Research program
TEBAM: study, development and physiological-clinical validation of a multi-modal methodology for the 3D "True Electrical Brain Activity Mapping" in normal and pathological subjects
University Co-ordinator
Università degli Studi di TRIESTE -
ELETTROTECNICA, ELETTRONICA ED INFORMATICA - TRIESTE(TS)
Research Unit Leader
Paolo INCHINGOLO
Description
Research objectives------------------------There are several critical situations in which the techniques of brain electrical activity reconstruction normally used may be inadequate, as in the presence of pathologies (expansive morphological lesions altering functionally and anatomically the encephalon) and/or the activation of deep brain or temporal cortical areas, possible locations of epileptic focuses.In these situations a non optimal configuration of electrodes on the scalp, that doesn't allow to collect the functional signals generated in the above mentioned critical conditions, or the introduction of too large errors in the phases of post-processing of the electroencephalographic signal due to an incorrect or incomplete modeling of the volume conductor of the head, are some of the reasons that can limit the capabilities of standard methods in the reconstruction of electrical brain activity.The Unit of Bioengineering of Trieste, which has been active for years in this field, proposes with this research project to further pursue the investigation for definition of advanced methods of reconstruction of components of electrical brain activity in the above mentioned critical conditions.This research aims to develop an investigation approach with multimodal non invasive techniques, integrating different kinds of neurophysiological and neuroimaging data, allowing localization of maximally active brain areas, both cortical and deep, and their activation sequence in a refined temporal scale.In this way it will be possible to identify the morpho-functional structures involved in the genesis and propagation of electrical brain activity and to clarify the relations they have with nearby functionally active brain areas. Methods and technologies developed will be validated in different critical conditions: pathologies (expansive morphological lesions altering functionally and anatomically the encephalon) and/or the activation of deep brain or temporal cortical areas (possible locations of epileptic focuses).Previous modeling investigations by the unit of Trieste allowed to point out the characteristics of a volume conductor head model, with reference to the electrical and geometrical characterization of possible homogeneous morphological brain lesions. Results so far were obtained from simulations mostly based upon spherical head models.For the extension of such results to realistically shaped head models, the unit of Trieste planned and realized a software for simulation and analysis of bioelectrical field problems. This software is based upon a cross-platform structure and can be run on mono or multi-processor PC with Windows or Unix O.S., and on Unix-like high performance systems (inter-university consortium CINECA).This tool solves bioelectrical problems using finite differences algorithms (FDM), allowing a flexibility in model characteristics definition higher than the one that could be obtained with any other approach, being then an essential instrument in the development of new methods of analysis and interpretation of bioelectrical phenomena.Even in front of a high computational load, there are highly qualifying and innovative points: the easiness of implementation of anisotropic structures' modeling and of gradients of conductivity variation within such structures, the easy increment or reduction of model complexity (number of compartments) and of spatial resolution of the volume conductor head model used by the numerical solvers. Such approach allows also making bioimages' segmentation procedures virtually not necessary for the construction of the volume conductor head model to be used in brain electrical activity mapping procedures, with great advantages in particular when using highly complex head models.These innovative tools of the unit of Trieste are fundamental for a realistic approach of this research proposal.Within the Coordinated Research Project, the Unit of Bioengineering of Trieste will be engaged with the definition of a volume conductor head model allowing a 3D true electrical brain activity mapping by means of its integration with electroencephalographic recordings. In particular, after having defined by means of a simulation analysis the necessary characteristics ad the possible validity limits, the Unit of Bioengineering of Trieste will be able to build a numerical 3D phantom of the head (named "volume conductor head model") mimicking the real shape of the head and of its structures with the conductivity values of its tissues, in particular in the presence of morphologic pathologies in the brain. Particular care will be devoted to the required extension for the volume conductor head model, allowing to obtain an accurate reconstruction also for deep brain sources.The research will be developed in 4 phases; of each will be now explained the partial sub-objectives:# 1) Extension of the model for the reconstruction of deep sources in the brain° 1a) The model that must be used to reconstruct deep brain sources must be extended to the lower part of the head, where there are structures like air pockets or muscles, to cite some compartments that do not have to be accounted for in the upper head analysis, that are possible compartments in the head model as they are highly anisotropic (the longitudinal conductivity of a muscle can be up to 16 times the transversal one) and/or they give rise to conductive discontinuities.From a methodological point of view we aim at simulation analysis of the required geometrical extension of the model to obtain an accurate reconstruction of deep brain sources (extending analysis to the base of the skull, or if necessary to the base of the neck). Specifically, it must be noted that bioelectrical phenomena extend to all the body conductive volume, finding in their way obstacles to the current flux (like air compartments or bone structures) but "highways" too (blood or CSF).