A Generative Model for the Joint Registration of Multiple Point Sets

International audienceThis paper describes a probabilistic generative model and its associated algorithm to jointly register multiple point sets. The vast majority of state-of-the-art registration techniques select one of the sets as the ''model" and perform pairwise alignments between the other sets and this set. The main drawback of this mode of operation is that there is no guarantee that the model-set is free of noise and outliers, which contaminates the estimation of the registration parameters. Unlike previous work, the proposed method treats all the point sets on an equal footing: they are realizations of a Gaussian mixture (GMM) and the registration is cast into a clustering problem. We formally derive an EM algorithm that estimates both the GMM parameters and the rotations and translations that map each individual set onto the ''central" model. The mixture means play the role of the registered set of points while the variances provide rich information about the quality of the registration. We thoroughly validate the proposed method with challenging datasets, we compare it with several state-of-the-art methods, and we show its potential for fusing real depth data

Visualization of Inflammation in Experimental Colitis by Magnetic Resonance Imaging Using Very Small Superparamagnetic Iron Oxide Particles

Inflammatory bowel diseases (IBD) comprise mainly ulcerative colitis (UC) and Crohn´s disease (CD). Both forms present with a chronic inflammation of the (gastro) intestinal tract, which induces excessive changes in the composition of the associated extracellular matrix (ECM). In UC, the inflammation is limited to the colon, whereas it can occur throughout the entire gastrointestinal tract in CD. Tools for early diagnosis of IBD are still very limited and highly invasive and measures for standardized evaluation of structural changes are scarce. To investigate an efficient non-invasive way of diagnosing intestinal inflammation and early changes of the ECM, very small superparamagnetic iron oxide nanoparticles (VSOPs) in magnetic resonance imaging (MRI) were applied in two mouse models of experimental colitis: the dextran sulfate sodium (DSS)-induced colitis and the transfer model of colitis. For further validation of ECM changes and inflammation, tissue sections were analyzed by immunohistochemistry. For in depth ex-vivo investigation of VSOPs localization within the tissue, Europium-doped VSOPs served to visualize the contrast agent by imaging mass cytometry (IMC). VSOPs accumulation in the inflamed colon wall of DSS-induced colitis mice was visualized in T2* weighted MRI scans. Components of the ECM, especially the hyaluronic acid content, were found to influence VSOPs binding. Using IMC, co-localization of VSOPs with macrophages and endothelial cells in colon tissue was shown. In contrast to the DSS model, colonic inflammation could not be visualized with VSOP-enhanced MRI in transfer colitis. VSOPs present a potential contrast agent for contrast-enhanced MRI to detect intestinal inflammation in mice at an early stage and in a less invasive manner depending on hyaluronic acid content

Shape-aware surface reconstruction from sparse 3D point-clouds.

The reconstruction of an object's shape or surface from a set of 3D points plays an important role in medical image analysis, e.g. in anatomy reconstruction from tomographic measurements or in the process of aligning intra-operative navigation and preoperative planning data. In such scenarios, one usually has to deal with sparse data, which significantly aggravates the problem of reconstruction. However, medical applications often provide contextual information about the 3D point data that allow to incorporate prior knowledge about the shape that is to be reconstructed. To this end, we propose the use of a statistical shape model (SSM) as a prior for surface reconstruction. The SSM is represented by a point distribution model (PDM), which is associated with a surface mesh. Using the shape distribution that is modelled by the PDM, we formulate the problem of surface reconstruction from a probabilistic perspective based on a Gaussian Mixture Model (GMM). In order to do so, the given points are interpreted as samples of the GMM. By using mixture components with anisotropic covariances that are "oriented" according to the surface normals at the PDM points, a surface-based fitting is accomplished. Estimating the parameters of the GMM in a maximum a posteriori manner yields the reconstruction of the surface from the given data points. We compare our method to the extensively used Iterative Closest Points method on several different anatomical datasets/SSMs (brain, femur, tibia, hip, liver) and demonstrate superior accuracy and robustness on sparse data

