Diffusion MRI of Brain Tissue: Importance of Axonal Trajectory

Obtaining microstructural information non-invasively on brain tissue remains a challenge. Diffusion magnetic resonance imaging (dMRI) is an imaging method that can provide such information. That includes geometrical considerations of nerve cells projections, axons, that are present in the white matter of the human brain. Axons carry information encoded into electrical impulses to other cells. The thesis deals with estimating parameters of the axonal trajectories, modeled as one-dimensional pathways, from the dMRI signal. That is achieved in two steps: constructing a forward model to predict the dMRI signal and, vice versa, estimating the tissue parameters from dMRI signal by solving the so-called inverse problem. The proposed forward model employs a spectral analysis of dMRI signal. This formulation enables signal prediction for any gradient waveform and helps to identify the physical characteristics of the underlying system that are preserved in the dMRI signal. The physical properties are represented in so-called diffusion spectra whereas gradient waveforms, that sensitizes the signal, are in the encoding spectra. To mimic biologically plausible axonal trajectories, axonal trajectories were modeled by a 1D-toy model that incorporates harmonic waves with variable degree of randomness. Different numerical methods for computation of diffusion spectra were compared, and the resulting spectra were characterized by a phenomenological model incorporating three parameters. It was not possible to estimate the exact parameters of the 1D-toy model from diffusion spectra. Nonetheless, it was possible to estimate their statistical descriptors, namely microscopic orientation dispersion and dispersion-weighted wavelength. Solving the inverse problem posed a major challenge. The phenomenological model of the diffusion spectra was incorporated in a forward model of the diffusion-weighted signal perpendicular to the trajectory and applied to a state-of-the-art data acquired in human brain white matter of a healthy volunteer. It was not possible to estimate all the parameters of the phenomenological model but by constraining the parameters to plausible values we could estimate the last that was within the range predicted by histology. Incorporating trajectory-parameters in the model of white matter diffusion yielded fit residuals as small as those obtained with current state-of-the-art models assuming parallel, straight, and cylindrical cylinders. However, the cylinder model predicted axon diameters far outside the range expected from histology. We conclude that neglecting the axonal trajectories leads to biased models of axons in brain white matter.MRI can serve as an example of successfully applied fundamental research from physics to biological sciences, humanities, chemistry or medicine. Biomolecules in biochemistry can be probed with atomic resolution. Nanomaterials in material sciences, porous rocks in geology, cell structures or tissues in biology and medicine can be examined. Statistical analysis of MRI signal can reveal functional state of the brain and is relevant in e.g. psychology. This thesis deals mainly with applications within medical sciences. Diffusion magnetic resonance imaging (dMRI) unravels the tissue microstructure, i.e. the structure of tissue on the micrometer length scale. At this scale, the arrangement of cells and other biologically relevant structures emerges as a new property from a deeper, biochemical, scale. Microstructural appearance is often defining feature of biological tissues and is intertwined with their biological behavior, which is a highly interesting information from a medical point of view. In this project, we study in a systematic way, often neglected, geometrical aspects of axons called axonal trajectories. Axons are the wiring of the brain. Based on microscopical images we proposed their representation, inspected their properties and forecasted the outcome of a diffusion measurement. The inverse question, whether the information on the axonal trajectories can be inferred from the outcome of measurement, and whether they could be neglected, was answered as well. The results suggest that non-straight axonal trajectories need to be considered in the of representations of axons, although to estimate them reliably the practical diffusion measurements need to be improved. The estimated properties of axonal trajectories were congruent to the gold-standard method, microscopy. Same methodology applied to the investigation of axonal trajectories can be employed in other problems in the dMRI field and may also lead to better understanding of the nature of the results of the diffusion measurements in the human tissue. Potentially, novel biomarkers that could help to diagnose diseases could be discovered. Generally, dMRI is an interesting research field where potential breakthrough could be made. It probes the microstructural region that is highly important from the biological point of view, has a solid foundation in physical theory, allows for large variety of possible arrangements of the dMRI experiments and is not as widespread as other imaging modalities

Roadmap on semiconductor-cell biointerfaces.

