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Non invasive quantitative molecular imaging with applications for studying cellular processes in oncology and neurology

Research project P6/38 (Research action P6)

Persons :

Description :

Molecular imaging has become an essential tool in biomedical research. It builds on technical advances in both clinical and small animal imaging techniques and exploits specific molecular and cellular targets as the source of image contrast. Imaging modalities such as MRI (Magnetic Resonance Imaging), PET (Positron Emission Tomography), SPECT (Single Photon Emission Computed Tomography), CT (Computed Tomography) and Echography used in the clinic have been miniaturized and are currently used to study small animals with high spatial resolution. Non invasive optical imaging technologies such as Bioluminescence Imaging (BLI) and fuorescence imaging have been developed in small animals and contributed substantially to the development of the entire new field of ‘imaging gene expression’ using reporter genes.
Different imaging strategies allow to probe complex biologic interactions dynamically, to study disease pathogenesis and to test the effect of therapeutic interventions in intact living systems over time. With these new tools come new challenges with respect to quantification and robust extraction of information from such data.

The overall objective of this IAP is to contribute to the refinement of existing molecular imaging procedures and the exploration of novel technologies with emphasis on methods to produce valid quantitative results. In vivo imaging strategies, involving advances in image acquisition, radiolabeled tracers and contrast agents, reporter gene strategies and image analysis will be investigated in the context of two life science research themes: cancer research and neurodegeneration. Both themes have in common that they focus on the characterization of the proliferation and/or the death of cells in their usual (micro)environment. Specific research questions to be addressed involve the assessment of gene expression and protein interactions, of stem cell migration and differentiation, of tumor metabolism and progression, of neurodegeneration and neuroprotection. Identifying and implementing the most appropriate imaging and image analysis methods to address these questions requires true scientific interaction between biomedical investigators and basic imaging scientists.

This aim will be reached by combining the expertise of teams from 5 Belgian universities in a network where the complementary nature of different imaging approaches available at the different universities are exploited. The methodologies that will be investigated include bioluminescence imaging, microPET, microSPECT, microCT , high resolution MRI and EPR imaging. The work is distributed in five work packages, that match with already ongoing or planned research activities of the different partners. Each of the work packages is taken care of by 2 or more partners and has been chosen to strengthen the extensive cooperation that already exist between partners at different institutions. These work packages encompass both life sciences research and fundamental research in core technologies.

Specific tasks are:

(WP 1) Cancer imaging Several imaging methodologies will be investigated and combined in order to acquire comprehensive and complementary functional and morphological information of tumor development and metabolism, to characterize the micro-environments in tumors and to understand the response to treatment.

(WP 2) Imaging of neurodegeneration and regeneration. Multimodal imaging techniques will be applied to study induced models of Parkinson disease in rodents and neuroplasticity in songbirds.

(WP 3) Development of radiolabeled tracers and MR contrast agents. High affinity ligands with specificity against molecular or cellular targets and metabolically responsive agents can either be radiolabeled, chemically conjugated to a reporter molecule or incorporated in a magnetic contrastophore. This core involves fundamental research on the selection, production and optimisation of these compounds, their biocompatibility and biodistribution and their in vitro and in vivo validation.

(WP 4) Image acquisition. This core encompasses the basic research on imaging physics and technology that is required to achieve optimal image quality with respect to spatial resolution, signal to noise ratio. For improving the spatial resolution of PET/SPECT novel reconstruction algorithms are being developed that incorporate anatomical information, provided by complementary modalities such as CT or MR. Noise reduction of images will be used to reduce acquisition times or radiation doses.

(WP 5) Image analysis. This core involves the development and validation of advanced image processing algorithms to derive quantitative measurements of structure and function from images, to fuse complementary information from multiple images and to compare images acquired at different time points, to build models of the underlying molecular processes and match them with the quantitative measurements

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