Robustness and Accuracy of Feature-Based Single Image 2-D–3-D Registration Without Correspondences for Image-Guided Intervention

published_or_final_versio

NUTRIENT CYCLING ALONG MICROBIAL AND LITHOLOGIC GRADIENTS AND FOSTERING STUDENT SELF-CONFIDENCE IN SCIENCE

Increased understanding of the impact of biology on weathering rates and its response to environmental factors will lead to more accurate global models and enhanced management practices to optimize productive, healthy forests. Although biological contributions to weathering are established in the literature, more data to translate these observations for implementation in a predictive framework should be obtained (e.g. Taylor et al., 2012). Mycorrhizal fungi have implications for global carbon cycling and increasing carbon storage in soils (Soudzilovskaia et al., 2019) but the extent of their impact is still an area of active research with more studies of local weathering sites still needed (Finlay et al., 2020; Terrer et al., 2016; Norby et al., 2017). This dissertation examines the role that microbes can have on moderating mineral weathering and nutrient cycling in terrestrial ecosystems. My research combines geochemical data from two field studies and one controlled growth experiment with prokaryotic community composition data to determine how rock type can drive microbial weathering. Results from the two field studies, the latter including microbial community data, suggest that weathering fluxes in forest stands with different dominant mycorrhizal vegetation may be more similar than previously thought and that abiotic factors and rock composition may be responsible for weathering fluxes at the field scale. The growth chamber experiment allowed me to examine two mycorrhizal symbioses across two distinct lithologies in a controlled environment and the results suggest that mycorrhizal weathering, especially that of AM fungi, may be enhanced when nutrients aren’t readily available. Overall this work helps use to constrain the importance of biological weathering. In the final section of my dissertation I shift my focus to look at how scientists can help engage students in authentic science practice and how this experience might build students’ self-confidence in science. I examined an established citizen science program, NASA GLOBE, and focused on how students participation in collecting data using GLOBE protocols, analyzing and reporting it, and communicating this to peers at scientists at the Student Research Symposium (SRS) helped shape students views of themselves and their confidence with science practices. Attending the SRS was seen to have a significant impact on students’ confidence in their ability to practice science (ex. “I am able to construct scientific arguments”) and their belief that they are “good at science”. I hope this work offers an example to other citizen science programs of components that can be used to engage students and improve their confidence in science

Harnessing Wharton's jelly stem cell differentiation into bone-like nodule on calcium phosphate substrate without osteoinductive factors.

An important aim of bone regenerative medicine is to design biomaterials with controlled chemical and topographical features to guide stem cell fate towards osteoblasts without addition of specific osteogenic factors. Herein, we find that sprayed bioactive and biocompatible calcium phosphate substrates (CaP) with controlled topography induce, in a well-orchestrated manner, Wharton's jelly stem cells (WJ-SCs) differentiation into osteoblastic lineage without any osteogenic supplements. The resulting WJ-SCs commitment exhibits features of native bone, through the formation of three-dimensional bone-like nodule with osteocyte-like cells embedded into a mineralized type I collagen. To our knowledge, these results present the first observation of a whole differentiation process from stem cell to osteocytes-like on a synthetic material. This suggests a great potential of sprayed CaP and WJ-SCs in bone tissue engineering. These unique features may facilitate the transition from bench to bedside and the development of successful engineered bone.Designing materials to direct stem cell fate has a relevant impact on stem cell biology and provides insights facilitating their clinical application in regenerative medicine. Inspired by natural bone compositions, a friendly automated spray-assisted system was used to build calcium phosphate substrate (CaP). Sprayed biomimetic solutions using mild conditions led to the formation of CaP with controlled physical properties, good bioactivity and biocompatibility. Herein, we show that via optimization of physical properties, CaP substrate induce osteogenic differentiation of Wharton's jelly stem cells (WJ-SCs) without adding osteogenic supplement factors. These results suggest a great potential of sprayed CaP and WJ-SCs in bone tissue engineering and may facilitate the transition from bench to beside and the development of clinically successful engineered bone.journal articleresearch support, non-u.s. gov't2017 022016 11 22importe

