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    Multi-modal Investigation of Cortical Connectivity at Multiple Scales

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    La risonanza magnetica (RM) riveste una grande e crescente importanza nel campo del neuroimaging. Tra le modalità piu interessanti si colloca la RM pesata in diffusione (dMRI) che, insieme alla RM funzionale, alla magneto-encefalografia (MEG), ell'elettro-encefalografia (EEG) e alla spettroscopia funzionale nel vicino infrarosso (fNIRS) contribuisce a costituire una notevole e differenziata mole di informazioni che consentono di analizzare e modellare la struttura e la funzione cerebrale. La dMRI presenta il grande vantaggio di quantificare la diffusività tissutale in modo non invasivo attraverso la misura dei micromovimenti delle molecole di acqua, consentendo non solo di caratterizzare la struttura della materia bianca con elevata risoluzione, ma anche di supportare le attività cliniche sia quale supporto alla diagnostica sia quale strumento di pianificazione prechirurgica. Allo stato dell'arte, numerosi aspetti richiedono restano da chiarire determinando un notevole impiego di risorse a livello di ricerca. Tra i principali sono la riproducibità delle misure, la ricostruzione della funzione di distribuzione delle orientazioni (orientation diffusion function, ODF), specialmente in presenza di rumore, la modellazione dei network strutturale e funzionale e lo studio delle rispettive interazioni. In questa tesi, alcuni di questi aspetti sono stati analizzati e sono state proposte alcune soluzioni a livello sia metodologico che clinico. In particolare, a partire da dati diffusion spectrum imaging (DSI), è stato proposto un metodo di denoising del segnale basato sulla multirisoluzione che ha consentito la ricostruzione piu precisa della ODF e quindi della trattografia, è stato sviluppato un metodo di analisi della rimodellazione del network corticale motorio in pazienti affetti da stroke basato sulla tract-based quantification di parametri estratti dalla dMRI e dalla RM a trasferimento di magnetizzazione (MTR), ed è stato analizzato il network funzionale attivato dallo svolgimento di task motori predefiniti in vista dell'integrazione delle informazioni strutturale e funzionale in un modello corticale globale focalizzato sul loop motorio.In neuroimaging, a great interest is currently being directed to diffusion magnetic resonance imaging (dMRI) which, in addition to functional magnetic resonance imaging (fMRI), magnetoencephalography (MEG), electroencephalography (EEG), functional near-infrared-spectroscopy (fNIRS) provides a large spectrum of measurements to enlighten the brain structure and function. The success of dMRI is deeply rooted in the powerful concept that during their random, diffusion-driven displacements molecules probe tissue structure at a microscopic scale well beyond the usual image resolution. Diffusion imaging opens several perspectives for what concerns the development of new non invasive techniques not only to optimize the diagnosis and therapy planning for oncological patients but also to discover the anatomical structure of the human cortex.Though, many issues still remains to be solved. Among the most striking are the reconstruction of the ODF (orientation distribution function) in noisy conditions, its reproducibility over time points acquisitions, the intra and inter-subject registration and the integration of functional information about the cortical activity within the reconstruction of the fiber network from raw data. This is of paramount importance as it would allow to link the functional information to the structural anatomical substrate. This thesis aims at investigating a subset of such issues in order to trace the path to the overall solution. In particular, it aims at integrating multiscale space-scale processing, diffusion imaging and cortical signals to (i) improve the orientation diffusion function (ODF) reconstruction, reproducibility and robustness to noise; (ii) contribute new methods for the registration of intra and inter-modality multidimensional data (tensors, probability distributions); (iii) explore the possibility of integrating functional signals in the processing pipeline in order to guide the fiber reconstruction and as a potential mean of validation of the proposed methods.From the clinical point of view, the goal of this thesis is to make tractography exploitable in daily practice for surgical planning and follow-up, assessment of degenerative pathologies as well as of pharmacological treatments

