EXCEED THE SPACE PROVIDED. Nuclear magnetic resonance imaging (MRI) is now a major diagnostic tool. However it is still used primarily in a qualitative fashion. We believe that a thorough and potentially quantitative understanding of signal changes observed in clinical MRI requires knowledge of how the basic building blocks of tissues behave, i.e. single cells. An understanding of the biophysical origins of MR signals is a recognised need for the full potential of MR to be realised. Nuclear magnetic resonance (NMR) microimaging has enabled the direct examination of large single cells. In the last funding cycle, we have been determining the water T1, T2 and multicomponent apparent diffusion coefficient (ADC) in single neurons, blood cell ghosts and brain slices in an effort to use the data to develop a realistic mathematical model of tissues. Additionally we began preliminary studies examining the effects of a variety of perturbations on single cells, blood cell ghosts and brain slices. In this renewal we implement newly developed models that will enable the determination of the temperature dependance of the MR signals; for this purpose we have developed the cultured brain slice, developed methods to exmaine the dependance of MR signals on tissue heterogeneity, and a technique to examine single neurons at lower temperatures. With these methods our original aims can be fully realised. We believe that a thorough understanding of the signal characteristics of single cells and brain slices will lead to an improved understanding of the signal changes observed in MRI, which in turn may help develop a more quantitative approach to clinical MRI. This is especially important now that multicomponent ADCs, using long diffusion times, have been measured in humans, providing a compelling need for the studies in this proposal. The new understanding will ultimately improve the diagnostic sensitivity and specificity of MRI. Public Health: Stroke remains a major cause of morbidity in the world. The goal of this study is to understand the fundemental origin of signal changes seen in MRI of stroke, so that diagnosis and treatment of stroke may be improved. The methods will also have a broader application to other brain disorders and other diseases such as cancer and cardiac ischemia. PERFORMANCE SITE ========================================Section End===========================================
| Flint, Jeremy J; Hansen, Brian; Fey, Michael et al. (2010) Cellular-level diffusion tensor microscopy and fiber tracking in mammalian nervous tissue with direct histological correlation. Neuroimage 52:556-61 |
| Maly, Thorsten; Andreas, Loren B; Smith, Albert A et al. (2010) 2H-DNP-enhanced 2H-13C solid-state NMR correlation spectroscopy. Phys Chem Chem Phys 12:5872-8 |
| Shepherd, Timothy M; Thelwall, Peter E; Stanisz, Greg J et al. (2009) Aldehyde fixative solutions alter the water relaxation and diffusion properties of nervous tissue. Magn Reson Med 62:26-34 |
| Flint, Jeremy; Hansen, Brian; Vestergaard-Poulsen, Peter et al. (2009) Diffusion weighted magnetic resonance imaging of neuronal activity in the hippocampal slice model. Neuroimage 46:411-8 |
| Maly, Thorsten; Debelouchina, Galia T; Bajaj, Vikram S et al. (2008) Dynamic nuclear polarization at high magnetic fields. J Chem Phys 128:052211 |
