Project description
Imaging the activity of enzymes associated with disease will facilitate earlier diagnoses
Magnetic resonance imaging (MRI) is a non-invasive technology that generates high-resolution images of tissues and organs. Since its first use on a human being over 40 years ago, it has become instrumental in the diagnosis and monitoring of disease and injury. Functional MRI, invented in 1991, is based on the same principles but images metabolic activity indirectly via changes in blood flow. Its use has led to remarkable discoveries in biomedical research. Now, PRIMOGAIA is exploiting MRI technology to map and quantify enzyme activity in pathological tissue. Enzymes play critical roles in cellular metabolism and are already valuable biomarkers of pathology in blood tests. Now, their high-resolution spatial localisation in tissues will significantly enhance disease detection and monitoring.
Objective
PrimoGaia opens up a new pathway in Magnetic Resonance Imaging (MRI) by initiating the concept of in vivo “enzymatic imaging” for a better understanding of human physiology, early detection and prognosis of diseases, monitoring of therapeutic treatment. The main objective is to overcome current boundaries by making it possible to map and quantify the activity of an enzyme in a pathological tissue. It will be accomplished by building an MRI instrumentation operating at earth field in order to allow the use of 70MHz frequency for saturating the Electron Paramagnetic Resonance (EPR) transition of Nitroxyl radicals. Enzyme activity is assessed by the use of suitable probes designed to generate the radical upon action of the enzyme of interest. Upon saturation of the radical EPR resonance, polarization is transferred to the protons of the water molecules (Overhauser MRI). The enhancement factor will be high (more than two orders of magnitude). The polarized water signal thus reports on the local concentration of the radicals that reflect the enzymatic activity. 3 lines of activity will be addressed to generate the radicals of interest, namely: i) using a radical-containing molecular precursor that, upon the action of specific enzyme, yields a radical whose absorption frequency is sufficiently different to be selectively irradiated; ii) the use of paramagnetic impurities on nanodiamond surfaces to increase the OMRI effect; iii) the use of radical precursors as “prodrugs” generating a signal only after their activation. The overall methodology will be much less expensive than the current clinical scanners and will allow distribution in developping countries. PrimoGaia brings together an interdisciplinary consortium of research teams from 4 academics: Aix-Marseille University, U Mons, U Torino (reagents), CNRS Bordeaux (EPR unit, sequences, biology); Fraunhofer (Physics) and 2 companies: “Stelar” (magnetic unit) and “Pure Devices” an innovative SME (MRI instrumentation).
Fields of science
Programme(s)
Funding Scheme
RIA - Research and Innovation actionCoordinator
75794 Paris
France