° 1b) In the region defined in step 1a the compartments needed in the realistic head model to guarantee the required accuracy in EEG source reconstruction will be identified. In this phase also the necessity of an anisotropic description of these compartments will be evaluated.° 1c) By use of the above described realistic model, the information contained in scalp EEG recordings during activation of deep brain areas will be evaluated.EEG supplies a signal that is corrupted by artifacts and noise and is influenced by measurement electrodes positioning.The identification of noise limits in the recorded signals and the definition of a possible electrode configuration on the scalp best suited to the necessity will be performed.Both objectives will be reached by bioelectrical phenomena simulations and comparing results with those obtained by analysis of real data in collaboration with the research unit of Radiology of Trieste. As far as the studies are concerned, this Research Unit will collaborate with Research Groups with great experience in the field of the techniques for brain activity source analysis; in particular the Research Unit will take advantage of the existing collaboration with the Azienda Ospedaliera-Universitaria Triestina (Dott. Fabrizio Monti) and with the Interdepartmental BRAIN Center of the University of Trieste (Prof. Pier Paolo Battaglini).The studies on electroencephalographic data will be carried out within the Interdepartmental BRAIN Center of the University of Trieste to which this Unit belongs as "Bioengineering Unit", thanks to the cooperation of the Unit of Physiology of the Center, headed by Prof. Pier Paolo Battaglini and the Unit of Neurophysiopathology of the University Hospital of Trieste(Dott. Fabrizio Monti), which have great experience in the field of the techniques for brain activity source analysis. # 2) Contextually to the definition of the model, availability will be verified, in the field of clinical radiological exams, of information suited to such model construction.° 2a) Then a protocol will be defined for multimodal acquisition of sufficient and necessary data for model construction. In this phase, in collaboration with the Research Units of Radiology of Trieste and Pisa, volume conductor model definition will be carried out including also the individual conductivity characteristics of the tissues. Such model will be based on the quantitative deduction of electrical conductivity tensor of the tissues from water self-diffusion tensor measured by means of DT-MRI techniques. This protocol will provide both specifics for method/modality for bioimages and specifics about spatial resolution and contrast in images; it will have also to prescript possible special treatments needed for data integration. The existing collaboration with other research groups particularly specialized in the field of the experimental techniques of diffusion tensor acquisition (IRCCS Casa Sollievo della Sofferenza, S. Giovanni Rotondo - FG, Dott. Giuseppe Guglielmi) will guarantee the necessary scientific and technological knowledge.# 3) In the specific pathological context, analysis will be performed of alterations in the electrical properties of non pathological tissues due to the presence of a lesion in the encephalon. This last, in fact, occupying space, deforms and compresses the soft brain structures.° 3a) Evaluation of consequences of such morphological deformations from an electrical point of view, and of their implications from a modeling point of view.° 3b) Quantification of the effects of such local alterations in the tissues' properties on the scalp potential distribution, their interpretation and analysis of the accuracy in the reconstruction of neural sources.# 4) Development of a suite of instruments for integrated data and structures visualization, suitable to give an adequate information "feed-back" in the analysis of the results of electrical brain activity mapping, with a specific software for the visualization of the information relative to the diffusion tensor and tissue conductivity. Such instruments will be based on powerful and flexible freeware and open-source tools for graphics pipelines development, like VTK (Visualization Toolkit) and OpenGL, and will be integrated in the bioelectrical phenomena simulation system developed by the research unit.Visualizations will be based upon:° multi-monitor visualization° contemporary "multi-renderer" view on screen of different visualization modalities,+ all with "interactive navigation" (rotation and zoom)+ with synchronized perspective point of view in the different 3D windows and+ with possible different detail level choice;° stereographic low-cost 3D visualization (auto stereographic monitor allowing multi-user stereo vision or shutter glasses for single user stereography).The final goal is to conclude the research with the writing and the deposit of an Italian national and international patent.
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