Experimental neuroscience and clinical research are only two of the main research fields, either basic or applied, where magnetic resonance imaging (MRI) is considered as a main resource. The practical applications of MRI, including diagnostics, are of primary importance. The key features of MRI that caused this success include the fact that it is non-invasive and can produce extremely versatile contrast even without external contrast agents. The latter is related to the proper manipulation of NMR signal that can be sensitized to several biophysical and biological phenomena, including molecular dynamics, water diffusion, blood perfusion, metabolism, tissue magnetic properties, chemical exchange phenomena, pH, temperature, and many others. NMR applications are continuously evolving, and there is opportunity for many technological advances that can be easily exploited as MRI contrasts in clinical applications.

Microstructural damage is indeed a common, key point for the characterization and understanding of many serious neurological and psychiatric diseases and disorders, including neurodegenerative diseases, chronic alcoholism, diabetes, postconcussive syndromes and brain injuries, radiation-induced injuries, migraine, schizophrenia, and many others. In this project we are developing of a set of advanced MR techniques for the characterization of microstructural damage in some key applications, on the validation of these techniques on animal models, and finally on the translation of these techniques to pilot clinical studies. Albeit different pathophysiologically, many brain diseases share two common needs: the need of proper, quantitative tools for characterizing the specific mechanisms underlying tissue damage, and the need of diagnostic tools that can identify the pathology at its earliest stages before manifestation of severe clinical symptoms and can assess even subtle efficacy of experimental treatments.

The main form of microstructural damage shared by many neurological diseases is related to myelin sheath breakdown. Quantification of myelin is thus critical for the assessment of a variety of neurological diseases including Multiple Sclerosis (MS. The techniques we are developing have a potential specific sensitivity to demyelination. Truly “tissue-composition-specific” MRI measures would be a tremendous advance, as it would allow monitoring of the effect of treatments geared toward specific pathologic processes (e.g. myelin repair, neuroprotection, iron deposition), as well as help clarify the pathophysiologic basis of myelin-related diseases.

Objectives

Primary objectives of our research are to assess in living rodents if the MRI techniques we are developing are able to assess the myelin content, used alone, or in conjunction with conventional MR approaches, and to extend these results to humans.

Secondary aims will be to develop appropriate multiparametric processing approaches, capable to improve the quantitative information that can be extracted from the data, and to assess if our techniques are sensitive to dynamic changes, i.e. if they are capable to detect demyelination and remyelination.