Neuroimaging and Methodological research

Rosa Maria Moresco Email: methods@neuromi.it
The neuroimaging and methodological research program is an interdisciplinary program that applies imaging, computer sciences and signal analysis techniques to the study of brain functions. The program allows the access to advance technologies and instrumentation located in different institution of the Center. The methodological group is composed by neurologists, psychologists, nuclear physicians, pharmacologist, physicists, computer scientists, statisticians radio-chemists, with expertise in neuroimaging and signal analysis. The program is focused on bringing together clinicians and scientists with the common goal of studying the neurobiology of the brain in normal conditions and diseases at structural, functional and molecular levels using state of the art neuroimaging and signal processing techniques. Imaging and signal processing methodologies may be applied to different fields of neurosciences both at preclinical and clinical levels using both in vitro and in vivo approaches. Main technologies and methodological expertise available for the program are: functional and structural MRI imaging, in vivo and in vitro molecular imaging, signal processing and instrumentation development/optimization, computer sciences and statistics.
  1. Functional and structural neuroimaging allows the understanding of higher cognitive function including memory, language, reasoning, emotion, decision making and social interaction using MRI and innovative image processing and computer sciences approach (see Cognitive Neurosciences for main applications).
  2. In vivo Molecular Imaging Different translational (Positron emission tomography) or preclinical (optical imaging and Mass spectroscopy proteomic imaging) methodological approaches enable to image central or peripheral neurochemistry. Optical imaging may be used to visualize cell homing after using the gene reporter technique or selected molecular pathway using fluorescence and specific probes. As for PET based molecular imaging, main research field are focused on radiopharmacology and radiopharmaceutical development; clinical and preclinical molecular imaging applied to neuroinflammation and neurodegeneration, validation of PET tracers as potential biomarkers of therapy efficacy. The group is currently developing new radioligand that targets activation of brain immune system during nerodegeneration or neuroinflammation.
  3. MS-imaging. Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is a unique technology that explores the spatial distribution of biomolecules (proteins, peptides, lipid, drugs etc) directly in situ, thus integrating molecular information and those deriving from other imaging technologies (e.g. PET, MRI, classical stain used in histology: eosine / hematosylin, immunohistological , etc). MALDI-Imaging enables to analysed whole body, organs, tissues and cells. We are currently studying brain tissue sections, either fresh frozen or FFPE. Biomolecules with an altered expression in the different areas can be also identified by mass spectrometrometry.Figura x Neuromi_imaging Magni
  4. Molecular imaging and micro-spectroscopy. High spatial resolution with optical methods are relevant for studying the neurophysiological response in-vitro and in-vivo. Two groups at the Physics Dept. are active in this field. LABS is developing optical superresolution techniques (70 nm resolution) based on Stimulated Emission Depletion Microscopy and fluorescence correlation imaging methods to study flows in soft-matter and hemodynamics in animal models (Zebrafish and mice). Moreover two-photon microscopy (2PM) and second-harmonic generation microscopy is currently used for in-vivo deep tissue imaging. In collaboration with human physiology group at the Univ. of Pavia (prof. D’Angelo), LABS is developing optical holographic methods for the in-vivo study of connectome based on two-photon excitation of calcium or voltage sensitive dyes (1 ms/1µm time/space resolution). The group of Micro-spectroscopy at the Physics. Dept. is developing FTIR spectroscopy methods for the in-vitro study of folding and aggregation of amyloid proteins (alfa synuclein, A-beta petides, ataxin 3, prion peptides) involved in neurodegenerative diseases. By laser scanning confocal microscopy this group is also characterizing mitochondria of tumor cells under multidrug resistance, differentiating stem cells and intact organisms as transgenic C.elegans espressing A-beta peptides.
  5. Image processing and statistics. Since one is working with spatially distributed data, it is also possible to apply the inferential process to cluster spatial extension. In this case the inference focuses on topological features and instead of considering voxel-specific statistics the spatial extent of voxel clusters, considered as a single topological entities, is of interest. In this framework, model based as well as aggregative or divisive clustering algorithms can be utilized in order to produce the anatomical distribution of the neural network and possibly mimic the filament structure of cerebral connections. In addition, we aim at developing a statistical methodology (based on fMRI data) for constructing brain networks (as shown in Figure 1) that allow to control both the positive False Discovery Rate (pFDR) and the positive False Non-discovery Rate (pFNR).

The Institute of Molecular Physiology and Bioimaging of the National Research Council (IBFM-CNR) contributes with research activities aimed at developing methods to support the study, prevention, diagnosis, prognosis and treatment of neurological diseases. These includes: Statistical Parametric Mapping -SPM of PET, SPECT, MRI images, Support Vector Machine – SVM); 2) methods for Quantification of characteristic parameters of neurological diseases (Segmentation techniques of MRI images, for the estimation of volumes, eg. hippocampus in AD; Techniques for correction of physical effects on PET images – partial volume correction); 3) Methods for measuring brain connectivity under health and pathological conditions (Statistical Parametric Mapping -SPM of PET and MRI images for the study of connectivity in several cognitive domains – eg. memory); Methods of integration of biomedical parameters obtained for each subject using a variety of methods: diagnostic and in vivo functional PET, SPECT, CT, MRI imaging, ex vivo molecular imaging (histopathology, proteogenomics), response to therapy; multivariate analysis techniques – eg cluster analysis).

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