Periodic Reporting for period 2 - GAMMA-MRI (gamma-MRI: the future of molecular imaging)
Okres sprawozdawczy: 2022-04-01 do 2023-09-30
The GAMMA-MRI project will develop a prototype for in vivo molecular imaging allowing the simultaneous exploitation of the sensitivity of gamma detection and the spatial resolution and flexibility of MRI. In the last decades, technological developments have been at the core of new imaging modalities, driving existing modalities with known physics principles to new levels enabling new routine clinical tools and opening new avenues for research, diagnoses and treatment. However, lack of sensitivity, low spatial resolution or even accessibility to devices all still hinder the applicability of medical imaging to address the major healthcare challenges of an ageing Europe. GAMMA-MRI is not just a hybrid approach combining separate modalities but a single new modality, simultaneously achieving the high spatial resolution of MRI and the high sensitivity of PET with faster scan times. Not requiring ultra-high MRI magnetic fields and expensive EM shielded rooms, nor detection of coincidence gamma rays as in PET, GAMMA-MRI will be less complex and thus less expensive than present state-of-the-art devices, especially hybrid ones.
The overall objectives of the GAMMA-MRI project are summarised below:
G1: Hyperpolarise efficiently several radioactive isotopes of xenon (mXe)
G2: Maintain mXe hyperpolarisation in vivo long enough to reach the targeted organ from the administration site
G3: Develop compressed sensing and AI-based strategies to obtain GAMMA-MRI images in minutes
G4: Integrate unique compact, fast, magnetic-field-compatible high-performance gamma detectors and electronics
G5: Build a prototype for in vitro and in vivo demonstration of the GAMMA-MRI technique
G6: Record the first in vivo GAMMA-MRI image of a rodent’s brain using the prototype and hyperpolarized mXe
The overall objectives of the GAMMA-MRI project are summarised below:
G1: Hyperpolarise efficiently several radioactive isotopes of xenon (mXe)
G2: Maintain mXe hyperpolarisation in vivo long enough to reach the targeted organ from the administration site
G3: Develop compressed sensing and AI-based strategies to obtain GAMMA-MRI images in minutes
G4: Integrate unique compact, fast, magnetic-field-compatible high-performance gamma detectors and electronics
G5: Build a prototype for in vitro and in vivo demonstration of the GAMMA-MRI technique
G6: Record the first in vivo GAMMA-MRI image of a rodent’s brain using the prototype and hyperpolarized mXe
We successfully produced, optimized and standardized the radiotracer mXe production. We developed a Spin Exchange Optical Pumping (SEOP) system and we tried to polarize three mXe isomers. With SEOP we achieved 18% polarization of 131mXe. Furthermore, we developed an easily modifiable NMR system for measuring the polarization of stable and mXe isotopes as an alternative technique to gamma detection. We tested for the first time the Dynamic Nuclear Polarization (DNP) technique on a quadrupolar nuclei, the 131Xe. The achieved polarization was measured by means of NMR but the signals acquired had a very low signal-to-noise ratio and the FID signal was relaxing very fast, thus it was technically difficult to quantify the degree of the achieved polarization. As a result, the DNP technique was decided to no be investigated further. Different sampling strategies were implemented into simulation software that included sequences of RF pulses, B-field gradients and estimated spin response for specific experimental conditions (e.g relaxation times), based on Bloch equations. We also developed a code to obtain realistic estimates of gamma signals. We used Monte Carlo simulation tools to estimate realistic gamma asymmetries in combination with external magnetic fields, RF sequences and HP nuclei. We are currently developing a low field GAMMA-MRI prototype, built around an optimized homogeneous permanent magnet. It requires fast gamma detectors along the main magnetic field axis and a further ring of them inside the MRI magnet. The work performed during RP1 was defining the technical specifications and references of the GAMMA-MRI prototype, design and order the necessary components.
GAMMA-MRI will go far beyond the SoA by developing a modality that records a single type of signals with the high resolution of MRI, the high sensitivity of PET, and the simplicity of SPECT. This will allow for sub-mm-resolution images using nano or even picomolar concentrations of tracer, by means of gamma detectors inside a low-field MRI magnet. Hyperpolarisation of gamma emitting nuclei leads to asymmetric gamma emission. MRI sequences depolarize the nuclei at a selected position in space, which lowers the gamma emission asymmetry. This approach can be several orders of magnitude more sensitive than signal pickup in RF coils, used in conventional MRI. We have the ambition to turn the method into a novel technology, GAMMA-MRI will be the imaging modality of the future. Our project provides the European leaders in science and technology with a competitive advantage to fully develop the GAMMA-MRI technique and make it applicable in pre- and clinical, multi-tracer, real time, high-speed, high-sensitivity imaging studies keeping Europe at the forefront of medical imaging.
