Volume Haptics and Dendritic Spine Editing

Esta tesis se ha desarrollado en el contexto del proyecto Cajal Blue Brain, una iniciativa europea dedicada al estudio del cerebro. Uno de los objetivos de esta iniciativa es desarrollar nuevos métodos y nuevas tecnologías que simplifiquen el análisis de datos en el campo neurocientífico. El presente trabajo se ha centrado en diseñar herramientas que combinen información proveniente de distintos canales sensoriales con el fin de acelerar la interacción y análisis de imágenes neurocientíficas. En concreto se estudiará la posibilidad de combinar información visual con información háptica. Las espinas dendríticas son pequeñas protuberancias que recubren la superficie dendrítica de muchas neuronas del cerebro. A día de hoy, se cree que tienen un papel clave en la transmisión de señales neuronales. Motivo por el cual, el interés por parte de la comunidad científica por estas estructuras ha ido en aumento a medida que las técnicas de adquisición de imágenes mejoraban hasta alcanzar una calidad suficiente para analizar dichas estructuras. A menudo, los neurocientíficos utilizan técnicas de microscopía con luz para obtener los datos que les permitan analizar estructuras neuronales tales como neuronas, dendritas y espinas dendríticas. A pesar de que estas técnicas ofrezcan ciertas ventajas frente a su equivalente electrónico, las técnicas basadas en luz permiten una menor resolución. En particular, estructuras pequeñas como las espinas dendríticas pueden capturarse de forma incorrecta en las imágenes obtenidas, impidiendo su análisis. En este trabajo, se presenta una nueva técnica, que permite editar imágenes volumétricas, mediante un dispositivo háptico, con el fin de reconstruir de los cuellos de las espinas dendríticas. Con este objetivo, en un primer momento se desarrolló un algoritmo que proporciona retroalimentación háptica en datos volumétricos, completando la información que provine del canal visual. Dicho algoritmo de renderizado háptico permite a los usuarios tocar y percibir una isosuperficie en el volumen de datos. El algoritmo asegura un renderizado robusto y eficiente. Se utiliza un método basado en las técnicas de “marching tetrahedra” para la extracción local de una isosuperficie continua, lineal y definida por intervalos. La robustez deriva tanto de una etapa de detección de colisiones continua de la isosuperficie extraída, como del uso de técnicas eficientes de renderizado basadas en un proxy puntual. El método de “marching tetrahedra” propuesto garantiza que la topología de la isosuperficie extraída coincida con la topología de una isosuperficie equivalente determinada utilizando una interpolación trilineal. Además, con el objetivo de mejorar la coherencia entre la información háptica y la información visual, el algoritmo de renderizado háptico calcula un segundo proxy en la isosuperficie pintada en la pantalla. En este trabajo se demuestra experimentalmente las mejoras en, primero, la etapa de extracción de isosuperficie, segundo, la robustez a la hora de mantener el proxy en la isosuperficie deseada y finalmente la eficiencia del algoritmo. En segundo lugar, a partir del algoritmo de renderizado háptico propuesto, se desarrolló un procedimiento, en cuatro etapas, para la reconstrucción de espinas dendríticas. Este procedimiento, se puede integrar en los cauces de segmentación automática y semiautomática existentes como una etapa de pre-proceso previa. El procedimiento está diseñando para que tanto la navegación como el proceso de edición en sí mismo estén controlados utilizando un dispositivo háptico. Se han diseñado dos experimentos para evaluar esta técnica. El primero evalúa la aportación de la retroalimentación háptica y el segundo se centra en evaluar la idoneidad del uso de un háptico como dispositivo de entrada. En ambos casos, los resultados demuestran que nuestro procedimiento mejora la precisión de la reconstrucción. En este trabajo se describen también dos casos de uso de nuestro procedimiento en el ámbito de la neurociencia: el primero aplicado a neuronas situadas en la corteza cerebral humana