Automatic clustering of white matter fibers in brain diffusion mri with an application to genetics

To understand factors that affect brain connectivity and integrity, it is beneficial to automatically cluster white matter (WM) fibers into anatomically recognizable tracts. Whole brain tractography, based on diffusion-weighted MRI, generates vast sets of fibers throughout the brain; clustering them into consistent and recognizable bundles can be difficult as there are wide individual variations in the trajectory and shape of WM pathways. Here we introduce a novel automated tract clustering algorithm based on label fusion - a concept from traditional intensity-based segmentation. Streamline tractography generates many incorrect fibers, so our top-down approach extracts tracts consistent with known anatomy, by mapping multiple hand-labeled atlases into a new dataset. We fuse clustering results from different atlases, using a mean distance fusion scheme. We reliably extracted the major tracts from 105-gradient high angular resolution diffusion images (HARDI) of 198 young normal twins. To compute population statistics, we use a pointwise correspondence method to match, compare, and average WM tracts across subjects. We illustrate our method in a genetic study of white matter tract heritability in twins.

Labeling white matter tracts in hardi by fusing multiple tract atlases with applications to genetics

Accurate identification of white matter structures and segmentation of fibers into tracts is important in neuroimaging and has many potential applications. Even so, it is not trivial because whole brain tractography generates hundreds of thousands of streamlines that include many false positive fibers. We developed and tested an automatic tract labeling algorithm to segment anatomically meaningful tracts from diffusion weighted images. Our multi-atlas method incorporates information from multiple hand-labeled fiber tract atlases. In validations, we showed that the method outperformed the standard ROI-based labeling using a deformable, parcellated atlas. Finally, we show a high-throughput application of the method to genetic population studies. We use the sub-voxel diffusion information from fibers in the clustered tracts based on 105-gradient HARDI scans of 86 young normal twins. The whole workflow shows promise for larger population studies in the future.

Heritability of white matter fiber tract shapes: A HARDI study of 198 twins

Genetic analysis of diffusion tensor images (DTI) shows great promise in revealing specific genetic variants that affect brain integrity and connectivity. Most genetic studies of DTI analyze voxel-based diffusivity indices in the image space (such as 3D maps of fractional anisotropy) and overlook tract geometry. Here we propose an automated workflow to cluster fibers using a white matter probabilistic atlas and perform genetic analysis on the shape characteristics of fiber tracts. We apply our approach to large study of 4-Tesla high angular resolution diffusion imaging (HARDI) data from 198 healthy, young adult twins (age: 20-30). Illustrative results show heritability for the shapes of several major tracts, as color-coded maps.

Automatic clustering and population analysis of white matter tracts using maximum density paths

We introduce a framework for population analysis of white matter tracts based on diffusion-weighted images of the brain. The framework enables extraction of fibers from high angular resolution diffusion images (HARDI); clustering of the fibers based partly on prior knowledge from an atlas; representation of the fiber bundles compactly using a path following points of highest density (maximum density path; MDP); and registration of these paths together using geodesic curve matching to find local correspondences across a population. We demonstrate our method on 4-Tesla HARDI scans from 565 young adults to compute localized statistics across 50 white matter tracts based on fractional anisotropy (FA). Experimental results show increased sensitivity in the determination of genetic influences on principal fiber tracts compared to the tract-based spatial statistics (TBSS) method. Our results show that the MDP representation reveals important parts of the white matter structure and considerably reduces the dimensionality over comparable fiber matching approaches.

