The future of ultra-high field MRI and fMRI for study of the human brain

Abstract

MRI and fMRI have been used for about three and two decades respectively and much has changed over this time period, both in the quality of the data and in the range of applications for studying the brain. Apart from resolution improvements from around 4 mm in the early days to below 0.5 mm with modern technology, novel uses of contrast have led to the ability to sensitize images to some of the brain's structural properties at the cellular scale as well as study the localization and organization of brain function at the level of cortical columns. These developments have in part been facilitated by a continuing drive to increase the magnetic field strength. Will the next few decades see similar improvements? Here we will discuss current state of high field MRI, expected further increases in field strength, and improvements expected with these increases.

Introduction

Scientific discoveries and technological advancements often go hand in hand. A prominent example of this relationship is the discovery of X-rays and its subsequent use in crystallography, leading to the discovery of the structure of DNA and the development of modern molecular genetics and the CT-scanner. Similarly, in optics, lens optimization in the early microscopes led to the discovery of red blood cells and bacteria, and the development of optical techniques such as photo-activated localization microscopy (PALM) and fluorescence resonance energy transfer (FRET) has revolutionized cell biology.

Technological advances in a number of fields have also made a significant impact in the field of neuroscience. MRI is an excellent example of this, as it has, since its initial introduction in the clinic in the late seventies and early eighties, rapidly become the main modality not only for clinical neuroimaging, but also for basic research into the structure and function of the human brain.

Like with other brain imaging techniques such as positron emission tomography and CT, MRI has experienced a number of major developments since its early years, and as a result the quality and breadth of applications has increased tremendously. One important technological development that has continued over the entire lifespan of MRI is the increase in magnetic field strength, made possible by improvements in design and technology of the magnet; in parallel, associated radio-frequency (RF) electronics and magnetic field gradients have continuously improved, facilitating the practical use of high field strength MRI systems. These field strength increases have improved the study of both the brain's function and structure, as they provide for increases in sensitivity, contrast, and resolution.

For example, the early work leading up to the invention of fMRI two decades ago was greatly facilitated by the availability of magnets with fields substantially higher than the 1.5 T operating field of conventional clinical systems. Thulborn's early work on the dependence of transverse dipolar (T₂) relaxation on blood oxygenation in cannulated blood vessels in rodents benefited from an increased contrast available at the relatively strong field of 4.3 T (Thulborn et al., 1981). Ogawa's early work on T₂* (a combination of dipolar and magnetic susceptibility effects) relaxation dependence on blood oxygenation in rat brain was performed at 7 T (Ogawa and Lee, 1990, Ogawa et al., 1990), and his group's early human fMRI work based on BOLD contrast was performed at 4 T (Ogawa et al., 1992). An additional enabling technology in the early development of fMRI was rapid gradient switching that made rapid scanning techniques such as echo planar imaging (EPI) possible (Bandettini et al., 1992, Kwong et al., 1992, Turner et al., 1993). In large part because of the increased magnetic susceptibility contrast at high field that underlies the BOLD effect, many of the major fMRI research sites now own 7 T human scanners. These systems allow fMRI with increased sensitivity, specificity, and resolution compared to their lower field predecessors (Triantafyllou et al., 2005, Yacoub et al., 2008, Uludag et al., 2009).

Structural MRI has also benefitted from the increased resolution and contrast available at high magnetic fields. For example, the better resolution achieved when going from 1.5 T to 3 T has improved the separation of gray and white matter, and enabled quantification of cortical volume, an important parameter for the longitudinal monitoring of disease progression. At fields ranging from 7 T to 9.4 T, magnetic susceptibility-weighted techniques have allowed improved visualization of small anatomical structures based on susceptibility differences between blood, iron, and myelin (Bourekas et al., 1999, Christoforidis et al., 1999, Li et al., 2006, Duyn et al., 2007, Cho et al., 2010, Budde et al., 2011). In the CNS, white matter fibers, vascular structures, and the layer structure of cortical gray matter are being revealed at resolutions of several 100's of microns (Duyn et al., 2007, Kang et al., 2010, Marques et al., 2010). The combination of such data with high resolution functional data available with high field fMRI offers unique opportunities for the study of the relationship between structure and function in the human brain.

Given these important advantages of high field MRI for the non-invasive study of the human brain, it is natural to ask the question, where does the push for high field lead to and where will it end? As is the case in many research fields, cutting-edge technology comes at a price. With MRI, this price is increased system complexity and cost, and possibly reduced versatility. The latter may mean some applications may have limited benefit from high field or not be possible on the highest field systems, due to limited bore size (on a head-only system) or other restrictions. Is this price outweighed by the expected improvements? Will high field MRI find widespread application and be used clinically? In this review, we will look at some of these issues with a focus on applications to the study of human brain.