A 3D cephalometric protocol for the accurate quantification of the craniofacial symmetry and facial growth

© 2019 The Author(s). Background: Cephalometric analysis is used to evaluate facial growth, to study the anatomical relationships within the face. Cephalometric assessment is based on 2D radiographic images, either the sagittal or coronal planes and is an inherently inaccurate methodology. The wide availability of 3D imaging techniques, such as computed tomography and magnetic resonance imaging make routine 3D analysis of facial morphology feasible. 3D cephalometry may not only provide a more accurate quantification of the craniofacial morphology and longitudinal growth, but also the differentiation of subtle changes in occlusion. However, a reliable protocol for the computation of craniofacial symmetry and quantification of craniofacial morphology is still a topic of extensive research. Here, a protocol for 3D cephalometric analysis for both the identification of the natural head position (NHP) and the accurate quantification of facial growth and facial asymmetry is proposed and evaluated. A phantom study was conducted to assess the performance of the protocol and to quantify the ability to repeatedly and reliably align skulls with the NHP and quantify the degree of accuracy with which facial growth and facial asymmetry can be measured. Results: The results obtained show that the protocol allows consistent alignment with the NHP, with an overall average error (and standard deviation) of just 0.17 (9.10e-6) mm, with variations of 0.21 (2.77e-17) mm in the frontonasal suture and 0.30 (5.55e-17) mm in the most prominent point in the chin. The average errors associated with simulated facial growth ranged from 1.83 to 3.75% for 2 years' growth and from - 9.57 to 14.69% for 4 years, while the error in the quantification of facial asymmetry ranged from - 11.38 to 9.31%. Conclusions: The protocol for 3D skull alignment produces accurate and landmark free estimation of the true symmetry of the head. It allows a reliable alignment of the skull in the NHP independently of user-defined landmarks, as well as an accurate quantification of facial growth and asymmetry

Entwicklung der multifrequenten Magnetresonanz-Elastographie zur Quantifizierung der biophysikalischen Eigenschaften von menschlichem Hirngewebe

