Periodic Reporting for period 3 - GAMMA-MRI (gamma-MRI: the future of molecular imaging)
Periodo di rendicontazione: 2023-10-01 al 2024-09-30
The GAMMA-MRI project has successfully developed a prototype for in vitro and in vivo imaging that enables the simultaneous exploitation of the sensitivity of gamma detection and the spatial resolution and flexibility of MRI. Over recent decades, technological advances have been pivotal in elevating existing imaging modalities based on well-established physical principles, leading to new routine clinical tools and opening novel avenues for research, diagnosis and treatment. Nonetheless, challenges such as limited sensitivity, low spatial resolution, and restricted accessibility have continued to hinder the full potential of medical imaging in addressing major healthcare needs, particularly in the context of an ageing European population.
GAMMA-MRI has introduced not merely a hybrid approach combining existing technologies, but an entirely new imaging modality. It simultaneously achieves the high spatial resolution of MRI and the high sensitivity of gamma photons detection as in nuclear medicine techniques. Unlike conventional MRI or PET-MRI systems, GAMMA-MRI does not require ultra-high magnetic fields, expensive electromagnetic shielding, or coincidence detection of gamma rays, thereby resulting in a less complex and more affordable solution compared to current state-of-the-art systems, especially hybrid ones.
The key objectives that have been successfully achieved in the GAMMA-MRI project are:
G1: Efficient hyperpolarisation of several radioactive isotopes of xenon (mXe).
G2: Preservation of mXe hyperpolarisation long enough to reach the targeted object of interest from the administration site.
G3: Development of compressed sensing strategies to obtain GAMMA-MRI images.
G4: Integration of unique, compact, fast, magnetic-field-compatible, high-performance gamma detectors and electronics.
G5: Construction of a prototype device for in vitro and in vivo demonstration of the GAMMA-MRI technique.
The pioneering GAMMA-MRI project has demonstrated the feasibility of a new imaging technique, laying the foundation for future developments in accessible and high-performance diagnostic imaging using radioactive rare gases, such as xenon.
GAMMA-MRI has introduced not merely a hybrid approach combining existing technologies, but an entirely new imaging modality. It simultaneously achieves the high spatial resolution of MRI and the high sensitivity of gamma photons detection as in nuclear medicine techniques. Unlike conventional MRI or PET-MRI systems, GAMMA-MRI does not require ultra-high magnetic fields, expensive electromagnetic shielding, or coincidence detection of gamma rays, thereby resulting in a less complex and more affordable solution compared to current state-of-the-art systems, especially hybrid ones.
The key objectives that have been successfully achieved in the GAMMA-MRI project are:
G1: Efficient hyperpolarisation of several radioactive isotopes of xenon (mXe).
G2: Preservation of mXe hyperpolarisation long enough to reach the targeted object of interest from the administration site.
G3: Development of compressed sensing strategies to obtain GAMMA-MRI images.
G4: Integration of unique, compact, fast, magnetic-field-compatible, high-performance gamma detectors and electronics.
G5: Construction of a prototype device for in vitro and in vivo demonstration of the GAMMA-MRI technique.
The pioneering GAMMA-MRI project has demonstrated the feasibility of a new imaging technique, laying the foundation for future developments in accessible and high-performance diagnostic imaging using radioactive rare gases, such as xenon.
The GAMMA-MRI project has successfully laid the foundations for a novel medical imaging modality merging nuclear magnetic resonance techniques with gamma detection, offering a transformative approach to in vitro and potentially in vivo molecular imaging for preclinical and clinical applications. Throughout the project, major technical and scientific milestones were achieved, resulting in a functional GAMMA-MRI prototype and a set of tools and methods with strong potential for exploitation in academic and clinical settings.
One major achievement was the optimisation and standardisation of the production of two key xenon isomers, 129mXe and 131mXe, in two European nuclear reactors, a significant step forward in developing novel MR-based radiotracers.
Two Spin Exchange Optical Pumping (SEOP) systems were also developed, extensively tested, and validated through Nuclear Magnetic Resonance (NMR) and gamma-detection experiments, achieving over 40% polarisation for stable 129Xe and about 30% for radioactive 129mXe, a significant breakthrough supporting the GAMMA-MRI methodology.
A flexible NMR system was built, incorporating custom RF coils and digital electronics for precise monitoring of xenon polarisation, and facilitating indirect measurements through gamma-asymmetry detection after RF pulses. Simulation tools based on Bloch equations and Monte Carlo methods were developed to optimise the experiments and predict signal behaviour under varying conditions.
The project culminated in the construction of a low-field GAMMA-MRI prototype, built around a homogeneous permanent magnet integrating fast gamma detectors. Complete integration of RF coils, gradient systems, and shimming elements was achieved and successfully validated through ¹H and ¹²⁹Xe MRI experiments and gamma-asymmetry measurements, marking the first realisation of the GAMMA-MRI technique.
The GAMMA-MRI project outcomes are already influencing ongoing research activities. Key technical developments, including the SEOP systems and the integrated gamma-NMR modules, are being considered for further development and commercialisation. The project has led to several scientific publications, with others submitted for peer review and more in preparation, along with presentations at international conferences.
