Donald B. Twieg, Ph.D. - US grants

technology /technique development; male; female; magnetic resonance imaging; human subject; nuclear magnetic resonance spectroscopy; biomedical resource; bioengineering /biomedical engineering; biological products;

In biomedical NMR imaging and spectroscopy, the increased NMR sensitivity in high-magnetic-field systems offers improved spatial and temporal resolution, as well as the ability to detect phenomena producing more subtle effects. The ability to usefully visualize biochemical distributions in tissues by MR spectroscopic imaging depends on the spatial resolution of the MR techniques available, and the ability to monitor dynamic biochemical or functional changes by MR techniques depends on the speed of the MR techniques available. The purpose of this technical project is to develop improved methods for rapid MRI, chemical shift (spectroscopic) MR imaging, and functional brain MRI, with spatial and temporal resolution exploiting the sensitivity of the high-field (4.1T) UAB system. Techniques are designed and tested in simulation studies, implemented and tested experimentally with the 4.1T MR system in phantom and volunteer studies, and once established, are incorporated into collaborative research protocols. [unreadable] This past year several new techniques were developed, and including (1) a rapid echo-planar imaging (EPI) technique utilizing a novel calibration procedure to prevent image defects in the presence of common and unavoidable imperfections in instrumental performance; (2) a novel processing technique for functional MRI which removes confounding systematic "noise" due to cardiac, respiratory, and other physiological effects; (3) a dual-echo snapshot spiral MRI technique for separation of activation-related signal changes from flow-related changes in fMRI; and (4) improved techniques for detecting the "Fast Response," a small fMRI signal dip occurring promptly following the onset of neuronal processing activity in the brain. The techniques developed here benefit collaborative projects and other technical Core projects of this Resource, and are available for use by other research laboratories. The new fMRI methods promise to improve the quality and sensitivity of functional brain studies. The calibrated EPI technique will provide enhanced rapid imaging capabilities in applications within our Resource core projects as well as collaborative projects.

This training grant has three positions per year that can be occupied by either MD or PhD fellows. The grant is for research training in the cardiovascular aspects of magnetic resonance. 4T projects are encouraged. Trainees interface well with core projects. In one recent study, they used 31 P spectroscopy with handgrip exercise to evaluate high energy phosphate metabolism in women with chest pain but normal coronary arteries. Approximately one third of these women had a positive study (i.e. ,PCr/ATP showed a significant fall compared with control subjects). While these initial studies were performed 1.5T, future studies will be performed on the 4.1T system for better resolution of P1 and observations of changes in pH.[unreadable]

ABSTRACT

A grant has been awarded to Dr. Gamlin at the University of Alabama at Birmingham (UAB) to acquire a state-of-the-art vertical, 4.7 Tesla, magnetic resonance imaging (MRI) device designed especially for use with alert, trained non-human primates. MRI, especially functional MRI, is an exciting new tool that is revolutionizing our ability to study the brain. However, this technology has limitations when applied solely to humans. A major limitation is that once a brain region is identified by fMRI as being functionally activated during a specific task, additional invasive, experimental options are limited. However, by using non-human primates, further studies are not limited to imaging alone. One can conduct electrophysiological studies using single- and multi-unit recording, and neuroanatomical and pharmacological inactivation techniques to significantly enhance the level of understanding of brain function. Therefore, this 4.7T MRI system will be used in a primate Neuroimaging Facility which, when combined with existing neurophysiological techniques, will be able to examine brain function at both microscopic and macroscopic scales and with temporal resolutions of milliseconds - experiments that are not currently feasible in humans. In addition, using this combination of techniques, new pulse sequences will be developed and validated to ensure that fMRI images more accurately reflect the spatial and temporal characteristics of the underlying neural activity.
UAB has assembled a group of internationally-recognized neuroscientists with expertise in studying the underlying mechanisms of visual, sensorimotor, and oculomotor processing in alert, behaving primates. The primate visual system is the most extensively studied primate sensory system and the oculomotor system is the best understood primate motor system. Thus, these UAB investigators are in a unique position to fully exploit fMRI techniques to better understand the behavior of these model neural systems and, in so doing, contribute to a deeper understanding of brain function in general. The planned research projects will include the investigation of neural mechanisms related to vision, eye movements, plasticity, and sensorimotor integration in occipital, parietal, temporal, and frontal cortex. Other projects will involve the development of better functional and spectroscopic MRI techniques.
The planned Neuroimaging Facility, which will be one of only a few facilities in the world in which research spanning single neurons to whole brain behavior can be conducted in the same research animal, will be developed into a regional/national resource for research in Neuroscience. This planned facility thus has the potential to make major contributions to the field of functional brain research. The planned Neuroimaging Facility will have a major impact on recruitment and training of students in this emerging research area. Specifically, to ensure that the next generation of scientists will exploit this resource fully and develop MRI techniques further, participating faculty will ensure that students are trained in-depth in both neuroscience and MRI imaging. Further, UAB's Comprehensive Minority Faculty and Student Development Program, the NSF-funded Alliance for Minority Participation, and the Alliance for Graduate Education and the Professoriate Program, will ensure that a significant proportion of these students are from underrepresented groups.