Magnetic resonance elastography (MRE) is an emerging technique for the quantitative imaging of the biophysical properties of soft tissues in humans. Following its successful clinical application in detecting and characterizing liver fibrosis, the scientific community is investigating the use of viscoelasticity as a biomarker for neurological diseases. Clinical implementation requires a thorough understanding of brain tissue mechanics in conjunction with innovative techniques in new research areas. Therefore, three in vivo studies were conducted to analyze the inherent stiffness dispersion of brain tissue over a wide frequency range, to investigate real-time MRE in monitoring the viscoelastic response of brain tissue during the Valsalva maneuver (VM), and to study mechanical alterations of small lesions in multiple sclerosis (MS). Ultra-low frequency MRE with profile-based wave analysis was developed in 14 healthy subjects to determine large-scale brain stiffness, from pulsation-induced shear waves (1 Hz) to ultra-low frequencies (5 – 10 Hz) to the conventional range (20 – 40 Hz). Furthermore, multifrequency real-time MRE with a frame rate of 5.4 Hz was introduced to analyze stiffness and fluidity changes in response to respiratory challenges and cerebral autoregulation in 17 healthy subjects. 2D and 3D wavenumber-based stiffness reconstruction of the brain was established for conventional MRE in 12 MS patients. MS lesions were analyzed in terms of mechanical contrast with surrounding tissue in relation to white matter (WM) heterogeneity. We found superviscous properties of brain tissue at large scales with a strong stiffness dispersion and a relatively high model-based viscosity of η = 6.6 ± 0.3 Pa∙s. The brain’s viscoelasticity was affected by perfusion changes during VM, which was associated with an increase in brain stiffness of 6.7% ± 4.1% (p<.001), whereas fluidity decreased by -2.1 ± 1.4% (p<.001). In the diseased brain, the analysis of 147 MS lesions revealed 46% of lesions to be softer and 54% of lesions to be stiffer than surrounding tissue. However, due to the heterogeneity of WM stiffness, the results provide no significant evidence for a systematic pattern of mechanical variations in MS. Nevertheless, the results may explain, for the first time, the gap between static ex vivo and dynamic in vivo methods. Fluidity-induced dispersion provides rich information on the structure of tissue compartments. Moreover, viscoelasticity is affected by perfusion during cerebral autoregulation and thus may be sensitive to intracranial pressure modulation. The overall heterogeneity of stiffness obscures changes in MS lesions, and MS may not exhibit sclerosis as a mechanical signature. In summary, this thesis contributes to the field of human brain MRE by presenting new methods developed in studies conducted in new research areas using state-of-the-art technology. The results advance clinical applications and open exciting possibilities for future in vivo studies of human brain tissue.Die Magnetresonanz-Elastographie (MRE) ist ein Verfahren zur quantitativen Darstellung der viskoelastischen Eigenschaften von Weichgewebe. Nach der erfolgreichen klinischen Anwendung in der Leberdiagnostik wird versucht, Viskoelastizität als Biomarker für neurologische Krankheiten zu nutzen. Hierzu bedarf es einer genauen Analyse der Gewebemechanik und innovativen Anwendungsgebieten. Daher, wurden drei Studien durchgeführt, um die Steifigkeitsdispersion von Hirngewebe zu analysieren, das viskoelastische Verhalten während des Valsalva Manövers (VM) abzubilden, und die mechanischen Veränderungen in Läsionen bei Multipler Sklerose (MS) zu untersuchen. Niedrigfrequenz-MRE mit profilbasierter Wellenanalyse wurde in 14 Probanden entwickelt, um die Steifigkeit des Gesamthirns von pulsationsinduzierten Scherwellen (1 Hz) über ultraniedrige Frequenzen (5 – 10 Hz) bis hin zum konventionellen Bereich (20 – 40 Hz) zu bestimmen. Außerdem wurde die multifrequente Echtzeit-MRE mit einer Bildfrequenz von 6.4 Hz eingeführt, um die viskoelastische Antwort des Gehirns auf respiratorische Herausforderungen bei 17 gesunden Probanden zu untersuchen. Neue 2D- und 3D-Wellenzahl-basierte Steifigkeitsrekonstruktionen für das Gehirn wurden in 12 MS Patienten und konventioneller MRE entwickelt. Die Steifigkeitsänderungen in MS-Läsionen wurden mit umliegender weißer Substanz und dessen Heterogenität verglichen. Wir fanden superviskose Eigenschaften des Hirngewebes mit einer starken Dispersion und relativ hohen, modellbasierten Viskosität von η = 6,6 ± 0,3 Pa∙s. Die mechanischen Gewebeeigenschaften wurden durch Perfusionsänderungen während VM beeinflusst und die Hirnsteifigkeit erhöhte sich um 6,7 ± 4,1% (p<.001) wobei sich die Fluidität um -2,1 ± 1,4% (p<.001) verringerte. Die Analyse von 147 MS-Läsionen ergab, dass 54% bzw. 46% der Läsionen steifer bzw. weicher sind als das umgebende Gewebe. Aufgrund der Heterogenität der WM-Steifigkeit konnte jedoch kein Hinweis auf ein systematisches Muster mechanischer Veränderungen in MS-Läsionen gefunden werden. Die Ergebnisse können zum ersten Mal die Lücke zwischen statischen ex vivo und dynamischen in vivo Methoden erklären. Die fluiditätsinduzierte Dispersion liefert interessante Informationen über die zugrundeliegende Gewebestruktur. Darüber hinaus wird die Viskoelastizität durch die Perfusion während der zerebralen Autoregulation beeinflusst und kann daher empfindlich auf intrakranielle Druckschwankungen reagieren. Die allgemeine Heterogenität der Steifigkeit überschattet die Veränderungen in MS-Läsionen, und somit ist Sklerose möglicherweise kein prominentes Merkmal von MS. Zusammenfassend lässt sich festhalten, dass diese Dissertation einen Beitrag zum Gebiet der MRE leistet, indem neue Methoden und Anwendungen in neuen Forschungsgebieten mit modernster Technologie dargestellt werden. Hierdurch wird die klinische Translation gefördert und spannende Möglichkeiten für zukünftige Studien eröffnet