y el segundo aplicado a espinas dendríticas situadas a lo largo de neuronas piramidales de la corteza del cerebro de una rata. Por último, presentamos el programa, Neuro Haptic Editor, desarrollado a lo largo de esta tesis junto con los diferentes algoritmos ya mencionados. ABSTRACT This thesis took place within the Cajal Blue Brain project, a European initiative dedicated to the study of the brain. One of the main goals of this project is the development of new methods and technologies simplifying data analysis in neuroscience. This thesis focused on the development of tools combining information originating from distinct sensory channels with the aim of accelerating both the interaction with neuroscience images and their analysis. In concrete terms, the objective is to study the possibility of combining visual information with haptic information. Dendritic spines are thin protrusions that cover the dendritic surface of numerous neurons in the brain and whose function seems to play a key role in neural circuits. The interest of the neuroscience community toward those structures kept increasing as and when acquisition methods improved, eventually to the point that the produced datasets enabled their analysis. Quite often, neuroscientists use light microscopy techniques to produce the dataset that will allow them to analyse neuronal structures such as neurons, dendrites and dendritic spines. While offering some advantages compared to their electronic counterpart, light microscopy techniques achieve lower resolutions. Particularly, small structures such as dendritic spines might suffer from a very low level of fluorescence in the final dataset, preventing further analysis. This thesis introduces a new technique enabling the edition of volumetric datasets in order to recreate dendritic spine necks using a haptic device. In order to fulfil this objective, we first presented an algorithm to provide haptic feedback directly from volumetric datasets, as an aid to regular visualization. The haptic rendering algorithm lets users perceive isosurfaces in volumetric datasets, and it relies on several design features that ensure a robust and efficient rendering. A marching tetrahedra approach enables the dynamic extraction of a piecewise linear continuous isosurface. Robustness is derived using a Continuous Collision Detection step coupled with acknowledged proxy-based rendering methods over the extracted isosurface. The introduced marching tetrahedra approach guarantees that the extracted isosurface will match the topology of an equivalent isosurface computed using trilinear interpolation. The proposed haptic rendering algorithm improves the coherence between haptic and visual cues computing a second proxy on the isosurface displayed on screen. Three experiments demonstrate the improvements on the isosurface extraction stage as well as the robustness and the efficiency of the complete algorithm. We then introduce our four-steps procedure for the complete reconstruction of dendritic spines. Based on our haptic rendering algorithm, this procedure is intended to work as an image processing stage before the automatic segmentation step giving the final representation of the dendritic spines. The procedure is designed to allow both the navigation and the volume image editing to be carried out using a haptic device. We evaluated our procedure through two experiments. The first experiment concerns the benefits of the force feedback and the second checks the suitability of the use of a haptic device as input. In both cases, the results shows that the procedure improves the editing accuracy. We also report two concrete cases where our procedure was employed in the neuroscience field, the first one concerning dendritic spines in the human cortex, the second one referring to an ongoing experiment studying dendritic spines along dendrites of mouse cortical pyramidal neurons. Finally, we present the software program, Neuro Haptic Editor, that was built along the development of the different algorithms implemented during this thesis, and used by neuroscientists to use our procedure.