    Multiscale representations for ODF denoising in diffusion spectrum imaging

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    The established methods for today's clinical applications include the use of the diffusion Magnetic Resonance Imaging (dMRI). The proposed work concerns wavelet-based denoising of the Diffusion Spectrum Imaging (DSI) data. Both simulated data and real brain data are considered. Diffusion data are first reconstructed by inverse Fourier transform and then projected to the multiscale domain by 3D wavelet transform. The 3D extensions of both critically sampled (Discrete Wavelet Transformation, DWT) and overcomplete representations (Stationary Wavelet Transformation, SWT) have been considered and applied to the 3D reconstructed diffusion propagator. Then, denoising has been performed by (soft/hard) thresholding. The two-fiber crossing case has been considered for both the synthetic DSI data and real data. Simulation data for fiber crossings with different fiber-crossing angles (45, 60, 90 degree), Rician-noise SNR (10, 15, 20, 30, 50, 100 db) using 514-point grid sampling scheme and the maximum b-value of 6000 s/mm-square were generated. Simulations were repeated 100 times. The Kullback-LeiblerDivergence (KLD) has been used to evaluate the performance of the denoising algorithm after signal recovery. Real data were acquired on a healthy volunteer using a 3T scanner (TIM Trio, Siemens, Erlangen, Germany). The maximum b-value was 8000 s/mm-square with 514 diffusion directions. In this case, the KLD was used to quantify the difference between the two reconstruction strategies since the ground truth was not available. Visual inspection confirmed that SWT providesbetter ODF (Orientation Distribution Function) recovery with respect to DWT. Overall, results show that the SWT algorithm provides a more reliable reconstruction of the ODF with respect to the DWT and improves DSI data denoising in sparse domains. Ongoing work includes the assessment of the improvement in terms of angular resolution

    Tract-based quantitative analysis of myelin and axonal remodeling in the uninjured motor network after stroke

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    Previous works from our group showed axonal and myelin plasticity in the uninjured motor network of stroke patients with motor deficits [1-2].However, these studies focused on average MRI indexes of tract integrity namely generalized fractional anisotropy (GFA) [3] for axonal properties andmagnetization transfer ratio (MTR) [4] for myelin characteristics. These approaches offered a global view of tract remodeling but failed in revealing subtlechanges affecting only partially single motor connections. Depending on the location and extension of the stroke lesion, in fact, parts of connections mightbe more susceptible than other to plastic changes over time. In this study, we performed track-based quantitative analysis for assessing GFA and MTRvalues along the tract and characterizing their variations at large- and small-scale

    Does It Exist a Link between Performance and Parietal Cortex Activity in Surgical Tasks?

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    This pilot study would to explore the ideas of a possible correlation between the goodness of surgical performance in robotic assisted minimally invasive surgery (MIS) and posterior parietal cortex (PPC) activity. This cortical area is known to be involved in stereoscopic vision (Sakata et al., 1997), visual control of eye movements and hand-eye co-ordination (Shikata et al., 1996). This issue is of great interest because robotic assisted surgery provides the surgeon with a stereoscopic view of the operative field combined with aligned motor-visual axes and mechatronically controlled instruments. In this contribution, we conduct an exploratory experiment aiming at investigating the hypothesis of a correlation between the performance in reached in a surgically relevant task and the activation of PPC channels as revealed by the fNIRS measurements. First results are very promising and suggest the occurrence of a link between performance and channel activation

    Tract-based assessment of the subcortical motor network plasticity after stroke

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    We previously established that uninjured cortical motor network is remodeling in stroke patients with motor deficits [1.2]. Both axonal [1] andmyelin plasticity [2] were, in fact, observed during 6 months longitudinal follow-up. However, the contribution of uninjured subcortical motor circuits in strokerecovery has not been studied yet. Therefore, in this study, we aimed at investigating myelin and axonal plasticity in the subcortical motor networks(SC-MN) contralateral to stroke by applying diffusion spectrum and magnetization transfer imaging. The SC-MS is constituted by connections between thecortical motor area, the basal ganglia and the thalamus, and it essentially consists in three major subcortical networks (figure 1): i) the sensory-motorsub-loop (primary and sensory motor areas -putamen-globus pallidus-ventral lateral thalamic nucleus-motor cortex), ii) the premotor sub-loop (premotordorsal and ventral areas (dPM, vPM)-caudate nucleus-putamen, globus pallidus-ventral anterior thalamic nuleus-premotor cortex iii) the supplementarymotor area (SMA) sub-loop (SMA - putamen and caudatus - globus pallidus-ventral anterior and the ventro-lateral thalamic nuclei-SMA)

