Depression (target disease of this proposal) affects 34 million Americans including 2 million seniors per year. It is a leading cause of morbidity and mortality in older adults (target population of this proposal). The vascular depression hypothesis (proposed in 1998) remains the most salient theory explaining the onset and perpetuation of depression in older adults. This model is based on the observation that in older adults, white matter hyperintensities (a hallmark of small vessel disease, SVD) are associated with depression onset and perpetuation. Progress in understanding the relationship of small vessel disease with late-life depression has been stymied in part by lack of specificity of white matter hyperintensities which can represent components of edema, gliosis, ischemia, and inflammation. Traditional MR imaging is unable to distinguish between these components, and thus the specific mechanisms that contribute to depression remain unclear. The emergence of ultrahigh field MR imaging allows for greater specificity of the WMH lesions, and other components of small vessel disease. Bringing 7 tesla (T) imaging into mainstream clinical use will be accomplished through 1) having exclusive (over 1.5/3T) application(s) and 2) achieving robust, safe, consistent, and homogenous high-quality images. Through a consortium consisting of experts at University of Pittsburgh combined with collaboration at FDA, University of Minnesota, and Quality Electrodynamics Inc., our goal is to enhance our understanding of the neuropathophysiology, treatment, and management of depression in older adults. We will achieve this goal through the development of robust radiofrequency methodology, as well as pulse sequences that produce 7T images with the aforementioned necessary attributes. This will be paired with complementary 3T MRI at baseline. We will use our recently developed (as well as a proposed) custom designed 7T radiofrequency coil system and pulse sequences that are already being used in disease/patient studies. Based on our preliminary results, the proposed RF solution will provide unprecedented homogeneity and consistency among different subjects/patients, and therefore excellent signal to noise ratio and contrast to noise ratio for detection of components of small vessel disease. The study will examine two cohorts 1) a group of 30 older adults recruited through the Alzheimer's Disease Research Center (ADRC) for developing an MRI to histopathology statistical model of SVD and 2) 60 older adults with late-life depression who will undergo scanning at baseline and after 2 years. The longitudinal 7T MRI and SVD model will be used to help characterize the small vessel changes associated with depression in older adults. In summary, this study develops an emerging and timely technology (high-performance ultrahigh field MRI) to study a critical pathophysiological process (cerebral small vessel disease) in a clinically relevant population (Late-Life Depression). This project will further advance all of these three domains.
The overall objective of this proposal is to enhance our understanding of the neuropathophysiology, treatment, and management of depression in older adults. This will be accomplished through the development of radiofrequency hardware, methodology, pulse sequences and protocols using 7 Tesla (T) human magnetic resonance imaging (MRI) in conjunction with complimentary 3T MRI. The clinical relevance of the proposed tools will be achieved through comprehensive characterization of 1) components of cerebral small vessel disease in individuals with late-life depression and 2) progression of small vessel disease markers over 2 years. One of our overarching goals is to achieve a highly useful 7T clinical utility, which requires high quality, robust, and consistent acquisitions. This could be a potentially exclusive (over other human MRI field strengths) application for 7T imaging.
| Smagula, Stephen F; Karim, Helmet T; Rangarajan, Anusha et al. (2018) Association of Hippocampal Substructure Resting-State Functional Connectivity with Memory Performance in Older Adults. Am J Geriatr Psychiatry 26:690-699 |
| Santini, Tales; Kim, Junghwan; Wood, Sossena et al. (2018) A new RF transmit coil for foot and ankle imaging at 7T MRI. Magn Reson Imaging 45:1-6 |
| Wood, Sossena; Krishnamurthy, Narayanan; Santini, Tales et al. (2017) Design and fabrication of a realistic anthropomorphic heterogeneous head phantom for MR purposes. PLoS One 12:e0183168 |
