We developed advanced MRI approaches based on non-adiabatic relaxation called RAFFn (RAFF of rank n), studying in particular the ranks n=4 and 5. These are especially sensitive to slow molecular motion, and we showed that they are sensitive to myelin damage. We measured myelin content and integrity in the normal brain and in complex pathologies in rodents. We obtained very high correlation between relaxation and myelin content as assessed by quantitative histology. Importantly, the correlation we obtained is much improved compared to what can be achieved with conventional MRI approaches. Sensitive detection of demyelination was possible in various brain areas, with different tissutal properties.
We developed also functional imaging methods, in order to identify the functional correlates of microstructural damage. Our efforts were focalized in two fields: steady state functional connectivity and neuromodulation. Functional connectivity is an approach that quantifies the network behavior of the brain, and is especially attractive for pathologies because it characterizes the cortex as a whole. Neuromodulation, that is a byproduct of some of the MRI techniques we developed, is important as well, because allows isolating specific neural processes, and can be used in therapeutic interventions, for instance in Deep Brain Stimulation (DBS) in Parkinson’s and in other neurodegenerative diseases.
Main results we obtained include a study on semantic network in Alzheimer ’s disease (AD), that showed that in mild AD brain regions belonging to the semantic control network are abnormally connected not only within the network, but also to other areas known to be critical for language processing. We also studied the nature of impulsive control disorder in Parkinson’s disease, which greatly exceed the previously envisioned dopaminergic pathways as the only culprit. Finally, we showed that our innovative approaches to DBS have the potential to improve the patient’s treatment, being easily tailored to the needs of each single patient.
Given the complex features of microstructural damage, it is likely that a multiparametric integration of different metrics is needed, where the new approaches we propose are intended to complement other quantitative techniques. MRI in itself lends naturally towards multiparametric studies, because it can produce images sensitized to multiple contrast mechanisms, as described above. MRI can also be combined with compatible approaches, including PET based molecular imaging, electrophysiological measurements and neuromodulation. In this project, we implemented an appropriate set of processing tools to combine different kind of information. Main results obtained with this approach are related to Parkinson Disease (PD) and the associate idiopathic REM sleep behavior disorder (iRBD). We were able to show that rotating frame relaxation methods, along with functional connectivity measures, are valuable to characterize iRBD and PD subjects, and with proper validation in larger cohorts these approaches may provide pathological signatures of iRBD and PD.