Curing, defects and mechanical performance of fiber-reinforced composites

Tradicionalmente, la fabricación de materiales compuestos de altas prestaciones se lleva a cabo en autoclave mediante la consolidación de preimpregnados a través de la aplicación simultánea de altas presiones y temperatura. Las elevadas presiones empleadas en autoclave reducen la porosidad de los componentes garantizando unas buenas propiedades mecánicas. Sin embargo, este sistema de fabricación conlleva tiempos de producción largos y grandes inversiones en equipamiento lo que restringe su aplicación a otros sectores alejados del sector aeronáutico. Este hecho ha generado una creciente demanda de sistemas de fabricación alternativos al autoclave. Aunque estos sistemas son capaces de reducir los tiempos de producción y el gasto energético, por lo general, dan lugar a materiales con menores prestaciones mecánicas debido a que se reduce la compactación del material al aplicar presiones mas bajas y, por tanto, la fracción volumétrica de fibras, y disminuye el control de la porosidad durante el proceso. Los modelos numéricos existentes permiten conocer los fundamentos de los mecanismos de crecimiento de poros durante la fabricación de materiales compuestos de matriz polimérica mediante autoclave. Dichos modelos analizan el comportamiento de pequeños poros esféricos embebidos en una resina viscosa. Su validez no ha sido probada, sin embargo, para la morfología típica observada en materiales compuestos fabricados fuera de autoclave, consistente en poros cilíndricos y alargados embebidos en resina y rodeados de fibras continuas. Por otro lado, aunque existe una clara evidencia experimental del efecto pernicioso de la porosidad en las prestaciones mecánicas de los materiales compuestos, no existe información detallada sobre la influencia de las condiciones de procesado en la forma, fracción volumétrica y distribución espacial de los poros en los materiales compuestos. Las técnicas de análisis convencionales para la caracterización microestructural de los materiales compuestos proporcionan información en dos dimensiones (2D) (microscopía óptica y electrónica, radiografía de rayos X, ultrasonidos, emisión acústica) y sólo algunas son adecuadas para el análisis de la porosidad. En esta tesis, se ha analizado el efecto de ciclo de curado en el desarrollo de los poros durante la consolidación de preimpregnados Hexply AS4/8552 a bajas presiones mediante moldeo por compresión, en paneles unidireccionales y multiaxiales utilizando tres ciclos de curado diferentes. Dichos ciclos fueron cuidadosamente diseñados de acuerdo a la caracterización térmica y reológica de los preimpregnados. La fracción volumétrica de poros, su forma y distribución espacial se analizaron en detalle mediante tomografía de rayos X. Esta técnica no destructiva ha demostrado su capacidad para analizar la microestructura de materiales compuestos. Se observó, que la porosidad depende en gran medida de la evolución de la viscosidad dinámica a lo largo del ciclo y que la mayoría de la porosidad inicial procedía del aire atrapado durante el apilamiento de las láminas de preimpregnado. En el caso de los laminados multiaxiales, la porosidad también se vio afectada por la secuencia de apilamiento. En general, los poros tenían forma cilíndrica y se estaban orientados en la dirección de las fibras. Además, la proyección de la población de poros a lo largo de la dirección de la fibra reveló la existencia de una estructura celular de un diámetro aproximado de 1 mm. Las paredes de las celdas correspondían con regiones con mayor densidad de fibra mientras que los poros se concentraban en el interior de las celdas. Esta distribución de la porosidad es el resultado de una consolidación no homogenea. Toda esta información es crítica a la hora de optimizar las condiciones de procesado y proporcionar datos de partida para desarrollar herramientas de simulación de los procesos de fabricación de materiales compuestos fuera de autoclave. Adicionalmente, se determinaron ciertas propiedades mecánicas dependientes de la matriz termoestable con objeto de establecer la relación entre condiciones de procesado y las prestaciones mecánicas. En el caso de los laminados unidireccionales, la resistencia interlaminar depende de la porosidad para fracciones volumétricas de poros superiores 1%. Las mismas tendencias se observaron en el caso de GIIc mientras GIc no se vio afectada por la porosidad. En el caso de los laminados multiaxiales se evaluó la influencia de la porosidad en la resistencia a compresión, la resistencia a impacto a baja velocidad y la resistencia a copresión después de impacto. La resistencia a compresión se redujo con el contenido en poros, pero éste no influyó significativamente en la resistencia a compresión despues de impacto ya que quedó enmascarada por otros factores como la secuencia de apilamiento o la magnitud del daño generado tras el impacto. Finalmente, el efecto de las condiciones de fabricación en el proceso de compactación mediante moldeo por compresión en laminados unidireccionales fue simulado mediante el método de los elementos finitos en una primera aproximación para simular la fabricación de materiales compuestos fuera de autoclave. Los parámetros del modelo se obtuvieron mediante experimentos térmicos y reológicos del preimpregnado Hexply AS4/8552. Los resultados obtenidos en la predicción de la reducción de espesor durante el proceso de consolidación concordaron razonablemente con los resultados experimentales. Manufacturing of high performance polymer-matrix composites is normally carried out by means of autoclave using prepreg tapes stacked and consolidated under the simultaneous application of pressure and temperature. High autoclave pressures reduce the porosity in the laminate and ensure excellent mechanical properties. However, this manufacturing route is expensive in terms of capital investment and processing time, hindering its application in many industrial sectors. This fact has driven the demand of alternative out-of-autoclave processing routes. These techniques claim to produce composite parts faster and at lower cost but the mechanical performance is also reduced due to the lower fiber content and to the higher porosity. Corrient numerical models are able to simulate the mechanisms of void growth in polymer-matrix composites processed in autoclave. However these models are restricted to small spherical voids surrounded by a viscous resin. Their validity is not proved for long cylindrical voids in a viscous matrix surrounded by aligned fibers, the standard morphology observed in out-of-autoclave composites. In addition, there is an experimental evidence of the detrimental effect of voids on the mechanical performance of composites but, there is detailed information regarding the influence of curing conditions on the actual volume fraction, shape and spatial distribution of voids within the laminate. The standard techniques of microstructural characterization of composites (optical or electron microscopy, X-ray radiography, ultrasonics) provide information in two dimensions and are not always suitable to determine the porosity or void population. Moreover, they can not provide 3D information. The effect of curing cycle on the development of voids during consolidation of AS4/8552 prepregs at low pressure by compression molding was studied in unidirectional and multiaxial panels. They were manufactured using three different curing cycles carefully designed following the rheological and thermal analysis of the raw prepregs. The void volume fraction, shape and spatial distribution were analyzed in detail by means of X-ray computed microtomography, which has demonstrated its potential for analyzing the microstructural features of composites. It was demonstrated that the final void volume fraction depended on the evolution of the dynamic viscosity throughout the cycle. Most of the initial voids were the result of air entrapment and wrinkles created during lay-up. Differences in the final void volume fraction depended on the processing conditions for unidirectional and multiaxial panels. Voids were rod-like shaped and were oriented parallel to the fibers and concentrated in channels along the fiber orientation. X-ray computer tomography analysis of voids along the fiber direction showed a cellular structure with an approximate cell diameter of 1 mm. The cell walls were fiber-rich regions and porosity was localized at the center of the cells. This porosity distribution within the laminate was the result of inhomogeneous consolidation. This information is critical to optimize processing parameters and to provide inputs for virtual testing and virtual processing tools. In addition, the matrix-controlled mechanical properties of the panels were measured in order to establish the relationship between processing conditions and mechanical performance. The interlaminar shear strength (ILSS) and the interlaminar toughness (GIc and GIIc) were selected to evaluate the effect of porosity on the mechanical performance of unidirectional panels. The ILSS was strongly affected by the porosity when the void contents was higher than 1%. The same trends were observed in the case of GIIc while GIc was insensitive to the void volume fraction. Additionally, the mechanical performance of multiaxial panels in compression, low velocity impact and compression after impact (CAI) was measured to address the effect of processing conditions. The compressive strength decreased with porosity and ply-clustering. However, the porosity did not influence the impact resistance and the coompression after impact strength because the effect of porosity was masked by other factors as the damage due to impact or the laminate lay-up. Finally, the effect of the processing conditions on the compaction behavior of unidirectional AS4/8552 panels manufactured by compression moulding was simulated using the finite element method, as a first approximation to more complex and accurate models for out-of autoclave curing and consolidation of composite laminates. The model parameters were obtained from rheological and thermo-mechanical experiments carried out in raw prepreg samples. The predictions of the thickness change during consolidation were in reasonable agreement with the experimental results.