This roadmap outlines the role semiconductor-based materials play in understanding the complex biophysical dynamics at multiple length scales, as well as the design and implementation of next-generation electronic, optoelectronic, and mechanical devices for biointerfaces. The roadmap emphasizes the advantages of semiconductor building blocks in interfacing, monitoring, and manipulating the activity of biological components, and discusses the possibility of using active semiconductor-cell interfaces for discovering new signaling processes in the biological world

An instinct for detection: psychological perspectives on CCTV surveillance

The aim of this article is to inform and stimulate a proactive, multidisciplinary approach to research and development in surveillance-based detective work. In this article we review some of the key psychological issues and phenomena that practitioners should be aware of. We look at how human performance can be explained with reference to our biological and evolutionary legacy. We show how critical viewing conditions can be in determining whether observers detect or overlook criminal activity in video material. We examine situations where performance can be surprisingly poor, and cover situations where, even once confronted with evidence of these detection deficits, observers still underestimate their susceptibility to them. Finally we explain why the emergence of these relatively recent research themes presents an opportunity for police and law enforcement agencies to set a new, multidisciplinary research agenda focused on relevant and pressing issues of national and international importance

Consciousness and vision in man : where philosophy has gone wrong

My central claim is that philosophers of mind have failed to take adequate account of empirical evidence regarding human consciousness and vision. Experiments on split-brain patients over the past fifty years reveal consciousness in both cerebral hemispheres. I claim specifically that (a) consciousness in the right hemisphere is inherited from our animal ancestors; (b) consciousness in the left hemisphere arose during human evolution in association with language; and (c) the existence of both forms of consciousness provides the best explanation for many aspects of normal human experience. Evidence for two cortical visual pathways in the human brain has been expanding for twenty years. The ventral pathway is specialised for object identification, and the dorsal pathway for the control of actions in respect of those objects. The evidence has been challenged by those who have failed (a) to distinguish between the visual pathways themselves and processes served by the pathways, and (b) to recognise the specific circumstances in which actions draw on one pathway. I claim that in the left hemisphere only the ventral pathway reaches consciousness. The combination of two visual pathways with two centres of consciousness challenges traditional views about perception. I claim that (a) perception is distinct from seeing; (b) perception is limited to the left hemisphere; and (c) the parallel process in the right hemisphere is associated with the emotions. The presence of two centres of consciousness challenges traditional views on the unity of consciousness and on personhood; but it also offers an explanation for conflicting views on the emotions and the existence of self-deception. I distinguish my claims about human consciousness from the Dual Systems (or Two Minds) Theory. Although there are superficial parallels, the latter theory denies that both systems/minds are conscious, and takes no account of the specialisation of the cerebral hemispheres revealed by experiments on split-brain patients. I conclude that philosophy must incorporate empirical evidence if it is to avoid claims of irrelevance

3D reconstruction of motor pathways from tract tracing rhesus monkey

Magnetic resonance imaging (MRI) has transformed the world of non-invasive imaging for diagnostic purposes. Modern techniques such as diffusion weighted imaging (DWI), diffusion tensor imaging (DTI), and diffusion spectrum imaging (DSI) have been used to reconstruct fiber pathways of the brain - providing a graphical picture of the so-called "connectome." However, there exists controversy in the literature as to the accuracy of the diffusion tractography reconstruction. Although various attempts at histological validation been attempted, there is still no 3D histological pathway validation of the fiber bundle trajectories seen in diffusion MRI. Such a validation is necessary in order to show the viability of current DSI tractography techniques in the ultimate goal for clinical diagnostic application. This project developed methods to provide this 3D histological validation using the rhesus monkey motor pathway as a model system. By injecting biotinylated dextran amine (BDA) tract tracer into the hand area of primary motor cortex, brain section images were reconstructed to create 3D fiber pathways labeled at the axonal level. Using serial coronal brain sections, the BDA label was digitized with a high resolution digital camera to create image montages of the fiber pathway with individual sections spaced at 1200 micron intervals through the brain. An MRI analysis system, OSIRX, was then used to reconstruct these sections into a 3D volume. This is an important technical step toward merging the BDA fiber tract histology with diffusion MRI tractography of the same brain, enabling identification of the valid and inaccurate aspects of diffusion fiber reconstruction. This will ultimately facilitate the use of diffusion MRI to quantify tractography, non-invasively and in vivo, in the human brain

