto (4), Joel Kullberg (4)
    (1) Occupational and Environmental Medicine, UU
    (2) Occupational and Environmental Medicine, County Council of Östergotland, Linköping University
    (3) Dept. Clinical Sciences, SLU, Uppsala
    (4) Dept. Radiology, Oncology, and Radiation Science, UU
    (5) Dept. Organismal Biology, Environmental Toxicology, UU
    (6) Dept. Medical Sciences, UU
    Journal: Obesity, volume 21, number 9, pages E388-395
    Abstract: Objective: The aim of this study was to setup a rodent model for modest weight gain and an MRI-based quantification of body composition on a clinical 1.5 T MRI system for studies of obesity and environmental factors and their possible association.
    Design and Methods: Twenty-four 4-week-old female Fischer rats were divided into two groups: one exposed group (n=12) and one control group (n 12). The exposed group was given drinking water containing fructose (5% for 7 weeks, then 20% for 3 weeks). The control group was given tap water. Before sacrifice, whole body MRI was performed to determine volumes of total and visceral adipose tissue and lean tissue. MRI was performed using a clinical 1.5 T system and a chemical shift based technique for separation of water and fat signal from a rapid single echo acquisition. Fat signal fraction was used to separate adipose and lean tissue. Visceral adipose tissue volume was quantified using semiautomated segmentation. After sacrifice, a perirenal fat pad and the liver were dissected and weighed. Plasma proteins were analyzed by Western blot.
    Results: The weight gain was 5.2% greater in rats exposed to fructose than in controls (P=0.042). Total and visceral adipose tissue volumes were 5.2 cm(3) (P=0.017) and 3.1 cm(3) (P=0.019) greater, respectively, while lean tissue volumes did not differ. The level of triglycerides and apolipoprotein A-I was higher (P=0.034, P=0.005, respectively) in fructose-exposed rats.