Graph matching using position coordinates and local features for image analysis

Encontrar las correspondencias entre dos imágenes es un problema crucial en el campo de la visión por ordenador i el reconocimiento de patrones. Es relevante para un amplio rango de propósitos des de aplicaciones de reconocimiento de objetos en las áreas de biometría, análisis de documentos i análisis de formas hasta aplicaciones relacionadas con la geometría desde múltiples puntos de vista tales cómo la recuperación de la pose, estructura desde el movimiento y localización y mapeo. La mayoría de las técnicas existentes enfocan este problema o bien usando características locales en la imagen o bien usando métodos de registro de conjuntos de puntos (o bien una mezcla de ambos). En las primeras, un conjunto disperso de características es primeramente extraído de las imágenes y luego caracterizado en la forma de vectores descriptores usando evidencias locales de la imagen. Las características son asociadas según la similitud entre sus descriptores. En las segundas, los conjuntos de características son considerados cómo conjuntos de puntos los cuales son asociados usando técnicas de optimización no lineal. Estos son procedimientos iterativos que estiman los parámetros de correspondencia y de alineamiento en pasos alternados. Los grafos son representaciones que contemplan relaciones binarias entre las características. Tener en cuenta relaciones binarias al problema de la correspondencia a menudo lleva al llamado problema del emparejamiento de grafos. Existe cierta cantidad de métodos en la literatura destinados a encontrar soluciones aproximadas a diferentes instancias del problema de emparejamiento de grafos, que en la mayoría de casos es del tipo "NP-hard". El cuerpo de trabajo principal de esta tesis está dedicado a formular ambos problemas de asociación de características de imagen y registro de conjunto de puntos como instancias del problema de emparejamiento de grafos. En todos los casos proponemos algoritmos aproximados para solucionar estos problemas y nos comparamos con un número de métodos existentes pertenecientes a diferentes áreas como eliminadores de "outliers", métodos de registro de conjuntos de puntos y otros métodos de emparejamiento de grafos. Los experimentos muestran que en la mayoría de casos los métodos propuestos superan al resto. En ocasiones los métodos propuestos o bien comparten el mejor rendimiento con algún método competidor o bien obtienen resultados ligeramente peores. En estos casos, los métodos propuestos normalmente presentan tiempos computacionales inferiores.Trobar les correspondències entre dues imatges és un problema crucial en el camp de la visió per ordinador i el reconeixement de patrons. És rellevant per un ampli ventall de propòsits des d’aplicacions de reconeixement d’objectes en les àrees de biometria, anàlisi de documents i anàlisi de formes fins aplicacions relacionades amb geometria des de múltiples punts de vista tals com recuperació de pose, estructura des del moviment i localització i mapeig. La majoria de les tècniques existents enfoquen aquest problema o bé usant característiques locals a la imatge o bé usant mètodes de registre de conjunts de punts (o bé una mescla d’ambdós). En les primeres, un conjunt dispers de característiques és primerament extret de les imatges i després caracteritzat en la forma de vectors descriptors usant evidències locals de la imatge. Les característiques son associades segons la similitud entre els seus descriptors. En les segones, els conjunts de característiques son considerats com conjunts de punts els quals son associats usant tècniques d’optimització no lineal. Aquests son procediments iteratius que estimen els paràmetres de correspondència i d’alineament en passos alternats. Els grafs son representacions que contemplen relacions binaries entre les característiques. Tenir en compte relacions binàries al problema de la correspondència sovint porta a l’anomenat problema de l’emparellament de grafs. Existeix certa quantitat de mètodes a la literatura destinats a trobar solucions aproximades a diferents instàncies del problema d’emparellament de grafs, el qual en la majoria de casos és del tipus “NP-hard”. Una part del nostre treball està dedicat a investigar els beneficis de les mesures de ``bins'' creuats per a la comparació de característiques locals de les imatges. La resta està dedicat a formular ambdós problemes d’associació de característiques d’imatge i registre de conjunt de punts com a instàncies del problema d’emparellament de grafs. En tots els casos proposem algoritmes aproximats per solucionar aquests problemes i ens comparem amb un nombre de mètodes existents pertanyents a diferents àrees com eliminadors d’“outliers”, mètodes de registre de conjunts de punts i altres mètodes d’emparellament de grafs. Els experiments mostren que en la majoria de casos els mètodes proposats superen a la resta. En ocasions els mètodes proposats o bé comparteixen el millor rendiment amb algun mètode competidor o bé obtenen resultats lleugerament pitjors. En aquests casos, els mètodes proposats normalment presenten temps computacionals inferiors