One major achievement was the optimisation and standardisation of the production of two key xenon isomers, 129mXe and 131mXe, in two European nuclear reactors, a significant step forward in developing novel MR-based radiotracers.
Two Spin Exchange Optical Pumping (SEOP) systems were also developed, extensively tested, and validated through Nuclear Magnetic Resonance (NMR) and gamma-detection experiments, achieving over 40% polarisation for stable 129Xe and about 30% for radioactive 129mXe, a significant breakthrough supporting the GAMMA-MRI methodology.
A flexible NMR system was built, incorporating custom RF coils and digital electronics for precise monitoring of xenon polarisation, and facilitating indirect measurements through gamma-asymmetry detection after RF pulses. Simulation tools based on Bloch equations and Monte Carlo methods were developed to optimise the experiments and predict signal behaviour under varying conditions.
The project culminated in the construction of a low-field GAMMA-MRI prototype, built around a homogeneous permanent magnet integrating fast gamma detectors. Complete integration of RF coils, gradient systems, and shimming elements was achieved and successfully validated through ¹H and ¹²⁹Xe MRI experiments and gamma-asymmetry measurements, marking the first realisation of the GAMMA-MRI technique.
The GAMMA-MRI project outcomes are already influencing ongoing research activities. Key technical developments, including the SEOP systems and the integrated gamma-NMR modules, are being considered for further development and commercialisation. The project has led to several scientific publications, with others submitted for peer review and more in preparation, along with presentations at international conferences.
The GAMMA-MRI project has gone significantly beyond the state of the art by developing a modality that records a single type of signal with the high spatial resolution of Magnetic Resonance Imaging (MRI), the high sensitivity of Positron Emission Tomography (PET), and the simplicity of Single Photon Emission Computed Tomography (SPECT). Through this approach, sub-millimetre resolution images have been obtained using only nano to pico molar concentrations of tracer, by means of gamma detectors integrated within a low-field MRI magnet. The project demonstrated that hyperpolarisation of gamma-emitting nuclei induces asymmetric gamma emission, and that MRI sequences can depolarise nuclei leading to measurable changes in gamma asymmetry. This technique has proven to be several orders of magnitude more sensitive than traditional RF signal detection in conventional MRI.
Our work has provided European leaders in science and technology with a unique competitive advantage in developing next-generation imaging modalities, applicable in preclinical and clinical settings for multi-tracer, real-time, high-speed, and high-sensitivity studies.
During the course of the project, several critical science-to-technology breakthroughs were accomplished:
- Efficient hyperpolarisation of metastable xenon isotopes (mXe) through Spin Exchange Optical Pumping (SEOP).
- Successful storage and transport of Hyperpolarized gamma-emitting tracers, enabling the separation of hyperpolarisation and imaging phases.
- Development of fast, compact, high-sensitivity gamma detectors compatible with magnetic fields and capable of high count rates.
- Development of advanced data acquisition strategies, including compressed sensing methods.
The project also delivered a low-field prototype GAMMA-MRI device, which successfully combined all these technological advances. Tests using 1H and 129Xe MRI, along with gamma-asymmetry detection experiments, demonstrated the technique's potential for revolutionary in vitro and possibly in vivo imaging applications.
GAMMA-MRI offers major advantages for healthcare: reduced device cost (estimated under €100,000), portability, enhanced safety through lower magnetic fields, and improved accessibility to molecular imaging at the point-of-care. Initially focused on brain perfusion and stroke diagnosis, the technology is adaptable to other organs and clinical applications. The project’s results are expected to create new jobs in the imaging and medical technology sectors, and to contribute significantly to budget savings in European healthcare systems by shifting towards simpler, more affordable imaging devices.
Our work has provided European leaders in science and technology with a unique competitive advantage in developing next-generation imaging modalities, applicable in preclinical and clinical settings for multi-tracer, real-time, high-speed, and high-sensitivity studies.
During the course of the project, several critical science-to-technology breakthroughs were accomplished:
- Efficient hyperpolarisation of metastable xenon isotopes (mXe) through Spin Exchange Optical Pumping (SEOP).
- Successful storage and transport of Hyperpolarized gamma-emitting tracers, enabling the separation of hyperpolarisation and imaging phases.
- Development of fast, compact, high-sensitivity gamma detectors compatible with magnetic fields and capable of high count rates.
- Development of advanced data acquisition strategies, including compressed sensing methods.
The project also delivered a low-field prototype GAMMA-MRI device, which successfully combined all these technological advances. Tests using 1H and 129Xe MRI, along with gamma-asymmetry detection experiments, demonstrated the technique's potential for revolutionary in vitro and possibly in vivo imaging applications.
GAMMA-MRI offers major advantages for healthcare: reduced device cost (estimated under €100,000), portability, enhanced safety through lower magnetic fields, and improved accessibility to molecular imaging at the point-of-care. Initially focused on brain perfusion and stroke diagnosis, the technology is adaptable to other organs and clinical applications. The project’s results are expected to create new jobs in the imaging and medical technology sectors, and to contribute significantly to budget savings in European healthcare systems by shifting towards simpler, more affordable imaging devices.