The high-risk research we propose today will make GAMMA-MRI applicable in the clinic tomorrow. We will create new state-of-the-art in several technological aspects with the following science-to-technology breakthroughs: Hyperpolarisation of mXe & other tracers with Spin Exchange Optical Pumping & Dynamic Nuclear Polarisation. Storage and transport of hyperpolarised gamma-emitting tracers, separating hyperpolarisation and imaging. Fast, compact, high-sensitivity, high-count rates, magnetic-field compatible gamma detectors. Efficient data acquisition strategies shortening acquisition times to minutes. Encapsulation of tracers into biocompatible supramolecular constructs to preserve the hyperpolarisation longer, allowing to reach a distant targeted organ and eventually include biosensing capability.
Achieving our vision will require several challenging scientific and technological contributions to be made, namely: New generation of detectors, magnetic compatible, with better energy resolution than current ones in PET and SPECT. Use of AI-based acquisitions can also help in conventional MRI, reducing the acquisition time up to 100×. This allows a high increase in the number of procedures that can be done and will impact the availability of MRI equipment at the healthcare facility. While in this project we focus on brain perfusion studies, the technique is directly applicable to other organs and diseases. Stroke unit and Nuclear medicine departments will be the first to benefit from the technique.
By using our prototype we want to prove the efficiency of the technique to manage stroke early, by investigating them in an established rodent model of stroke (MCAO). After showing the viability of the technique we will be able to take part in clinical studies testing its utility in critical care of stroke patients. After commercialisation, we expect the device to cost less than 100k€, 10x less than any other existing molecular imaging modality, thus increasing accessibility to molecular imaging at point-of-care and, by improving stroke management, impact significantly the health and quality of life of patients. As lower magnetic fields will be possible, the devices will be smaller, portable, limiting drastically MR safety concerns and thus more patient friendly. GAMMA-MRI will provide innovations in the technologies involved that will have a broader application. New jobs will be created in the companies) commercialising the hardware and software,and in the industrial member of our consortium. Last but not least, shifting the current medical imaging devices paradigm to adaptable, simpler and lower cost devices, GAMMA-MRI could have a real impact on budget savings in the European healthcare system.
The high-risk research we propose today will make GAMMA-MRI applicable in the clinic tomorrow. We will create new state-of-the-art in several technological aspects with the following science-to-technology breakthroughs: Hyperpolarisation of mXe & other tracers with Spin Exchange Optical Pumping & Dynamic Nuclear Polarisation. Storage and transport of hyperpolarised gamma-emitting tracers, separating hyperpolarisation and imaging. Fast, compact, high-sensitivity, high-count rates, magnetic-field compatible gamma detectors. Efficient data acquisition strategies shortening acquisition times to minutes. Encapsulation of tracers into biocompatible supramolecular constructs to preserve the hyperpolarisation longer, allowing to reach a distant targeted organ and eventually include biosensing capability.
Achieving our vision will require several challenging scientific and technological contributions to be made, namely: New generation of detectors, magnetic compatible, with better energy resolution than current ones in PET and SPECT. Use of AI-based acquisitions can also help in conventional MRI, reducing the acquisition time up to 100×. This allows a high increase in the number of procedures that can be done and will impact the availability of MRI equipment at the healthcare facility. While in this project we focus on brain perfusion studies, the technique is directly applicable to other organs and diseases. Stroke unit and Nuclear medicine departments will be the first to benefit from the technique.
By using our prototype we want to prove the efficiency of the technique to manage stroke early, by investigating them in an established rodent model of stroke (MCAO). After showing the viability of the technique we will be able to take part in clinical studies testing its utility in critical care of stroke patients. After commercialisation, we expect the device to cost less than 100k€, 10x less than any other existing molecular imaging modality, thus increasing accessibility to molecular imaging at point-of-care and, by improving stroke management, impact significantly the health and quality of life of patients. As lower magnetic fields will be possible, the devices will be smaller, portable, limiting drastically MR safety concerns and thus more patient friendly. GAMMA-MRI will provide innovations in the technologies involved that will have a broader application. New jobs will be created in the companies) commercialising the hardware and software,and in the industrial member of our consortium. Last but not least, shifting the current medical imaging devices paradigm to adaptable, simpler and lower cost devices, GAMMA-MRI could have a real impact on budget savings in the European healthcare system.