All the 7 Tesla imaging studies are performed using the Tic Tac Toe RF Coil System (16 transmit channels and 32 receive channels). The transmit channels are combined to operate in the single transmit mode of the MRI system; no adjustments are needed between subjects.
IMAGING ADVANCEMENTS IN SMALL VESSEL AND CSF FLOW PATHOPHYSIOLOGY OF PRE-CLINICAL ALZHEIMER’S DISEASE
Narrative: The overall objective of this proposal is to further enhance our understanding of small vessel disease (SVD) and its relation to pre-clinical Alzheimer’s disease (AD) using advancements in 7T human MRI. This proposed interdisciplinary project aims to develop advanced MR methods (hardware, acquisition, analysis) with 7T human imaging -recently FDA-approved- and study the pathways linking small vessel and CSF flow pathophysiology to AD. It will be achieved through a consortium consisting of expertise at 1) U. of Pittsburgh (Pitt) -MRI acquisition and analysis-, and AD; 2) FDA -RF-heating matters in relation guidelines-; 3) U. of Minnesota (UMN) -MRI acquisition-; 4) Quality Electrodynamics Inc. (QED) -integration of patient friendly hardware-; and Montreal Neurological Institute (neuro) -MRI analysis-. We will examine small vessel morphology, cerebrovascular reactivity (CVR), and CSF flow, all of which are inter-related components in AD pathophysiology.
Funding Agency: NIH R01 AG063525
METABOLIC AND INFLAMMATORY PATHWAYS OF MIDLIFE NEUROCOGNITIVE DISPARITIES
Narrative: As the US population ages, cognitive impairment is becoming a rising and intractable problem, particularly for individuals at relative socioeconomic disadvantage who are at increased risk for premature neurocognitive aging and dementia. The public health implications of the proposed research include the potential to identify modifiable risk factors that track a socioeconomic gradient and predict preclinical cognitive decline across mid-life, a period when differential trajectories of cognitive aging begin. The project focus is on metabolic risk factors that associate with disadvantage and may accelerate preclinical brain aging investigated using 7 Tesla neuroimaging and cognitive decline.
Funding Agency: NIH 5R01DK110041
EVALUATION OF BRAIN AND COGNITIVE CHANGES IN OLDER ADULTS WITH MCI TAKING LITHIUM TO PREVENT ALZHEIMER TYPE DEMENTIA
Narrative: Alzheimer’s disease (AD) is the most common cause of dementia in adults 65 years and older. AD leads to a complete loss of memory and independent function, and, presently, there is no cure. Many studies suggest that lithium treatment may delay dementia onset or slow its progression. However, more research is needed to understand the extent of its anti-dementia properties, as well as its safety, if it will be deployed broadly in the general population. This study using 7 Tesla neuroimaging examines whether lithium has anti- dementia properties in older adults who have mild cognitive impairment and are at risk of becoming demented.
Funding Agency: NIH 3R01AG055389
DEPRESSION IN DEMENTIA CAREGIVERS
Narrative: Late-life depression (LLD) impairs quality of life and has serious health consequences that disproportionately affect certain sub-groups of older adults, including informal providers of dementia care. In this K01 application we test and refine a model of LLD pathogenesis using 7 Tesla neuroimaging in dementia caregivers that posits sleep- wake activity disruption contributes to accelerated brain structural aging, which in turn, affects the key structural networks (executive and central visceral control) that underlie LLD risk. This generate evidence regarding the specific alterations to brain structure connectivity, and behavioral drivers of these changes, which increase LLD vulnerability and thereby represent targets for deficit-based LLD prevention strategies.
Funding Agency: NIH 5K01MH112683
NEURAL MECHANISMS OF MONOAMINERGIC ENGAGEMENT IN LATE LIFE DEPRESSION TREATMENT RESPONSE (NEMO)
Narrative: This is a 7 Tesla neuroimaging study that tests a mechanistic model describing the treatment-related dynamic changes of the core cognitive and affective networks at rest and during standard behavioral tasks. The results will further our understanding about the neural systems changes associated with pharmacotherapy in late-life depression.
Funding Agency: NIH 5R01MH076079
DIMENSIONAL OUTCOMES AND NEURAL CIRCUITRY ASSOCIATED WITH PSYCHOSIS RISK
Narrative: Schizophrenia is a chronic debilitating disorder with poor long term outcome. Predicting the onset of psychosis, early detection and intervention can reduce long term morbidity of the illness. Moreover, predicting the onset of psychosis along with a broad spectrum psychopathology related to psychosis is equally important because of significant morbidity associated with such sub-clinical symptoms. Even individuals with sub-clinical symptoms demonstrate significant social function deficits that increases the cost of caring for these individuals. Since using DSM-defined disorders do not carry the same biological connotation as other medical disorders, using biologically-based dimensional measures such as that attained with 7T neuroimaging to characterize dimensional predictors of risk for psychosis and broad psychosis spectrum psychopathology may be more important to develop reliable tests to predict psychosis and design novel interventions. This project focuses on developing these measures.
Funding Agency: NIH 5R01MH112584
HIGH PERFORMANCE IMAGING FOR ASSESSMENT OF SMALL VESSEL DISEASE IN OLDER ADULTS WITH DEPRESSION
Narrative: The overall objective of this proposal is to enhance our understanding of the neuropathophysiology, treatment, and management of depression in older adults. This is accomplished through the development of radiofrequency hardware, methodology, pulse sequences and protocols using 7T 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 develop and 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.
