PET Imaging in Chronic Traumatic Encephalopathy
Condition: Brain Disease; Brain Mapping
MeSH terms: Brain Diseases; Brain Injuries, Traumatic; Chronic Traumatic Encephalopathy
Study type: Observational

Summary: 
      Background:

      - Chronic traumatic encephalopathy (CTE) is a brain disease caused in part by head injury.
      The brain changes from CTE can only be seen at autopsy. Researchers want to test a new brain
      scan to help diagnose CTE in living patients.

      Objective:

      - To determine if a new type of brain scan can detect changes that occur in chronic traumatic
      encephalopathy.

      Eligibility:

      - Adults age 18 60 with previous head injury or participation in certain sports.

      Design:

        -  Participants will be screened with:

        -  Physical exam

        -  Blood and urine tests

        -  Tests of thinking, mood, and memory

        -  30-minute magnetic resonance imaging (MRI) brain scan. A magnetic field and radio waves
           take pictures of the brain. Participants will lie on a table that slides into a metal
           cylinder. They will get earplugs for the loud knocking sounds.

        -  Visit 1: Participants will have a 70-minute PET scan of the brain with a small amount of
           a radioactive chemical. That will be injected through an intravenous tube (catheter) in
           each arm. A catheter will also be put into an artery at the wrist or elbow.

        -  Participants will lie on a bed that slides in and out of a donut-shaped scanner. A
           plastic mask may be molded to their face and head. Vital signs and heart activity will
           be checked before and during the scan.

        -  Blood and urine will be taken before and after the scan.

        -  Participants will be checked on by phone the next day.

        -  Visit 2: Participants will repeat Visit 1 with a different chemical and no artery
           catheter.

        -  Visit 3: Participants may have a spinal tap. Some fluid will be removed by needle
           between the bones in the back.
    

Detailed description: 
      Objective: To determine if the PET radioligand [11C]PBB3 can detect aggregates of tau protein
      in the brains of patients with history of traumatic brain injury (TBI) and suspected chronic
      traumatic encephalopathy (CTE).

      Study population: The proposed study will include 40 subjects. Twenty will be patients with
      history of TBI and suspected CTE and 20 will be healthy cognitively normal volunteers without
      history of TBI.

      Design: Subjects will undergo medical screening and have brain MRI and neuropsychological
      testing performed. Subjects will undergo one brain PET scan with [11C]PBB3 to detect
      aggregates of tau protein. Subjects will also have one brain PET scan with [11C]Pittsburgh
      compound B (PIB) to detect amyloid plaques. Subjects will be asked to have a lumbar puncture
      to measure CSF tau concentrations.

      Outcome measures: The primary outcome measure will be the amount of [11C]PBB3 binding in the
      brain. We will quantify the radioligand s brain uptake, washout, plasma clearance, and
      distribution volume using compartmental modeling. Distribution volume of [11C]PBB3 is
      proportional to the density of insoluble paired helical filaments of tau and is equal to the
      ratio at equilibrium of uptake in brain to the concentration of parent radiotracer in plasma.
      As an exploratory measure, we will determine if there is a relationship between [11C]PBB3
      binding in brain and gray matter loss on MRI. We will also measure the amount of [11C]PIB
      binding in the brain using the Logan reference tissue method with cerebellum as reference.
    

Observational model: Cohort
Time perspective: Prospective
Keywords: Encephalopathy; Imaging Studies; Dementia; Cerebellar Cortical Atrophy