Throughout the development of in vivo NMR spectroscopy and imaging, there has been a push towards the utilization of higher field strengths and their inherent advantages of increases SNR and spatial and spectral resolution. However, only recently has it been demonstrated that the technical hurdles associated with high field NMR studies of humans can be overcome to accrue these advantages. This demonstration of the advantages of high field human NMR has in turn fueled the growth of high field (3 and T) systems. The majority of the users of these systems have focused their efforts on functional imaging of brain, with significantly less effort expended on the development and application of spectroscopic imaging, quantitative imaging and cardiac imaging into clinically useful protocols. To fully utilize the advantages of high field NMR in these areas, significant technological development and validation in meaningful clinical studies must occur. Therefore, the overall goal of this proposal is to develop a high field clinical NMR spectroscopy and imaging research resource. To achieve this goal we will focus on the development and implementation of : 1) advanced and novel methods to acquire unique data (such as the TA cycle rate, or ultra high temporal and spatial resolution functional images) which are either not possible or not routinely available on most commercial systems (both high and low field) and 2) enhance our ongoing clinical collaborations with novel methods for quantitative imaging and spectroscopy, thereby extending the state of the art in clinical NMR studies. Specifically, we will: 1) develop new spectroscopic imaging measurement to acquire ultra high redolution spectroscopic images of metabolites and map the TCA cycle rate: 2) improve the state of the art in rapid functional imaging through novel approaches of spiral scan imaging: 3) extend the current state of the art in high field imaging to permit quantitative imaging and its application in patients; 4) develop and implement clinically useful cardiac imaging methods; and 5) provide a common resource for the development of sophisticated metabolic modeling, experimental design and analysis software tools fro these protocols. These goals are intended to advance the state of the art in high field imaging and spectroscopy from a research curiousity to a powerful and clinically viable investigation tool.

[unreadable] DESCRIPTION (provided by applicant): [unreadable] Contemporary magnetic resonance imaging (MRI) methodology involves an implicit assumption, which is computationally convenient but physically inaccurate. This R21/R33 project seeks to develop a novel MRI methodology which abandons this assumption, thereby avoiding defects which commonly afflict rapid single-shot MR images. Because it interprets MRI raw data more accurately, the new methodology promises also to permit fundamentally more efficient, accurate and robust measurements to be made in several general types of MRI applications, such as diffusion imaging, measurement of tissue relaxation parameters, flow and motion imaging, and blood perfusion imaging. A strength of the general approach is that it measures tissue parameters more directly than do established approaches, which infer parameters from multiple separately acquired images. In an initial investigation and development of this methodology (termed PARSE), this project will implement a single-shot PARSE method, SS-PARSE, which is especially well-suited to functional MRI (fMRI) of the brain, with several theoretical advantages over existing methods used in fMRI. These theoretical advantages in accuracy, acquisition speed, and robustness, are substantiated in initial simulation trials. The immediate goal of the R21 project will be to experimentally verify these expected performance advantages of the SS-PARSE technique in well-controlled imaging studies using phantom objects in a 4.7T vertical-bore primate MR imaging system. A shortcoming of the methodology is that it requires much longer computation times than conventional MRI approaches. The R21 project will seek to develop much faster computational algorithms, and will determine the prospects for reducing computational time to roughly that of typical conventional fMRI studies. If these two major performance milestones have been met, the R33 project will commence, testing and characterizing the new methodology in functional brain imaging studies of primates. Additionally, the R33 project will include development of more sophisticated versions of the SS-PARSE method for high-resolution functional imaging. The project promises to introduce a new methodology, which may have substantial fundamental performance benefits over a broad range of clinical MRI applications. [unreadable] [unreadable]