Magnetic Resonance Imaging is a powerful diagnostic technique, widely applied in the clinic and in pre-clinical research. Magnetic contrast agents are routinely used to enhance image contrast, and help discriminate between different tissues, or between pathological and healthy states. Objective of this project is the development of novel probes for Magnetic Resonance Imaging applications. Specifically, we aim to:

• develop MR imaging nanosensors capable of reporting quantitatively on the cellular and tissutal microenvironment;
• increase molecular specificity and sensitivity of MR contrast agents;
• design nanoprobes that exploit specific physiological transport mechanisms to target cellular and tissue compartments otherwise inaccessible to conventional contrast agents;
• develop MR imaging methods and image analysis approaches to exploit the full potential of novel imaging probes.

Specific projects we are currently pursuing include:

Development of ratiometric magnetic nanosensors

Recent studies have shown that T2 MR relaxivity of magnetic nanoparticles depends of their aggregation state, and increases when particles are assembled forming larger aggregates. This phenomenon can be exploited to develop magnetic nano-probes that are sensitive to the presence of molecular targets that promote cross-linking between particles, or to enzymatic activity that breaks up multi-particle assemblies. The goal of this research is to design a ratiometric magnetic nanosensors that exploits aggregation-induced T2 contrast enhancement together with the parallel measurements of a parameter independent (or less dependent) on the aggregation state, such as T1 Relaxation Rates.

High-relaxivity magnetic nanoparticles for Cerebral Blood Volume (CBV) measurements

Functional MRI, i.e. MRI as applied to map brain function, relies on the Blood Oxygenation Level Dependent (BOLD) phenomenon. Alternative methods, like fMRI based on Cerebral Blood Volume measurements, may provide increased contrast-to-noise ratio, and to the possibility to reduce susceptibility-artifacts through the use of spin-echo methods. However, CBV MRI requires the use of blood pool contrast agents to sensitize the images to haemodynamic changes. We are developing a new class of iron oxide nanoparticles with large saturation magnetization and able to obtain stronger CBV-weighting, whilst reducing the systemic nanoparticles load and potential safety risks.

Mapping altered neurofunctional states with multi-parametric Magnetic Resonance Imaging

We deploy a high-resolution morpho-anatomic methods (diffusion-tensor imaging and tractrography, diffeomorphic mapping of cortical thickness, voxel-based morphometry, tract-based spatial statistics of fractional aniostropy) in combination with high-resolution measurements of resting and evoked brain function (e.g. functional and pharmacological MRI). The integration of functional and structural parameters offers the unprecedented opportunity to obtain a multidimensional view of the functional and structural architecture of the brain in CNS disease states (collaboration with dr. V. Tucci and F. Papaleo, IIT Genova and dr. Scattoni, ISS Roma).

Fig.1: Left: High resolution (90 um3) T2-weighted image of the murine brain. Middle: 3D-segemented reconstruction; Right: High resolution white matter tractrography.

Multimodal MRI

The goal of this activity is to simultaneously record anatomical and functional MRI signals in vivo with complementary investigational techniques, such as multi-electrode electrophysiology (collaboration with prof Vassanelli, Padova), optical methods (Prof Gian Michele Ratto, Pisa) and metabolic probes (tissue oxymetry) to validate MRI signals of interests. Hybrid optical and MR systems may allow the combination of molecular targeting capacity imparted by fluorescent reporter probes with the versatile tissue-function contrast achieved with MRI. The combination of electrophysiological or tissue oxymetry signals with fMRI measurements can greatly help investigate the origin of positive and negative haemodynamic responses.

Linking circuit to behavior: pharmacogenetic and optogenetic modulation of fMRI responses

The research line aims to combine advanced pharmacogentic and optogenetic methods to dissect the circuital basis of behavior using spatially-resolved fMRI or phMRI techniques. When combined with behavioral measurement, the technique has the potential to map the downstream circuits engaged by specific neuronal population and to associate this signature to specific behavioral or pathological traits (collaboration with Prof. Benfenati, IIT Genova).

The Magnetic Resonance Imaging (MRI) unit at CNI@NEST hosts a 4-channel Bruker 7.0 Tesla magnet system, and is equipped with state-of-the-art technology for physiological monitoring (blood pressure, oxymetry, bloog gas levels, ECG, respiratory and cardiac frequency). Advanced image processing and analysis methods are developed in close collaboration with external groups of established reputation in the field of image analysis and pattern recognition (Prof. Murino, IIT Genova; Prof Tsaftaris, IMT Lucca).