MRI (Magnetic Resonance Imaging) is a major tool for contemporary medicine and biological research, many progresses has been made since first years applications in the 1980’s. It uses high magnetic field for polarization and an electromagnetic field (Radio-Frequency domain) to interact with matter recovering the signal from proton resonance. It’s non invasiveness to acquire image of deep tissues by spatial encoding in 3 dimensions is a great advantage. Neuroimaging is one of the most important field of application and many progresses have been made to diagnose pathologies and to better understand brain functionality. Many other medicine application fields gain from using MRI, for its unreachable soft tissue contrast and it would be too long to cite all of them (musculoskeletal, cardiac, vascular…). Research and developments in MRI domain never stopped, it has gain to standard imaging, reducing the equipment prices and make them available in even small medical structures. Besides, development of new applications in direction of human functional imaging requires higher technologies: higher field strength, making the whole technology more complicated and expensive with increasing direct and exploitation costs.
With this project PRIMOGAIA, we attend to explore another way to approach some human body functions, not targeted up-to-now by conventional MRI or other imaging modalities. Using an enhancement process, known as Overhauser effect, developed in few research center around the world and, since year 2003, at CRMSB, our CNRS laboratory in Bordeaux, France, coordinator of the project. It phenomenon took place in water or tissues (human body consist of more than 70% of water), when a specific molecule with an unpaired electron, we will call it “nitroxide contrast agent”, is present. This electron can be excited by a resonance phenomenon using another RF electromagnetic wave, increasing drastically the signal intensity at the location of electron-proton interaction. It results on the images by an intense signal at the interaction locations, giving a highly contrasted image. The goal of the project is to develop and do MRI with more sophisticated nitroxide contrast agent, to assess human functions “disorders” appearing in some pathologies. In our oblectives this constructed molecule is made sensitive to certain enzyme present in pathologies or is able to targetbiological receptors. When the enzymatic process took place it affects the contrast agent molecule, at the end leaving the nitroxide part free and able to generate signal enhancement. Thus theses smart molecules can be used to detect theses specific enzymatic activities, linked to pathologies (pulmonary COPD) or pancreatitis for example). The project gain from years of accumulated experience of all partner’s and has already proved the in-vivo non-toxicity of such contrast agents. For this a new instrumentation has to be build, based on very low magnetic field or Earth Magnetic Field.
To target this objective PRIMOGAIA project is built around a European consortium of 7 partners from 4 different countries which gather 4 research laboratories and 2 SME’s. One group is responsible for instrumentation development and another is involved in bio-chemistry. The developments will be made and proof validated on a small size demonstrator. While a human body sized demonstrator will be constructed step by step to overcome all locks and make a proof of concept, giving a breakthrough in molecular imaging domain. It will open a new imaging domain involving standard and cost effective technologies, making them available anywhere around the world, even for countries without high end technology and support.

For this first year, the instrumentation group and the chemistry group, were mainly working on their own knowledge, but at the same time, there was many exchange and discussions between them, in order to better define and consolidate the main project objectives. This work has been reported into two reports: equipments specifications and description of all chemistry paths used to develop “smart” contrast agents. Theses “smart” contrast agents will target pathologies and/or linked enzymatic biological activities. Following a small sized equipment called “first kernel” has been developed in is now running (Pure-Device and Fraunhofer, Germany). This small kernel system is able to do MR imaging at low-field, with magnetic field optimization in direction and homogeneity. One image at Earth field has been produced, this system is fully software controlled. The design of this control electronics is such that it will be able to drive either the small kernel experimental system or the full sized equipment in good time. The specification basis allows to start the development of the final experiment setup. Stelar, Italy, designed a whole body sized pre-polarization magnet and developed fully controlled power supply.
On the chemistry group side, preliminary processes were involved to create the first molecular bricks being evaluated at Earth magnetic field. New compounds, like Nano-diamonds particles from University of Mons, Belgium, and nanoprobes created at Torino University, Italy, have been prepared and send to CNRS Bordeaux, for Earth field NMR characterization. Aix-Marseille University, France, has delivered molecules used to produce Ketone (usable as nitroxide contrast agent) by in-vitro enzymatic reaction for DNP test purposes. Nano-diamonds are ready to be tested for DNP experiment, but it needs some complementary instrumentation development, at least a new RF coil specific to the frequency domain.
During this period the working group in charge of instrumental integration, at CNRS Bordeaux, started to characterize the DNP process at Earth field on the basis of known nitroxide molecules that will be involved in future contrast agent. In parallel this group refined the Overhauser theory in the context of Earth magnetic field for these nitroxide molecules. With a homemade spectrometer working at Earth field and a developed radio-frequency channel, DNP experiment were conducted. At this time in-vitro preliminary DNP results has been produced for standard Nitroxide (Oxo-Tempo) and for Ketone issued from an enzymatic reaction.

The members of this project as everyone in the world had their work impacted by the pandemic situation reducing the working capabilities of many partners, especially for chemistry laboratory. However, the first steps and results of the project were substantial, each participant affording original ideas in instrumental or contrast agent chemistry, developments. At this time, imaging at low or Earth magnetic field is already made possible thanks to innovative concept developed in the instrumentation team (A patent is under writing). These first results will give the opportunity to explore DNP imaging in the next months. Our priority is now to get the opportunity to publish these first encouraging DNP results.
The running pandemic situation, at least in Europe, reduces the opportunity to communicate about the project and its results to large public audience.