Graph analysis of functional brain networks: practical issues in translational neuroscience

The brain can be regarded as a network: a connected system where nodes, or units, represent different specialized regions and links, or connections, represent communication pathways. From a functional perspective communication is coded by temporal dependence between the activities of different brain areas. In the last decade, the abstract representation of the brain as a graph has allowed to visualize functional brain networks and describe their non-trivial topological properties in a compact and objective way. Nowadays, the use of graph analysis in translational neuroscience has become essential to quantify brain dysfunctions in terms of aberrant reconfiguration of functional brain networks. Despite its evident impact, graph analysis of functional brain networks is not a simple toolbox that can be blindly applied to brain signals. On the one hand, it requires a know-how of all the methodological steps of the processing pipeline that manipulates the input brain signals and extract the functional network properties. On the other hand, a knowledge of the neural phenomenon under study is required to perform physiological-relevant analysis. The aim of this review is to provide practical indications to make sense of brain network analysis and contrast counterproductive attitudes

Child cortisol moderates the association between family routines and emotion regulation in lowâ income children

Biological and social influences both shape emotion regulation. In 380 lowâ income children, we tested whether biological stress profile (cortisol) moderated the association among positive and negative home environment factors (routines; chaos) and emotion regulation (negative lability; positive regulation). Children (M ageâ =â 50.6, SDâ =â 6.4 months) provided saliva samples to assess diurnal cortisol parameters across 3 days. Parents reported on home environment and child emotion regulation. Structural equation modeling was used to test whether cortisol parameters moderated associations between home environment and child emotion regulation. Results showed that home chaos was negatively associated with emotion regulation outcomes; cortisol did not moderate the association. Child cortisol level moderated the routinesâ emotion regulation association such that lack of routine was most strongly associated with poor emotion regulation among children with lower cortisol output. Findings suggest that underlying child stress biology may shape response to environmental influences.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135499/1/dev21471_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135499/2/dev21471.pd

Hydrocephalus 2008, 17–20th September, Hannover Germany: a conference report

Hydrocephalus 2008 was held 17–20 September in Hannover, Germany, at the invitation of Petra M Klinge (President), co-hosted by Joachim K. Krauss (Vice President), and Madjid Samii (Honorary President). This meeting was a successor to Hydrocephalus 2006 held in Göteborg, Sweden, organised by Past-President, Carsten Wikkelso. The conference began with a general introductory session of six talks including three invited lectures, followed by eighteen parallel sessions. Subjects covered were hydrocephalus signs, symptoms and diagnosis, especially in normal pressure hydrocephalus; cerebrospinal fluid (CSF) physics and dynamics; CSF function and modelling of function; dementia and quality of life, economy, health care and rehabilitation; neuropsychology, cognition and outcome assessment; neuroimaging, functional imaging and non-invasive diagnostics; paediatric and adolescent hydrocephalus; intelligent shunt and valve design (e.g. telemetry, adjustable and antimicrobial shunts); endoscopic third ventriculostomy; technical advances and image-guided surgical approaches in the treatment of hydrocephalus; brain metabolism, biomarkers and biophysics; co-morbidity, classification and aetiology; epidemiology, registries and clinical trials; experimental hydrocephalus; and pharmaceutical modulation of central nervous system function (CNS drug delivery). Each session began with introductory talks from the invited chairpersons followed by six to eight submitted oral presentations. Overall, 136 oral presentations and 18 posters were presented, the abstracts of which were published elsewhere [1]. We present here an account of the introductory session, the invited chairperson's talks and the concluding remarks by Anthony Marmarou