  24. Introducing a Novel Analysis Technique for Osseointegrated Dental Implants Retrieved 29 Years Postsurgery
    Authors: Hamid Sarve, Bertil Friberg (1), Gunilla Borgefors, Carina B. Johansson (2)
    (1) Brånemark Clinic, Göteborg, Sweden
    (2) Department of Prosthodontics/Dental Materials Science, Institute of Odontology, Göteborg University
    Journal: Clinical Implant Dentistry and Related Research, volume 15, number 4, pages 538-549
    Abstract: Purpose: To investigate osseointegration of oral implants, which were retrieved from a patient after 29 years in situ, we use novel three-dimensional analysis methods and visualization techniques that supplement conventional two-dimensional analysis. Materials and Methods: The sample processing involved nondecalcification and embedment in resin. Conventional two-dimensional histomorphometrical methods were conducted. Additionally, the quantification was extended to three-dimensional by using synchrotron radiation micro-computed tomography (SRmCT) technique and two relevant visualization methods for the three-dimensional data were introduced. Results: The three-dimensional results involved three-dimensional quantification and visualization of two implant samples with methods beyond state-of-the-art. Traditional two-dimensional histomorphometrical results revealed a mean bone-implant contact (BIC) of about 50%. In most samples, bone area (BA) was lower inside the treads compared with out-folded mirror images, which were confirmed by the three-dimensional quantification. The BIC along four selected regions showed highest percentages in the bottom/valley region and lowest in the thread-peak region. Qualitative observations revealed ongoing bone remodeling areas in all samples. The apical hole demonstrated high osseointegration. Conclusion: The novel techniques including an animation and an out-folding of BIC and BA enabled a simultaneous visualization of the three-dimensional material obtained from SRmCT data. However, the two-dimensional histological sections were needed for qualitative and quantitative evaluation of osseointegration and, thus, both methods are considered equally important.
  25. Evaluating 2D and 3D Geovisualisations for Basic Spatial Assessment
    Author: Stefan Seipel
    Journal: Behavior and Information Technology, volume 32, number 8, pages 845-858
    Abstract: This study investigates the use of 2D and 3D presentations of maps for the assessment of distances in a geographical context. Different types of 3D representations have been studied: A weak 3D visualisation that provides static monocular depth cues and a strong 3D visualisation that uses stereoscopic and kinetic depth cues. Two controlled experiments were conducted to test hypotheses regarding subjects' efficiency in visually identifying the shortest distance among a set of market locations in a map. As a general result, we found that participants were able to correctly identify shortest distances when the difference to potential alternatives was sufficiently large, but performance decreased systematically when this difference decreased. Noticeable differences emerged for the investigated visualisation conditions. Participants in this study were equally efficient when using a weak 3D representation and a 2D representation. When the strong 3D visualisation was employed, they reported visual discomfort and tasks solved were significantly less correct. Presentations of intrinsic 2D content (maps) in 3D context did not, in this study, benefit from cues provided by a strong 3D visualisation and are adequately implemented using a weak 3D visualisation.
  26. The Minimum Barrier Distance
    Authors: Robin Strand, Krzysztof Chris Ciesielski (1,2), Filip Malmberg, Punam K. Saha (3,4)
    (1) Dept. Mathematics, West Virginia University, Morgantown, WV, USA
    (2) Dept. Radiology, MIPG, University of Pennsylvania, Philadelphia, PA, USA
    (3) Dept. Electrical and Computer Engineering, The University of Iowa, Iowa City, IA, USA
    (4) Dept. Radiology, The University of Iowa, Iowa City, IA, USA
    Journal: Computer Vision and Image Understanding, volume 117, number 4, pages 429-437
    Abstract: In this paper we introduce a minimum barrier distance, MBD, defined for the (graphs of) real-valued bounded functions , whose domain is a compact subsets of the Euclidean space . The formulation of MBD is presented in the continuous setting, where is a simply connected region in , as well as in the case where is a digital scene. The MBD is defined as the minimal value of the barrier strength of a path between the points, which constitutes the length of the smallest interval containing all values of along the path. We present several important properties of MBD, including the theorems: on the equivalence between the MBD and its alternative definition ; and on the convergence of their digital versions, and , to the continuous MBD as we increase a precision of sampling. This last result provides an estimation of the discrepancy between the value of and of its approximation . An efficient computational solution for the approximation of is presented. We experimentally investigate the robustness of MBD to noise and blur, as well as its stability with respect to the change of a position of points within the same object (or its background). These experiments are used to compare MBD with other distance functions: fuzzy distance, geodesic distance, and max-arc distance. A favorable outcome for MBD of this comparison suggests that the proposed minimum barrier distance is potentially useful in different imaging tasks, such as image segmentation.
  27. 3D Tree-Ring Analysis Using Helical X-Ray Tomography
    Authors: Jan Van den Bulcke (1), Erik L. G. Wernersson, Manuel Dierick (2), Denis Van Loo (2), Bert Masschaele (2), Loes Brabant (2), Matthieu N. Boone 2), Luc Van Hoorebeke (2), Kristof Haneca(3), Anders Brun, Cris L. Luengo Hendriks, Joris Van Acker (1)
    (1) Dept. Forest and Water Management, Laboratory of Wood Technology, UGCT-Ghent University, Belgium
    (2) Dept. Physics and Astronomy, UGCT-Ghent University, Belgium
    (3) Flanders Heritage Agency, Brussels, Belgium
    Journal: Dendrochronologia, volume 32
    Abstract: The current state-of-the-art of tree-ring analysis and densitometry is still mainly limited to two dimensions and mostly requires proper treatment of the surface of the samples. In this paper we elaborate on the potential of helical X-ray computed tomography for 3D tree-ring analysis. Microdensitometrical profiles are obtained by processing of the reconstructed volumes. Correction of the structure direction, taking into account the angle of growth rings and grain, results in very accurate microdensity and precise ring width measurements. Both a manual as well as an automated methodology is proposed here, of which the MATLAB code is available. Examples are given for pine (Pinus sylvestris L.), oak (Quercus robur L.) and teak (Tectona grandis L.). In all, the methodologies applied here on the 3D volumes are useful for growth related studies, enabling a fast and non-destructive analysis
  28. Investigation of the Three-Dimensional Orientation of Mineralized Collagen Fibrils in Human Lamellar Bone Using Synchrotron X-Ray Phase Nano-Tomography
    Authors: Peter Varga (1), Alexandra Pacureanu (2,3,4), Max Langer (2,3), Heikki Suhonen (3), Bernhard Hesse (1,3), Quentin Grimal (5), Peter Cloetens (3), Kay Raum (1), Françoise Peyrin (2,3)
    (1) Julius Wolff Institute and Berlin-Brandenburg School for Regenerative Therapies, Charité Universitätsmedizin, Berlin, Germany
    (2) Creatis, Université de Lyon, France
    (3) European Synchrotron Radiation Facility, Grenoble, France
    (4) Science for Life Laboratory, SciLifeLab, UU
    (5) LIP, UPMC Université Pierre et Marie Curie Paris 6, Paris, France
    Journal: Acta Biomaterialia, volume 9, number 9, pages 8118-8127
    Abstract: We investigate the three-dimensional (3-D) organization of mineralized collagen fibrils in human cortical bone based on synchrotron X-ray phase nano-tomography images. In lamellar bone the collagen fibrils are assumed to have a plywood-like arrangement, but due to experimental limitations the 3-D fibril structure has only been deduced from section surfaces so far and the findings have been controversial. Breakthroughs in synchrotron tomographic imaging have given access to direct 3-D information on the bone structure at the nanoscale level. Using an autocorrelation-based orientation measure we confirm that the fibrils are unidirectional in quasi-planes of sub-lamellae and find two specific dominant patterns, oscillating and twisted plywoods coexisting in a single osteon. Both patterns exhibit smooth orientation changes between adjacent quasi-planes. Moreover, we find that the periodic changes in collagen fibril orientation are independent of fluctuations in local mass density. These data improve our understanding of the lamellar arrangement in bone and allow more detailed investigations of structure-function relationships at this scale, providing templates for bio-inspired materials. The presented methodology can be applied to non-destructive 3-D characterization of the sub-micron scale structure of other natural and artificial mineralized biomaterials.

  29. Postprocessing Method for Reducing Phase Effects in Reconstructed Microcomputed-Tomography Data
    Authors: Erik L. G. Wernersson, Matthieu N. Boone (1,2), Jan Van den Bulcke (1,3), Luc Van Hoorebeke (1,2), Cris L. Luengo Hendriks
    (1) UGCT, University Ghent Centre for X-ray Tomography, Belgium
    (2) Dept. Physics and Astronomy, Ghent University, Belgium
    (3) Dept. Forest and Water Management, Ghent University, Belgium
    Journal: Optical Society of America, Journal A, volume 30, number 3, pages 455-461
    Abstract: With increased resolution in x-ray computed tomography, refraction adds increasingly to the attenuation signal. Though potentially beneficial, the artifacts caused by refraction often need to be removed from the image. In this paper, we propose a postprocessing method, based on deconvolution, that is able to remove these artifacts after conventional reconstruction. This method poses two advantages over existing projection-based (preprocessing) phase-retrieval or phase-removal algorithms. First, evaluation of the parameters can be done very quickly, improving the overall speed of the method. Second, postprocessing methods can be applied when projection data is not available, which occurs in several commercial systems with closed software or when projection data has been deleted. It is shown that the proposed method performs comparably to state-of-the-art methods in terms of image quality.

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