Human Brain Mapping of the Apparent Diffusion Coefficient (ADC) During Sleep and Wakefulness
Condition: Brain Mapping
Study type: Interventional
Phase: Early Phase 1

Summary: 
      Background:

      - The glymphatic system helps keep harmful waste from building up in the brain. Researchers
      think it is more active in people during sleep than while awake. They want to study the
      glymphatic system using magnetic resonance imaging (MRI).

      Objective:

      - To see if there are differences in the way waste is removed from the brain while a person
      is sleeping versus awake.

      Eligibility:

      - Healthy people age 18-60.

      Design:

        -  This study is in 2 parts.

        -  For the technical part (discontinued), participants will be screened with medical
           history and physical exam. They will have urine and breath alcohol tests.

        -  Participants will have 2 MRI scans. Before the scans, they will have urine and breath
           alcohol tests, and complete a questionnaire.

        -  For MRI, participants will lie on a table that slides in and out of a metal cylinder. A
           device will be placed over their head. They will lie still for up to 20 minutes at a
           time. They may be asked to stay awake or fall asleep for up to 2 hours at a time.

        -  For the research part, participants will be screened with medical history and physical
           exam. They will have urine and breath alcohol tests. For 1 week they will wear a device
           that monitors their activity and sleep.

        -  Participants will stay at NIH overnight. They will give a blood sample, have urine and
           breath alcohol tests, and complete a questionnaire.

        -  Participants will take memory, concentration, and thinking tests.

        -  Participants will have 3 MRI scans. An electroencephalography machine will record their
           brain activity. Electrodes will be placed on their scalp.
    

Detailed description: 
      OBJECTIVES:

      The primary objectives are to assess if there is an increase in the apparent diffusion
      coefficient (ADC) in the human brain during sleep when compared to the awake state and to
      determine if they vary across brain regions. Secondary outcomes are to assess inter subject
      variability in the differences in ADC between awake and sleep. We will also run exploratory
      analysis to determine if ADC changes with sleep are associated with subjective perception of
      rested sleep and to assess if there are differences in T1 in CSF between the scan taken prior
      to falling asleep and those taken shortly after waking up.

      STUDY POPULATION:

      Healthy adults. Males and females will be included.

      DESIGN:

      Observational study with a technical phase and two research phases.

        -  The technical phase (discontinued) will recruit controls in order to define best MR
           parameters and pulse sequence to be used for optimal ADC signal detection for which we
           request permission to recruit up to 20 healthy volunteers. Technical Developmental
           Phase: Each participant will have a set of MRI scans at the following two times of day:
           the 1st between 11:00 AM and 1:00 PM (noon) and the second between 6:00 PM and 8:00 PM
           (evening).

        -  Research Phase I (complete testing in 10 healthy controls to assess effects on
           wake/sleep states on whole brain ADC) and research Phase II (complete testing in a total
           of 30 subjects to assess if there are regional differences) and to address the main and
           secondary outcomes proposed above. Only if we show that ADC significantly changes during
           sleep compared to awake state will we proceed to phase II. For phases I and II, the
           participants will spend 3 night in the clinical center and will undergo two MRI scan
           sessions following two fo the night stays to quantify brain ADC; once while awake
           (following a night of sleep) and the other while asleep (following a night of sleep
           deprivation). Scans for both days will be performed in the morning (between 9-12 PM).
           Electrocardiogram (ECG) will be recorded during all MRI scanning procedures to monitor
           sleep. For the first of the three nights we will simultaneously record the
           electroencephalogram (EEG) and ECG on the participants while they sleep which will allow
           us to correlate the ECG to their EEG signal, which is the gold standard for measuring
           sleep.

      OUTCOME PARAMETERS:

      ADCs and ECG will be measured at each time point for each study participant (pertinent to
      research phase only).
    

Intervention name(s): Brain connectivity and physiology; Brain Wave
Intervention type(s): Other; Other
Intervention description(s): Two MRI scanning session will be obtained for each participant both at the same time of day (9AM 12 PM). In one occasion they will be scanned after a night of rested sleep while awake and on another day they will be scanned after one night of sleep deprivation while sleeping in the scanner. In addition to the most sensitive technique selected in the development phase (either DWI or MT), each imaging MRI session will include (1) a resting-state functional connectivity (RSFC; 10 minutes) scan using single-shot T2*-weighted EPI; and (2) quantitative T1 relaxometry (T1) in a CSF voxel (1mL; cubic) using an inversion recovery experiment with increased interpulse intervals (TI = 200, 300, 400, 500, 700, 1000, 1500, 2000, 3000, 5000, 10000 ms) and a long TR (10000 ms; scan time 2 min) to assess the level of solutes in CSF.; ECG will be used to monitor heart rate variability (HRV), which differ significantly between the waking state and the different sleep stages
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Human Brain; Sleep; EEG; Magnetic Resonance Imaging (MRI); Apparent Diffusion Coefficient (ADC)