The desire to understand complex mental processes using functional MRI drives development of imaging techniques that scan the whole human brain at a high spatial and temporal resolution. In this work, an accelerated multishot three-dimensional echo-planar imaging sequence is proposed to increase the temporal resolution of these studies. A combination of two modern acceleration techniques, UNFOLD and GRAPPA is used in the secondary phase encoding direction to reduce the scan time effectively. The sequence (repetition time of 1.02 s) was compared with standard two-dimensional echo-planar imaging (3 s) and multishot three-dimensional echo-planar imaging (3 s) sequences with both block design and event-related functional MRI paradigms. With the same experimental setup and imaging time, the temporal resolution improvement with our sequence yields similar activation regions in the block design functional MRI paradigm with slightly increased t-scores. Moreover, additional information on the timing of rapid dynamic changes was extracted from accelerated images for the case of the event related complex mental paradigm.

Awake animal imaging is becoming an important tool in behavioral neuroscience and preclinical drug discovery. Non-invasive ultra-high-field, functional magnetic resonance imaging (fMRI) provides a window to the mind, making it possible to image changes in brain activity across distributed, integrated neural circuits with high temporal and spatial resolution. In theory, changes in brain function, anatomy, and chemistry can be recorded in the same animal from early life into old age under stable or changing environmental conditions. This prospective capability of animal imaging to follow changes in brain neurobiology after genetic or environmental insult has great value to the fields of psychiatry and neurology and probably stands as the key advantage of MRI over other methods in the neuroscience toolbox. In addition, awake animal imaging offers the ability to record signal changes across the entire brain in seconds. When combined with the use of 3D segmented, annotated, brain atlases, and computational analysis, it is possible to reconstruct distributed, integrated neural circuits or 'fingerprints' of brain activity. These fingerprints can be used to characterize the activity and function of new psychotherapeutics in preclinical development and to study the neurobiology of integrated neural circuits controlling cognition and emotion. In this review, we describe the methods used to image awake animals and the recent advances in the radiofrequency electronics, pulse sequences, and the development of 3D segmented atlases and software for image analysis. Results from pharmacological MRI studies and from studies using provocation paradigms to elicit emotional responses are provided as a small sample of the number of different applications possible with awake animal imaging.

The problem of k-space sample density compensation is restated as the normalization of the independent information that can be expressed by the ensemble of Fourier basis functions corresponding to the trajectory. Specifically, multiple samples (complex exponential functions) may be contributing to each independent information element (independent basis function). Normalization can be accomplished by solving a linear system based on the cross-correlation matrix of the underlying Fourier basis functions. The solution to this system is straightforward and can be obtained without resorting to discretization since the cross-correlations of Fourier basis functions are analytically known. Furthermore, no restrictions are placed on the k-space trajectory and its point-spread function. Additionally, the linear system can be used to elucidate key trade-offs involved in k-space trajectory design. The approach can be used to compensate samples acquired for image reconstruction or designed for low flip angle radiofrequency (RF) excitation. Here it is demonstrated for the latter application, using reversed spiral trajectories. In this case the linear system approach enables one to easily incorporate additional constraints such as smoothness to the solution. For typical RF excitation durations (<20 ms) it is shown that density compensation can even be achieved without numerical iteration.