Funding Agency: NIH 5R01MH111265
NEUROVASCULAR DETERMINANTS OF COGNITIVE FUNCTION IN ADULTS WITH SICKLE CELL DISEASE
Narrative: Cognitive impairment is a poorly understood, serious, and emerging complication for adult patients with sickle cell disease. Because there is extensive microvascular damage from oxidative damage in sickle cell disease, we hypothesize that this is also present in the cerebral microvasculature to cause cognitive impairment. In this project, we test this hypothesis by correlating markers of inflammation and oxidative damage with cognitive performance and 7T brain MRI microvascular findings in these patients. Our long term goal of this project is understanding the mechanisms and risk factors of cognitive impairment in sickle cell disease.
Funding Agency: NIH 5R01HL127107
HIGH PERFORMANCE IMAGING FOR ASSESSMENT OF SMALL VESSEL DISEASE IN OLDER ADULTS WITH DEPRESSION (SUPPLEMENT FOCUSED on AD and AD RELATED PATHOLOGY)
Narrative: Alzheimer’s Disease (AD) and late life depression (LLD) commonly co-occur, for reasons not yet understood. It has been suggested that small vessel disease is a shared mechanism leading to both AD and LLD. Our parent R01MH111265 project focuses on small vessel disease pathogenesis of LLD. This projects aims at leveraging our ongoing 7T imaging developments and applications in LLD and extending it to the vascular pathogenesis of AD using 7T in-vivo and ex-vivo imaging.
Funding Agency: NIH 5R01MH111265 Supplement
BEHAVIORAL MECHANISMS LINKING PERSONALITY TO HEALTH IN MIDLIFE
Narrative: The objective of this research program is to identify biobehavioral pathways by which certain dimensions of personality and other psychosocial attributes confer risk or afford protection against midlife changes in biological and functional capacities germane to aging, including the progression cardiometabolic risk, cognitive functioning, physical functioning, and aspects of cellular aging. The current NIA project (RO1 AG056043) supports the ~16 year follow-up (wave 2) of 650 men and women first evaluated in 2001-2005 (wave 1) as participants of the Adult Health and Behavior –Phase 1 (AHAB1) project, an institutional resource for the study of individual differences. The goal of this work is to extend wave 2 measurements to newly obtain high-resolution (7 Tesla) human brain imaging data, thus expanding the scope of program outcomes in the cognitive domain to include preclinical changes in brain morphology, with the aim of identifying factors in midlife that modulate risk for later life dementia and dementia-related sequelae. A second objective is to enable complete harmonization and data aggregation between AHAB1 and AHAB2, a parallel longitudinal study of comparable sampling frame that is also currently in wave 2 of data collection (~10 year follow-up; RO1 DK110041). The wave 2 protocols including 7T neuroimaging for the two cohorts are now identical in all respects, with the sole exception that the acquisition of high-resolution brain imaging data proposed here is already a component of AHAB2.
Funding Agency: NIH 5R01AG056043 Supplement
AMYLOID PATHOLOGY AND COGNITION IN NORMAL ELDERLY
Narrative: Our field has recently initiated four NIH-funded trials aimed at the prevention of Alzheimer’s disease (AD) by targeting the amyloid-beta protein that is believed to start building up in the brains of many older adults as much as 10-15 years before any memory problems occur. However, we have no firm understanding of the time frame or risk of progression from this asymptomatic “amyloid-positive” state to the onset of memory problems and Alzheimer’s disease. Currently we are using state-of-the-art brain imaging including 7T human MRI and PET to continue the study of a group of older adults who have already been studied by us for up to 10 years to assess how the amyloid-positive state leads to the development of memory problems and Alzheimer’s disease, thus facilitating the interpretation of the ongoing prevention trials.
Funding Agency: NIH 2RF1AG025516
HIGH PERFORMANCE IMAGING FOR ASSESSMENT OF SMALL VESSEL DISEASE IN OLDER ADULTS WITH DEPRESSION (SUPPLEMENT FOCUSED PRE-DOC TRAINING in RESTING STATE fMRI and RF COIL DESIGN)
Narrative: The parent research proposal largely uses the progress in 7T RF hardware developments, pulse sequence and novel data analysis methods to construct a SVD prediction model. The potential statistical model can be used to predict and study the progress of SVD and its relation to the LLD. The SVD model, as it stands, is created from only structural (neuroradiological) features. We hypothesis that adding 7T functional imaging component to the parent research proposal might provide either an independent predictor or an additional relevant functional feature that can be used in the predictive model of the parent grant. This new functional feature might add to the predictive power of the SVD model developed in specific aims of the parent grant.
Funding Agency: NIH 5R01MH111265 Supplement
INVESTIGATING THE LINK BETWEEN PRE-CLINICAL ALZHEIMER’S DISEASE AND POSTOPERATIVE COGNITIVE DYSFUNCTION USING FUNCTIONAL NEUROIMAGING
Narrative: The goal of this pilot project is to develop a 7T functional neuroimaging program of postoperative cognitive dysfunction.
Funding Agency: University of Pittsburgh Physicians Academic Foundation
ULTRA-HIGH-FIELD MAGNETIC RESONANCE IMAGING BIOMARKERS OF MULTIPLE SCLEROSIS
Narrative: The goal of this pilot project is to develop a 7T functional neuroimaging program of Multiple Sclerosis.
Funding Agency: University of Pittsburgh Physicians Academic Foundation