Developmental regulation of spine motility in the mammalian central nervous system

The function of dendritic spines, postsynaptic sites of excitatory input in the mammalian central nervous system (CNS), is still not well understood. Although changes in spine morphology may mediate synaptic plasticity, the extent of basal spine motility and its regulation and function remains controversial. We investigated spine motility in three principal neurons of the mouse CNS: cerebellar Purkinje cells, and cortical and hippocampal pyramidal neurons. Motility was assayed with time-lapse imaging by using two-photon microscopy of green fluorescent protein-labeled neurons in acute and cultured slices. In all three cell types, dendritic protrusions (filopodia and spines) were highly dynamic, exhibiting a diversity of morphological rearrangements over short (<1-min) time courses. The incidence of spine motility declined during postnatal maturation, but dynamic changes were still apparent in many spines in late-postnatal neurons. Although blockade or induction of neuronal activity did not affect spine motility, disruption of actin polymerization did. We hypothesize that this basal motility of dendritic protrusions is intrinsic to the neuron and underlies the heightened plasticity found in developing CNS.

Down-regulation of dendritic spine and glutamic acid decarboxylase 67 expressions in the reelin haploinsufficient heterozygous reeler mouse

Heterozygous reeler mice (HRM) haploinsufficient for reelin express ≈50% of the brain reelin content of wild-type mice, but are phenotypically different from both wild-type mice and homozygous reeler mice. They exhibit, (i) a down-regulation of glutamic acid decarboxylase 67 (GAD67)-positive neurons in some but not every cortical layer of frontoparietal cortex (FPC), (ii) an increase of neuronal packing density and a decrease of cortical thickness because of neuropil hypoplasia, (iii) a decrease of dendritic spine expression density on basal and apical dendritic branches of motor FPC layer III pyramidal neurons, and (iv) a similar decrease in dendritic spines expressed on the basal dendrite branches of CA1 pyramidal neurons of the hippocampus. To establish whether the defect of GAD67 down-regulation observed in HRM is responsible for neuropil hypoplasia and decreased dendritic spine density, we studied heterozygous GAD67 knockout mice (HG67M). These mice exhibited a down-regulation of GAD67 mRNA expression in FPC (about 50%), but they expressed normal amounts of reelin and had no neuropil hypoplasia or down-regulation of dendritic spine expression. These findings, coupled with electron-microscopic observations that reelin colocalizes with integrin receptors on dendritic spines, suggest that reelin may be a factor in the dynamic expression of cortical dendritic spines perhaps by promoting integrin receptor clustering. These findings are interesting because the brain neurochemical and neuroanatomical phenotypic traits exhibited by the HRM are in several ways similar to those found in postmortem brains of psychotic patients.

Fiori e spine : pensieri /

Mode of access: Internet.

Spondylotherapy; physio-therapy of the spine based on a study of clinical physiology,

Mode of access: Internet.

Magnetic resonance imaging analysis of the upper cervical spine extensor musculature in an asymptomatic cohort: an index of fat within muscle

AIM: To establish a simple method to quantify muscle/fat constituents in cervical muscles of asymptomatic women using magnetic resonance imaging (MRI), and to determine whether there is an age effect within a defined age range. MATERIALS AND METHODS: MRI of the upper cervical spine was performed for 42 asymptomatic women aged 18-45 years. The muscle and fat signal intensities on axial spin echo T1-weighted images were quantitatively classified by taking a ratio of the pixel intensity profiles of muscle against those of intermuscular fat for the rectus capitis posterior major and minor and inferior obliquus capitis muscles bilaterally. Inter- and intra-examiner agreement was scrutinized. RESULTS: The average relative values of fat within the upper cervical musculature compared with intermuscular fat indicated that there were only slight variations in indices between the three sets of muscles. There was no significant correlation between age and fat indices. There were significant differences for the relative fat within the muscle compared with intermuscular fat and body mass index for the right rectus capitis posterior major and right and left inferior obliquus capitis muscles (p = 0.032). Intraclass correlation coefficients for intraobserver agreement ranged from 0.94 to 0.98. Inter-rater agreement of the measurements ranged from 0.75 to 0.97. CONCLUSION: A quantitative measure of muscle/fat constituents has been developed, and results of this study indicate that relative fatty infiltration is not a feature of age in the upper cervical extensor muscles of women aged 18-45 years. (C) 2005 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Intra-abdominal pressure increases stiffness of the lumbar spine

