Upgrading our view of Growing Older: Mapping Brain Changes across the Lifespan with Ultra High Field Multi-Spectral MRI
Lead Research Organisation:
CARDIFF UNIVERSITY
Department Name: Sch of Psychology
Abstract
The initial data transmitted from the James Webb Space Telescope have recently dramatically reminded the world that scientific understanding can be transformed by the improvement of image spatial resolution. Since the invention of magnetic resonance imaging (MRI) in 1973, similar breakthroughs in its spatial and temporal resolution have been key to its use in discovery science. Until we have access to the fine details of any process, we have no idea of the level of granularity that will be required in its modelling to provide satisfactory explanations and testable predictions.
It has recently been recognized that the human brain's axons continue to become myelinated after birth and into adulthood; that this myelination is largely driven in a bootstrapping process by each neuron's experience; that the pattern of myelination in each cortical area defines the most important microcircuits in that area, where horizontal myelinated fibres are likely to carry inhibitory signals; and that brain MRI contrast is conveniently almost entirely dependent on the amount of myelin within each image voxel. In consequence, the generation of in-vivo MR brain images with a spatial resolution sufficient to distinguish and quantify myeloarchitecture has become a uniquely important goal in the study of human brain function. General population-wide trends in myelogenesis during development, and individual differences, may become key explanatory observations for cognitive psychology and the basis of empirical biomarkers in psychiatric disorders. At the same time, we have started to understand that the mechanisms of brain energy supply and consumption vary with age, and they may be closely related with changes in synaptogenesis and myelination across the lifespan.
The attainable resolution in MRI depends on three main factors: the strength of the applied magnetic field, the efficiency of the radiofrequency receiver coil and its electronics, and the ingenuity of the sequences of RF and gradient field pulses employed in capturing the magnetic resonance signal. Currently the highest MRI field strength for which the engineering requirements are tractable is 7 Tesla, introduced for human-size scanners in about 2000, and the number of such scanners installed globally is approaching 100.
Like many other medical technologies, MRI continues to undergo rapid development driven by Moore's Law, optoelectronics, maturing hardware design techniques, and strong market competition. Thus the first generation of 7T scanners, including the pioneering Siemens Magnetom scanner installed at CUBRIC in 2015, is now technologically far behind more recently marketed systems, such as the Siemens Terra scanner and the new GE 7T Signa. While the CUBRIC 7T scanner continues to outperform comparable 3T scanners in many respects, its ancillary hardware, computer equipment, and software environment leave it unable to deliver the feasible goal of acquiring isotropic 0.5 mm resolution images of brain quantitative microstructure and functional activity. This makes it unsuitable for cutting-edge studies (for example) of cortical changes in adult subjects learning new skills, of myeloarchitectural abnormalities in the brains of schoolchildren with behavioural problems, and of the sequence of cortical area maturation in the development of new visual skills, and to relate all of these changes to the changes in brain metabolism and the maintenance of healthy perfusion with age.
The proposed upgrade will enable CUBRIC to investigate how the brain develops and maintains healthy function across the lifespan, a crucial research question as the world population live longer than ever.
It has recently been recognized that the human brain's axons continue to become myelinated after birth and into adulthood; that this myelination is largely driven in a bootstrapping process by each neuron's experience; that the pattern of myelination in each cortical area defines the most important microcircuits in that area, where horizontal myelinated fibres are likely to carry inhibitory signals; and that brain MRI contrast is conveniently almost entirely dependent on the amount of myelin within each image voxel. In consequence, the generation of in-vivo MR brain images with a spatial resolution sufficient to distinguish and quantify myeloarchitecture has become a uniquely important goal in the study of human brain function. General population-wide trends in myelogenesis during development, and individual differences, may become key explanatory observations for cognitive psychology and the basis of empirical biomarkers in psychiatric disorders. At the same time, we have started to understand that the mechanisms of brain energy supply and consumption vary with age, and they may be closely related with changes in synaptogenesis and myelination across the lifespan.
The attainable resolution in MRI depends on three main factors: the strength of the applied magnetic field, the efficiency of the radiofrequency receiver coil and its electronics, and the ingenuity of the sequences of RF and gradient field pulses employed in capturing the magnetic resonance signal. Currently the highest MRI field strength for which the engineering requirements are tractable is 7 Tesla, introduced for human-size scanners in about 2000, and the number of such scanners installed globally is approaching 100.
Like many other medical technologies, MRI continues to undergo rapid development driven by Moore's Law, optoelectronics, maturing hardware design techniques, and strong market competition. Thus the first generation of 7T scanners, including the pioneering Siemens Magnetom scanner installed at CUBRIC in 2015, is now technologically far behind more recently marketed systems, such as the Siemens Terra scanner and the new GE 7T Signa. While the CUBRIC 7T scanner continues to outperform comparable 3T scanners in many respects, its ancillary hardware, computer equipment, and software environment leave it unable to deliver the feasible goal of acquiring isotropic 0.5 mm resolution images of brain quantitative microstructure and functional activity. This makes it unsuitable for cutting-edge studies (for example) of cortical changes in adult subjects learning new skills, of myeloarchitectural abnormalities in the brains of schoolchildren with behavioural problems, and of the sequence of cortical area maturation in the development of new visual skills, and to relate all of these changes to the changes in brain metabolism and the maintenance of healthy perfusion with age.
The proposed upgrade will enable CUBRIC to investigate how the brain develops and maintains healthy function across the lifespan, a crucial research question as the world population live longer than ever.
Technical Summary
Ultra-high field (UHF) MRI (7T and above) provides increased sensitivity to subtle brain changes thanks to the improved spatial resolution and access to MRI measurement that are simply unfeasible at lower field strength. While the CUBRIC's 7T scanner continues to outperform comparable 3T scanners in many respects, its ancillary hardware, computer equipment, and software environment leave it unable to deliver the feasible goal of acquiring isotropic 0.4 mm resolution quantitative structural images, and 0.5 mm resolution images of brain functional activity-which is essential for characterising cortical changes occurring with age. With this proposal we seek funding to upgrade our 7T platform to the Siemens Terra platform. The upgrade will include: 1) a new computer architecture, supporting much faster image reconstruction, thus enabling handling of higher resolution datasets; 2) a novel unit for parallel transmission, which is essential at UHF to achieve radio-frequency (RF) field uniformity: we will work on developing real-time, patient-specific RF pulses, which will automatically correct for patient movement, always ensuring maximum safety (including scanning infants) and image quality; 3) new multi-nuclear solutions, and in particular deuterium, a promising alternative to positron emission tomography for metabolic imaging of glucose uptake and oxygen metabolism. These innovations combined with ongoing developments of motion correction strategies and methods to measure arterial stiffness will equip us to fully harness the potential offered by UHF and apply it to the study of brain changes occurring throughout the lifespan, and their association with cognitive function and behaviour. In summary, this upgrade will enable the development of novel solutions for MRI at 7T, with the goal of mapping microstructural cortical changes and associated modifications in glucose metabolism across the lifespan, and of cortical changes in adult subjects learning new skills.
