Project 3 of the PPG grant "Stress and Atherosclerotic Plaque Macrophages A Systems Biology Approach," funded by the NHLBI, examines the relationship between psychosocial stress and atherosclerotic inflammation, cell proliferation and burden using novel PET/MRI. Individuals with post-traumatic stress disorder, trauma controls and healthy controls will be recruited into a two-center clinical study. The study team will use functional MRI to examine the relationship between activation of fear circuits in the brain and relate these data to hematopoietic system activation, and vascular inflammation measured by FDG-PET, and atherosclerotic burden measured by MRI.
In Project 3, the study team will employ innovative PET combined with magnetic resonance imaging (PET/MRI) to simultaneously study the hematopoietic system, the artery wall, and the brain's fear system, which comprises the amygdala and anterior cingulate cortex (ACC), to elucidate the relationship between psychosocial stress and systemic inflammation/atherosclerosis in a two center clinical study looking at: I) individuals with PTSD, II) individuals without PTSD but with exposure to severe psychosocial trauma (Trauma Control), and III) matched volunteers with neither PTSD nor exposure to trauma (Healthy Control). Participants in the three study groups, recruited from urban settings in New York and Boston, will be group-matched by age, gender, and Framingham risk scores (FRS). The study team will recruit 80 subjects in each group and in Aim 1, investigate the relationship between PTSD and atherosclerotic inflammation and burden measured by PET/MRI. In Aim 2, the study team will examine the relationships between brain's fear circuit responsiveness to threat assessed by functional MRI (fMRI) and white matter integrity assessed by diffusion tensor imaging (DTI) and relate these data to hematopoietic system activation, and vascular inflammation measured by fluorodeoxyglucose (FDG)-PET and atherosclerotic burden measured by MRI. The following will occur during the imaging visit: 1. Questionnaire: study staff will administer a standardized questionnaire to collect general information on age, gender, race, and current contact information. A PET/MRI pre-screening form will also be administered to confirm eligibility for the PET/MRI scan. This questionnaire is specific to the PET/MRI scan. 2. Blood pressure: One blood pressure reading, taken in the dominant arm, will be performed per the American Heart Association recommendations. 3. Anthropometrics: Body weight and height will be measured according to standard methods and body mass index will be calculated as an index for obesity. Waist circumference will also be measured. 4. Blood draw: approximately 3 tablespoons of blood will be drawn to evaluate clinical variables. 5. Imaging at Mount Sinai or Massachusetts General Hospital: A Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) scan 6. Urine drug screen 7. C-SSRS safety assessment
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
190
Innovative PET combined with magnetic resonance imaging (PET/MRI) to simultaneously study the hematopoietic system, the artery wall, and the brain's fear system, which comprises the amygdala and anterior cingulate cortex (ACC)
Massachusetts General Hospital
Boston, Massachusetts, United States
Icahn School of Medicine at Mount Sinai
New York, New York, United States
Atherosclerotic burden in PTSD using PET/MRI
The atherosclerosis burden as measured by 18F-FDG-PET/MRI
Time frame: Day 1
Degree of brain fear circuit activation
The degree of brain fear circuit activation (both at rest and in response to validated stimuli) to be associated with activation of hematopoietic organs 18F-FDG PET imaging.
Time frame: Day 1
Level of circulating HPSCs
Time frame: Day 1
Level of circulating immune cells
Time frame: Day 1
Level of soluble inflammation biomarkers
Time frame: Day 1
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