Intra-abdominal pressure (IAP) increases during many tasks and has been argued to increase stability and stiffness of the spine. Although several studies have shown a relationship between the IAP increase and spinal stability, it has been impossible to determine whether this augmentation of mechanical support for the spine is due to the increase in IAP or the abdominal muscle activity which contributes to it. The present study determined whether spinal stiffness increased when IAP increased without concurrent activity of the abdominal and back extensor muscles. A sustained increase in IAP was evoked by tetanic stimulation of the phrenic nerves either. unilaterally or bilaterally at 20 Hz (for 5 s) via percutaneous electrodes in three subjects. Spinal stiffness was measured as the force required to displace an indentor over the L4 or L2 spinous process with the subjects lying prone. Stiffness was measured as the slope of the regression line fitted to the linear region of the force-displacement curve. Tetanic stimulation of the diaphragm increased IAP by 27-61% of a maximal voluntary pressure increase and increased the stiffness of the spine by 8-31% of resting levels. The increase in spinal stiffness was positively correlated with the size of the IAP increase. IAP increased stiffness at L2 and L4 level. The results of this:study provide evidence that the stiffness of the lumbar spine is increased when IAP is elevated. (C) 2004 Elsevier Ltd. All rights reserved.

Regional morphology of the transversus abdominis and obliquus internus and externus abdominis muscles

Background. The mechanisms by which the abdominal muscles move and control the lumbosacral spine are not clearly understood. Descriptions of abdominal morphology are also conflicting and the regional anatomy of these muscles has not been comprehensively examined. The aim of this study was to investigate the morphology of regions of transversus abdominis and obliquus internus and externus abdominis. Methods. Anterior and posterolateral abdominal walls were dissected bilaterally in 26 embalmed human cadavers. The orientation, thickness and length of the upper, middle and lower fascicles of transversus abdominis and obliquus internus abdominis, and the upper and middle fascicles of obliquus externus abdominis were measured. Findings. Differences in fascicle orientation, thickness and length were documented between the abdominal muscles and between regions of each muscle. The fascicles of transversus abdominis were horizontal in the upper region, with increasing inferomedial orientation in the middle and lower regions. The upper and middle fascicles of obliquus internus abdominis were oriented superomedially and the lower fascicles inferomedially. The mean vertical dimension of transversus abdominis that attaches to the lumbar spine via the thoracolumbar fascia was 5.2 (SD 2.1) cm. Intramuscular septa were observed between regions of transversus abdominis, and obliquus internus abdominis could be separated into two distinct layers in the lower and middle regions. Interpretation. This study provides quantitative data of morphological differences between regions of the abdominal muscles, which suggest variation in function between muscle regions. Precise understanding of abdominal muscle anatomy is required for incorporation of these muscles into biomechanical models. Furthermore, regional variation in their morphology may reflect differences in function. (C) 2004 Elsevier Ltd. All rights reserved.

Variability in Cobb angle measurements using reformatted computerized tomography scans

Study Design. Survey of intraobserver and interobserver measurement variability. Objective. To assess the use of reformatted computerized tomography (CT) images for manual measurement of coronal Cobb angles in idiopathic scoliosis. Summary of Background Data. Cobb angle measurements in idiopathic scoliosis are traditionally made from standing radiographs, whereas CT is often used for assessment of vertebral rotation. Correlating Cobb angles from standing radiographs with vertebral rotations from supine CT is problematic because the geometry of the spine changes significantly from standing to supine positions, and 2 different imaging methods are involved. Methods. We assessed the use of reformatted thoracolumbar CT images for Cobb angle measurement. Preoperative CT of 12 patients with idiopathic scoliosis were used to generate reformatted coronal images. Five observers measured coronal Cobb angles on 3 occasions from each of the images. Intraobserver and interobserver variability associated with Cobb measurement from reformatted CT scans was assessed and compared with previous studies of measurement variability using plain radiographs. Results. For major curves, 95% confidence intervals for intraobserver and interobserver variability were +/- 6.6 degrees and +/- 7.7 degrees, respectively. For minor curves, the intervals were +/- 7.5 degrees and +/- 8.2 degrees, respectively. Intraobserver and interobserver technical error of measurement was 2.4 degrees and 2.7 degrees, with reliability coefficients of 88% and 84%, respectively. There was no correlation between measurement variability and curve severity. Conclusions. Reformatted CT images may be used for manual measurement of coronal Cobb angles in idiopathic scoliosis with similar variability to manual measurement of plain radiographs.