Sub-second MRI has enhanced our understanding of brain structure and function in normal and disease states. Functional MRI studies of cerebral activation have better spatial and temporal resolution than positron emission tomography (PET). For detection of brain disease, MR diffusion and perfusion imaging serve as sensitive indicators of hyperacute stroke. These applications differ markedly yet share a common theme, they benefit from sub-second MRI. The most widely used approach to sub-second MRI, echo planar imaging (EPI), suffers from severe limitations. EPI shows artifacts, distortions and blurring, with complete brain signal loss near bone/air interfaces. Futhermore, rapid signal decay during EPI data acquisition limits spatial resolution and signal-to-noise ratio (SNR). These limitations become more severe with stronger magnetic fields, desirable for improving MR functional image contrast and signal strength. In this proposal, novel sub-second MRI technology will be developed and will overcome the limitations of three-dimensional (3D) EPI. Without major distortions or signal loss artifacts, this new technology will image the entire brain in a fraction of a second. These advances will be applied at high field strength to study the recently discovered "fast response" in the functional MR signal time course. This new 3D imaging technology will move MRI brain activation studies much closer to the temporal resolution of magnetoencephalography (MEG) which is limited in spatial resolution and localization. Specific aims: 1) To develop single-shot 3D gradient-and-spin echo (GRASE) technique. The following aims are to achieve interchangable improvements in SNR, resolution and data acquisition speed in sub-second images: 2) to implement variable signal encoding time (VET) in 2D and 3D single-shot sequences, 3) to encode k-space more efficiently using cylindrical and spherical coverage and 4) to optimize and test the new pulse sequence techniques with high performance gradient hardware specifically designed for brain imaging. The methods detailed in this proposal will speed the transformation of MRI from a static, two-dimensional diagnostic imaging modality to a dynamic four-dimensional brain probe, with time the fourth dimension. Ultimately, the tools developed herein will allow more detailed study of brain structure, function and dynamic physiology.