IMAGO project has the ambitious objective to develop nuclear magnetic resonance imaging (MRI) with a resolution down to the micron scale. Considering that currently, the resolution of clinical MRI is about 1mm while the intrinsic resolution of molecular diffusion MRI (DMRI) is about 10-20 micrometres, the technology proposed to represent a clear advance on the state of the art. This scientific breakthrough requires the integration of optical and nuclear magnetic resonance (NMR) imaging that nowadays remains a challenge.
Optical imaging, like fluorescence microscopy, is able to visualise in vitro with submicron resolution the different cellular and subcellular compartments and determine their size, shape and dynamics but optical imaging suffers from scarce light penetration in tissues making it unusable for in vivo diagnostics.
The breakthrough idea we propose is that of linking the sub-cellular submicroscopic information of the optical to the mesoscopic and millimetric information directly observable through MRI. This is possible by exploiting the poorly explored fundamental concept of anomalous diffusion, our experimental experience in the field of NMR imaging in anomalous diffusion and light behaviour in complex systems.
The core strategy to integrate optical and MRI information resides in the manufacture of multiscale porous standard samples. These calibration standards of known characteristics will be used to perform anomalous diffusion experiments using both diffusion NMR and single-particle tracking (SPT) optical modality techniques. From comparison and integration of NMR diffusion and optical imaging data obtained with fluorescent and 19F-labeled molecular probes, we will identify the parameters of DMRI more sensitive to submicroscopic variations evaluated with SPT. After linking specific submicrostructural characteristics to the variation of certain mesoscopic NMR parameters we will elaborate NMR data fit functions that will allow increasing the resolution of DMRI investigations.
Specific objectives of IMAGO are 1) Design and achieve phantoms with multiscale ad hoc features for anomalous diffusion investigations with both STP and DMRI methodologies; 2) Investigate and overcoming the limits of integration between the optical tracer and diffusion NMR in calibration standards; 3) Translating theoretical models to functions fitting experimental data; 4) Proof of concept: validate the new protocol in extracted tissues of mouse spinal cord comparing anomalous diffusion MRI results with conventional diffusion MRI and histology investigation.
A strong impact of this project is expected in 5-10 years, with dramatic improvement in medical diagnostics and a consequent huge benefit for the EU citizens. In a long-term vision, MRI characterised by subcellular spatial resolution will enter in the clinical routine opening up new possibilities in terms of early diagnostic, new drugs development, therapeutic strategies and patients handling.
Costantini, G., Capuani, S., Farrelly, F.A. et al. A new perspective of molecular diffusion by nuclear magnetic resonance. Scientific Reports 13, 1703 (2023). https://doi.org/10.1038/s41598-023-27389-7