Optimization of curing cycle in carbon fiber-reinforced laminates: Void distribution and mechanical properties

A strategy is presented to optimize out-of-autoclave processing of quasi-isotropic carbon fiber-reinforced laminates. Square panels of 4.6 mm nominal thickness with very low porosity ð6 0:2%Þ were manufactured by compression molding at low pressure (0.2 MPa) by careful design of the temperature cycle to maximize the processing window. The mechanisms of void migration during processing were ascertained by means of X-ray microtomography and the effect of ply clustering on porosity and on void shape was explained. Finally, the effect of porosity and ply clustering on the compressive strength before and after impact was studied.

Activity-dependent regulation of synaptic clustering in a hippocampal culture system

Currently, there is a limited understanding of the factors that influence the localization and density of individual synapses in the central nervous system. Here we have studied the effects of activity on synapse formation between hippocampal dentate granule cells and CA3 pyramidal neurons in culture, taking advantage of FM1–43 as a fluorescent marker of synaptic boutons. We observed an early tendency for synapses to group together, quickly followed by the appearance of synaptic clusters on dendritic processes. These events were strongly influenced by N-methyl-d-aspartic acid receptor- and cyclic AMP-dependent signaling. The microstructure and localization of the synaptic clusters resembled that found in hippocampus, at mossy fiber synapses of stratum lucidum. Activity-dependent clustering of synapses represents a means for synaptic targeting that might contribute to synaptic organization in the brain.