Intracerebral Implantation of ECM Hydrogel for the Treatment of Stroke

Stroke is the leading cause of serious, long-term disability affecting nearly 15 million people worldwide each year. After stroke, the hypoxic death of cells results in liquefactive necrosis of the damaged tissue. One of the key challenges in treating chronic stroke is the dramatic loss of brain tissue, and the formation of a cavity filled with extracellular fluid (ECF). Physical therapy and intracerebral implantation of cells has shown limited success in improving motor dysfunction, however there is no replacement of the lost tissue and hence a large tissue cavity remains in the brains of stroke survivors. Extracellular matrix (ECM), which fills the space between the cells, makes up 20% of the whole brain tissue volume and contains proteins such as laminin, fibronectin, myelin and growth factors. The objectives of this work were to determine if hydrogels composed of decellularized mammalian ECM implanted in a stroke cavity promotes cellular infiltration and constructive tissue remodeling, as well as optimization of 19F MR imaging to visualize the peripheral macrophages invading the lesion cavity. At ECM concentrations that have similar rheological properties as brain tissue, the ECM exists in fluid phase at room temperature, while forming hydrogels at body temperature. However, large volumes of hydrogel injection into the lesion cavity will increase the intracerebral pressure and further damage brain tissue. Using non-invasive magnetic resonance imaging (MRI)-guidance, the hydrogel can be reliably delivered to the lesion cavity, while draining the ECF through another cannula. We evaluated histologically 0, 3, 4 and 8 mg/mL of porcine-derived urinary bladder matrix (UBM)-ECM hydrogel concentrations implanted in a 14-day old stroke cavity. Less concentrated hydrogels (3 and 4 mg/mL) were efficiently degraded with a 95% decrease in volume by 90 days, whereas only 32% of the more concentrated and stiffer hydrogel (8 mg/mL) was resorbed. The less concentrated hydrogels showed a robust invasion of endothelial cells that supported neovascularization. No neovascularization occurred with the stiffer hydrogel. Invasion of neural cells increased with time in all hydrogel concentrations. Differentiation of neural progenitors into mature neurons with axonal projections was evident, as well as a robust invasion of oligodendrocytes. Macrophage infiltration and density within the bioscaffold affected the hydrogel biodegradation and progressively increased in the less concentrated hydrogels and decreased in the 8 mg/mL hydrogels. Optimization of 19F imaging parameters revealed fast imaging with steady state precession (FISP) sequence being the most efficient for the detection of perfluorocarbons (PFCs). In vivo 19F MRI shows robust visualization of peripheral macrophages invading the lesion cavity implanted with 4 mg/mL ECM hydrogel. Intravenous administration of PFCs results in accumulation of 19F labeled cells within the ECM hydrogel and in the peri-infarct tissue. Histological analysis at 1 day post-injection revealed all infiltrating Iba1+ cells to also be 19F labeled, indicating that these are peripheral macrophages rather than brain derived microglia. This body of work demonstrates that implantation of an ECM hydrogel induced neural tissue regeneration, but a more complete understanding is required to evaluate its potential therapeutic application