PET Imaging of DHA Metabolism
Condition: Healthy
Study type: Observational

Summary: 
      This study will examine the use of positron emission tomography (PET) for measuring
      docosahexaenoic acid (DHA) absorption from the blood into the brain. DHA is a type of fatty
      acid found in fish and other seafood. It is involved in brain cell activity that underlies
      the ability to think, move, and respond to the outside world. When the amount of DHA in the
      brain is low, the brain may not work the same as if there were a normal amount of DHA. If PET
      can be used successfully to evaluate brain DHA metabolism, this method might be useful for
      future studies of alcoholism, since brain DHA levels are influenced by alcohol consumption.

      Healthy normal volunteers between 18 and 65 years of age may be eligible for this study.
      Because study participants must stop taking any medications, including herbal preparations,
      individuals who require regular medication are excluded from this protocol. Participants will
      undergo the following tests and procedures:

        -  Psychological questionnaires concerning thoughts and behaviors.

        -  Nutritional status analysis: A dietitian will assess the subject's nutritional status
           through questionnaires and measurement of body fat. Body fat is measured using
           bioelectrical impedance analysis. This analysis uses a low, safe electric current to
           measure body composition, giving a reading of the percentage of fat in the body.

        -  Fat biopsy to measure the composition of fat tissue: An area on the upper half of the
           buttock will be numbed and a needle will be inserted to aspirate a sample of fat tissue
           for analysis.

        -  Blood drawing: Blood samples will be collected at the time of the fat biopsy and the PET
           scan (see below) to measure DHA and indicators that may influence DHA.

        -  Diet: 3 days before the fat biopsy and at least 3 days before the PET scan, subjects
           will consume a diet low in DHA and other omega-3 fats. This no seafood diet prohibits
           eating fish, shellfish, seaweed, seafood, health food products or supplemental vitamins,
           and foods containing canola or flaxseed oil. Caffeine-containing beverages are limited
           to one per day for 3 days before the study. Alcoholic beverages are prohibited for 2
           weeks before the study. For 24 hours before the PET scan, subjects eat only standard
           meals that will be provided to them.

        -  Magnetic resonance imaging: A brain MRI scan will be done to fit the PET scan images
           onto a picture of the whole brain. During the scan, the subject lies on a table inside a
           narrow metal cylinder containing a strong magnetic field.

        -  PET scan: Before the PET scan, catheters (small plastic tubes) are inserted into an arm
           vein and into a wrist artery. The venous catheter is used for injecting a radioactive
           substance that will be detected by the scanner, and the arterial catheter is used for
           collecting blood samples during the scan. For the scan, the subject lies on a bed that
           slides into the doughnut-shaped scanner. A mask is placed to keep the head still. A
           transmission scan is done to see how much radiation the skull absorbs. Radioactive water
           (15O-water) is then injected into the blood, and the brain is scanned for about 10
           minutes to measure brain blood flow. Then, radioactive DHA (11C-DHA) is injected,
           followed by about 1-1/2 hours of scanning to measure DHA absorption into the brain.
    

Detailed description: 
      Docosahexaenoic acid (DHA, 22:6 n-3) is an essential omega-3 fatty acid that is selectively
      concentrated in the brain. Epidemiologic studies suggest that DHA deficiency is related to
      affective disorders, while clinical studies suggest that DHA is efficacious in treating
      depression. DHA has also been shown to be an important second messenger involved in
      phospholipase A(2)-mediated signal transduction. Although animal studies have provided a
      wealth of knowledge about the role of DHA in neural function, no method exists of evaluating
      DHA content or metabolism in the living human brain. Our goal is to establish a quantitative
      method of examining brain DHA metabolism using PET in healthy humans and to measure regional
      DHA incorporation from plasma into the brain. Utilizing the data from the pilot phase with
      healthy volunteers, we will apply the method to study DHA metabolism in alcoholics. Since
      alcohol consumption depletes brain DHA, we hypothesize that compared to healthy volunteers;
      alcoholics will have a decreased rate of incorporation of DHA from plasma into brain.
      Utilizing the method we have established, we anticipate that we will find previously
      undetectable metabolic abnormalities in alcoholics. We may further find that such
      abnormalities are correlated with cognitive or behavioral function. Now that the pilot phase
      of the protocol has been completed, we are proceeding with the main phase of the protocol to
      study non-smoking chronic alcoholics.
    

Keywords: Positron Emission Tomography; Phospholipids; Alcoholism; [11C]Docosahexaenoate; [150]Water; Brain; Fatty Acids; Blood Flow; Healthy