    Myelin plasticity does not significantly influence diffusion remodelling in the uninjured motor network after stroke

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    Connectivity plasticity in the uninjured hemisphere after stroke has been reported in a number of experimental [1,2] and human [3-5]studies. Recently, we used Diffusion Spectrum Imaging (DSI) to explore longitudinal changes in the contra-lateral motor network of patients who sufferedfrom stroke [6] and we showed that contra-lateral motor tracts changes in Generalized Fractional Anisotropy (GFA) correlated strongly with clinicalscores. Furthermore, GFA measured in the acute phase together with a routine motor score and age proved to be strong predictors of motor outcome atsix months (r2=0.96, p=0.0002) [6]. Whether the observed changes in GFA are due to axonal remodeling or myelin plasticity remains however an openissue. GFA is the standard deviation of the diffusion process along different diffusion directions, representing fibre trajectories in tractographyreconstructions [7]. Like Fractional Anisotropy, GFA can be influenced by axonal integrity and, to a lesser extent, by the properties of intra-axonaltransport and myelin [8]. In this context, we wanted to study the behaviour of the Magnetisation Transfer Ratio (MTR) in the contra-lateral motor networkand to correlate it to the longitudinal changes in GFA [6]. The MTR is a semi-quantitative parameter which increases with the content of myelin and thedecreasing of water content along axonal fibers

    A diffusion spectrum imaging study of the cortico-subcortical motor connections after stroke

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    Connectivity plasticity in the uninjured hemisphere after stroke has been reported in a number of experimental [1-2] and human [3-5] studies. Recently, we used Diffusion Spectrum Imaging (DSI) to explore longitudinal changes in the contra-lateral motor network of patients, who suffered from stroke and had good functional recovery [6]. In this study, we showed a broad spectrum of changes in Generalized Fractional Anisotropy (GFA) in connections between primary and secondary motor areas contralateral to the injured hemisphere [6]. Furthermore, GFA measured in the acute phase together with a routine motor score and age proved to be strong predictors of motor outcome at six months (r2=0.96, p=0.0002) [6]. In the current work, we aimed at investigating the presence of remodelling of the cortico-subcortical motor system (CS-MS) in the same cohort of stroke patients. The CS-MS is constituted by connections between the cortical motor area and the basal ganglia and the thalamus and is essentially constituted by three major subcortical network (figure 1A): i) the sensory-motor sub-loop (primary and sensory motor areas, - putamen-globus pallidus - ventral lateral thalamic nucleus-motor cortex), ii) the premotor sub-loop ( premotor dorsal and ventral areas (dPM, vPM)-caudate nucleus - putamen, -globus pallidus - - ventral anterior thalamic nuleus-premotor cortex iii) the supplementary motor area (SMA) sub-loop (SMA - putamen and caudate- globus pallidus -ventral anterior and the ventro-lateral thalamic nuclei-SMA)

    Quantitative analysis of myelin and axonal remodeling in the uninjured motor network after stroke

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    Objectives: Contralesional brain connectivity plasticity was previously reported after stroke. This study aims at disentangling the biological mechanisms underlying connectivity plasticity in the uninjured motor network after an ischemic lesion. In particular, we measured generalized fractional anisotropy (GFA) and magnetization transfer ratio (MTR) to assess whether post-stroke connectivity remodeling depend on axonal and/or myelin changes. Materials and Methods: Diffusion Spectrum Imaging (DSI) and Magnetization Transfer MRI at 3T were performed in 10 patients in acute phase, at one and six months after stroke, which was affecting motor cortical and/or subcortical areas. Ten age- and gender- matched healthy volunteers were scanned one month apart for longitudinal comparison. Clinical assessment was also performed in patients prior to MRI. In the contra-lesional hemisphere, average measures and tract-based quantitative analysis of GFA and MTR was performed to assess axonal integrity and myelination along motor connections as well as their variations in time. Results and Conclusions: Mean and tract-based measures of MTR and GFA showed significant changes in a number of contralesional motor connections, confirming both axonal and myelin plasticity in our cohort of patients. Moreover, density-derived features (peak height, standard deviation-SD and skewness) of GFA and MTR along the tracts showed additional correlation with clinical scores than mean values. These findings reveal the interplay between contralateral myelin and axonal remodeling after stroke

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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