Psychiatric illness

Major depressive disorder (MDD) affects 6.9 % of the U.S. adult population and costs an estimated $104 billion per year. Despite this tremendous impact on society, the biological mechanisms of MDD are still poorly understood and consequently treatment options are limited and often ineffective. There is a clear need to establish the abnormalities in the regions and circuits of the brain associated with MDD in order to enable the development of more effective, biologically targeted treatments. Magnetic Resonance Imaging (MRI) can be used to measure various properties of brain tissue, however, current MRI methods possess insufficient resolution and sensitivity to capture many of the subtle, yet critical, changes that can serve as neurobiological markers for MDD. Ultrahigh field MRI scanners, such as those operating at 7 Tesla (7T), are now making it possible to noninvasively visualize smaller, more subtle abnormalities in human brain structure and metabolism. While 7T scanners are more able to detect fine changes in brain tissue than conventional lower-field scanners, there are several physical limitations and technical issues that prevent the benefits offered at 7T from being fully exploited. In this proposal, the goal is to overcome these limitations with the development of specialized MRI pulse sequences and novel radiofrequency (RF) pulses. From these technical developments a comprehensive, multimodal 7T MRI protocol will be built that can be used to establish imaging biomarkers for MDD. Specifically, the aims of this proposal are: 1) To develop high-resolution 7T structural, diffusion and spectroscopic imaging methods to reveal grey matter abnormalities, white matter degradation and cellular loss associated with MDD and 2) To build a multiparametric 7T imaging protocol and apply it to compare quantitative imaging measures between a group MDD patients and controls. The design goal for the proposed 7T imaging sequences is to achieve 20–40% greater signal-to-noise ratio in important brain regions, while remaining within safety limits. The hypothesis is that the high-resolution, multimodal imaging data obtained utilizing these methods will reveal grey matter volume reduction, white matter degradation and neuronal and glial loss in substructures of the hippocampus and medial prefrontal cortex in MDD patients when compared to healthy controls. These quantitative imaging biomarkers for MDD will have significant value in noninvasively assessing treatment response and tailoring new therapies based on the fundamental underlying biology of MDD. This will ultimately lead to the development of more targeted and effective treatments for MDD, enhancing the quality of life of the millions of people who suffer from this disabling disease. Furthermore, because they are developed to address fundamental problems in 7T imaging, the tools produced in this study will be generally applicable to high-field MRI imaging of the brain, and so could be used to improve diagnosis, treatment and neurosurgical planning for a wide range of other neurological diseases.