The overarching goal of this study is to develop PET/MR techniques for the diagnosis of neuropsychiatric post-acute sequelae (PASC) of SARS-CoV-2. The central hypothesis is that immunological and cerebrovascular dysfunction after acute SARS-CoV-2 infections mediate neuropsychiatric PASC (NP-PASC).
Used to evaluate neuroinflammation and cerebrovascular measures. Some MRI image acquisitions will employ work in progress (WIP) sequences, including ASL (Arterial Spin Labeling), Diffusion and T2-weighted EPI (DT2W), Golden-angle radial sparse parallel (GRASP) DCE-MRI, and Magnetization Transfer (MT) imaging.
Eligibility
Sex: ALLMin age: 18 YearsMax age: 50 Years
Medical Language ↔ Plain English
Inclusion Criteria:
* Neuropsychiatric symptoms are defined as respectively a) objective cognitive dysfunction on bedside cognitive testing (ACE-III (Addenbrooke's Cognitive Examination III) =\< 86/100, at least 12th grade educational level), and/or b) anxiety, depression or psychotic illness as indicated by the DSM-5 diagnostic criteria, evaluated with the MINI (Mini International Psychiatric Interview) or SCID-5 (Structured Clinical Interview for DSM-5 Disorders, Research Version). It is expected some patients may fall into both categories (cognitive and psychiatric complications), in which case they will be included in this study.
* Infection with SARS-CoV-2 (3-12 months before study) will be verified based on positive PCR test results provided by the NYU EMR or subject records. Investigators will further record the clinical history and perform nucleoprotein- and spike-antibody testing. Anecdotal evidence shows that anti-nucleoprotein and anti-spike tests will be positive in individuals who had past SARS-CoV-2 infection, but only anti-spike tests will be positive in individuals who were vaccinated but did not have past infection, unless the infected individual has already lost the antibodies due to natural infection .
* Able to sign informed consent as evaluated by the UCSD Brief Assessment of Capacity to Consent (UBACC) test.
Subgroup Inclusion Criteria
* NP-PASC subjects will have new onset a) cognitive and/or b) psychiatric symptoms following SARS-CoV-2 infection.
* CC will have a history of SARS-CoV-2 infection but will not meet the criteria for any DSM-5 diagnosis and will perform within normal limits on cognitive tests.
Exclusion Criteria:
* If vaccinated for SARS-CoV-2, at least 3 months past the last vaccine administration.
* Subjects with suicidal ideation who require inpatient or intensive level of care, as determined by a study clinician (Dr. Frankle or Dr. Iosifescu) based on the answers to the screening interview. These patients will be immediately referred to appropriate clinical treatment.
* Pregnant women or those who become pregnant as determined by a urine test at the time of the blood test and on the day of the PET/MR scan.
* Obese individuals (BMI \>= 30) and individuals with cardiovascular risk factors (e.g., uncontrolled high blood pressure, hypercholesterolemia, current tobacco smokers or smoking in the last 12 months, diabetes mellitus).
* Individuals with history of serious or unstable medical illness associated with chronic inflammation other than PASC (e.g., rheumatoid arthritis, SLE, etc).
* Current traumatic brain injury. Subjects with a history of chronic pre-existing neurological disease (multiple sclerosis, degenerative disease such as ALS, Parkinson disease and any movement disorders, etc), i.e. neurological symptoms should be new onset for inclusion. Patients with substance use disorders, including alcohol, active within the last 12 months.
* Clinical or laboratory evidence of hypothyroidism. A thyroid stimulating hormone (TSH) test will be drawn in blood, and the patient will be excluded if TSH is abnormal.
* Patients who have had electroconvulsive therapy (ECT) within the 6 months preceding baseline.
* Subjects who had recently taken psychotropic medications will be scanned only after a period greater than five half-lives since the last dose of their psychotropic medication. Subjects who choose to start treatment (with psychotropic medication) for their symptoms immediately will thus be excluded.
* Contraindications to 3T whole body MRI scanners (e.g., pacemaker, cerebral aneurysm clip, cochlear implant, presence of shrapnel in strategic locations, metal in the eye, claustrophobia, or other problems).
* Contraindications for Gadolinium-based MRI contrast (allergies to contrast agents and kidney health)
* Recent exposure to radiation (i.e., PET from other research) which when combined with this study would be above the allowable limits of 5 rem per 12 months as confirmed by the Radiation safety questionnaire.
* If CSF sampling: contraindication for a lumbar puncture (i.e. intracranial mass, bleeding diathesis, spinal developmental anomalies, or local skin infection involving the lower back). Complete blood count and coagulation studies will be drawn, and if abnormal (INR\>1.3, platelets less than 100), subjects will be able to complete imaging studies but will not be eligible for the lumbar puncture procedure part of the study.
* Unable to sign informed consent or to comply with study assessments.
* Urine will be collected for toxicology screening (amphetamine, barbiturates, benzodiazepines, cocaine, methadone, opiates, phencyclidine/PCP, THC, and tricyclic antidepressants). Subjects in whom THC is found will be scanned only after abstaining for 7 days. A pregnancy test will be performed on all premenopausal women to ensure exclusion criteria are appropriately screened.
Locations (1)
NYU Langone Health
New York, New York, United States
Outcomes
Primary Outcomes
Level of Translocator Protein (TSPO)
Binding of PET tracer to TSPO.
Time frame: PET/MR Visit (Day 1)
Occurrence of Microhemorrhages
Evaluated using MRI images (Susceptibility Weighted MRI (SWI), Fluid Attenuated Inversion Recovery (FLAIR), Diffusion Weighted Imaging (DWI), and anatomical MRI).
Time frame: PET/MR Visit (Day 1)
Permeability Surface Area Product (PS)
Used to evaluate disruptions in the blood-brain-barrier. Derived from the DCE-MRI.
Time frame: PET/MR Visit (Day 1)
Cerebral Blood Flow
Evaluated using cerebral blood flow maps from Arterial Spin Labeling (ASL).
Time frame: PET/MR Visit (Day 1)
Peripheral Levels of Pro-Inflammatory Cytokines
Evaluated using blood samples.
Time frame: PET/MR Visit (Day 1)
Peripheral Levels of High-Sensitivity C-reactive Protein (hs-CRP)
Evaluated using blood samples.
Time frame: PET/MR Visit (Day 1)
CSF Levels of Pro-Inflammatory Cytokines
Evaluated using cerebrospinal fluid collection (optional procedure).
Time frame: CSF Visit (Screening) (Optional)
CSF Levels of High-Sensitivity C-reactive Protein (hs-CRP)
Evaluated using cerebrospinal fluid collection (optional procedure).