Julie C. Chapman, PsyD

1
Clinical and Advanced NeuroimagingA Primer for
Providers

• Julie C. Chapman, PsyD
• Director of Neuroscience
• War Related Illness Injury Study Center
• Veterans Affairs Medical Center
• Washington, DC
• Assistant Professor of Neurology
• Georgetown University School of Medicine

• Patrick Sullivan, MA
• Neuroimaging Lead, Chapman Laboratory
• War Related Illness and Injury Study Center
• Veterans Affairs Medical Center
• Washington, DC

2
Disclaimer

• The views expressed in this presentation are
  those of the author and DO NOT reflect the
  official policy of the
• Department of Veterans Affairs
• or
• the United States Government

3
What is Neuroimaging?

• Since we cannot generally take photographs of the
  brain in vivo, imaging technologies allow us to
  view the brain indirectly.

4
Neuroimaging in Clinical Practice

• Which professions utilize clinical neuroimaging?
• Radiology
• Neurology
• Psychiatry
• Physiatry
• Neuropsychology
• Neurosurgery

• What is clinical neuroimaging used to assess?
• Tumor
• Stroke
• Brain Injury
• Neurodegenerative disease

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Neuroimaging Methods Conventional vs. Advanced

• Conventional

• Brain scans used in clinical practice.
• X-ray (Skull films)
• Computed Tomography (CT) often used to image
  acute conditions
• Magnetic Resonance Imaging (MRI)
• Nuclear Medicine
• Positron Emission Tomography (PET) Used often by
  Oncology and Cardiology for clinical purposes

6
Neuroimaging Methods Conventional vs. Advanced

• Advanced

• Experimental brain scans used in research
• (Sometimes used clinically by Neurosurgeons)
• Advanced Magnetic Resonance Imaging (MRI)
  include
• Diffusion Tensor Imaging (DTI)
• functional Magnetic Resonance Imaging (fMRI)
• Nuclear Medicine (Research Clinical)
• Positron Emission Tomography (PET) (brain)
• Single-Photon Emission Computed Tomography
  (SPECT)

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Structural vs. Functional Neuroimaging Methods

• Structural Methods

• Functional Methods

• Examine brain anatomy (brain structures)
• X-ray
• Computed Tomography (CT)
• Magnetic Resonance Imaging (MRI)
• Clinical scans
• DTI

• Examine brain function (brain in action)
• Functional Magnetic Resonance Imaging (fMRI)
• Positron Emission Tomography (PET)
• Single-Photon Emission Computed Tomography (SPECT)

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Ionizing Radiation

• Radiation with enough energy
• to remove an electron from an atom or molecule
• Exposure to ionizing radiation causes damage to
  tissues, can result in mutation, can contribute
  to cancer.
• Lifetime exposure limits
• X-ray/Computed Tomography Ionizing Radiation
• PET/SPECT Ionizing Radiation
• MRI NON-ionizing Radiation

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Structural Imaging Methods
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X-Rays

• Ionizing Radiation
• Measures density of tissue
• Used to take one-view pictures
• Limitations
• Resolution (spatial) ability to distinguish
  changes in image across different spatial
  locations.
• Contrast intensity differences

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Computed Tomography (CT)

• Ionizing Radiation
• CT uses an x-ray that moves around
• body/brain to create a 3-dimensional map.
• Uses a computer to integrate information
• Can distinguish between gray/white matter and CSF
• Limitations
• Resolution (spatial) ability to distinguish
  changes in image across different spatial
  locations.
• Contrast intensity differences

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Magnetic Resonance Imaging MRI

• MRI Benefits over X-ray CT scans
• Non-ionizing radiation
• Better resolution
• Better contrast

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MRI How is the picture made?

• How do we get from magnet to image?

Image from Chapman Lab WRIISC-DC
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Magnetic Resonance Imaging Components
Diagram from Magnet Lab Florida State University
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Magnetic Resonance ImagingThe Basics

• Magnetic
• The scanner has a powerful magnet that is always
  on
• This magnet produces a constant and very large
  electromagnetic current Static Magnetic Field
• Outside the scanner, atomic nuclei in the brain
  (or body) spin randomly
• Once inside the scanner, these nuclei align their
  spins in the direction of the static magnetic
  field

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MRI Pulse Sequences

• A pulse sequence is a group of computerized
  instructions that command the scanner hardware to
  emit a brief series of radiofrequency waves (and
  activate the gradient coils)
• The pulse sequence is geared to the resonant
  frequency of atomic nuclei in the brain (or
  body).

Images from Chapman Lab WRIISC-DC
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Magnetic Resonance ImagingThe Basics

• Resonance Radiofrequency coils turn on only
  during image acquisition
• Radiofrequency coils transmit the pulse sequence
  (brief series of radiofrequency RF waves).
  These waves PERTURB the alignment of nuclei with
  the static magnetic field.
• The pulse sequences are geared to the resonant
  frequencies of the nuclei. Different tissue types
  respond uniquely to these disruptions allowing us
  to differentiate between tissues.
• Eventually the nuclei return to their alignment
  with the static magnet field and as they do, they
  give off the MR signal which is received by the
  RF coils.

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Magnetic Resonance ImagingThe Basics

• Imaging Gradient Coils turn on only during image
  acquisition
• Gradient coils control the MR signal making it
  vary in different spatial locations
• In addition to specifying the RF waves, the pulse
  sequence also instructs which gradient coils will
  activate at what time and for how long, making
  the MR signal vary over different locations
• This difference in MR signal over spatial
  locations is key to constructing the image

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Hardware Radiofrequency Coils Gradient Coils
Diagram from Magnet Lab Florida State University
Radiofrequency Coils both transmit the pulse
sequence and receive the resulting MR signal. For
this reason, they are also called Transceiver
Coils.
Gradient Coils (X, Y, Z) cause the MRI signal
to vary across spatial locations, assisting with
image production.
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Gradient Coil Orientations

• X Coil Varies signal left to right Sagittal
  Plane
• Y Coil Varies signal top to bottom Coronal
  Plane
• Z Coil Varies signal head to toe, names
  interchangeable
• Transverse Plane OR
• Axial Plane OR
• Horizontal Plane

Diagram from Wellesley College
21

• Planes of Orientation
• In Neuroimaging
• Axial, Transverse or Horizontal
• Sagittal Coronal

Images from Chapman Lab WRIISC-DC
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Contrasts

• Contrasts the intensity difference in tissues
  measured by an imaging system
• Pulse sequences highlight these different
  contrasts
• Selected Types of Contrasts
• Static Contrasts sensitive to properties of
  atomic nuclei
• T1-weighted, T2-weighted, proton density
• Motion Contrasts sensitive to movement of atomic
  nuclei
• Diffusion Weighted Imaging, Perfusion Imaging

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Processing Quantitative MRI

• The pulse sequence gives us a basic picture
• To get good quantitative data, the images have to
  be cleaned up and normalized (via template)

Images from Chapman Lab WRIISC-DC
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Analyzing Quantitative MRI

• Once processed, structures within images can be
  analyzed (i.e., for size or intensity)
• The smallest square-shaped element in a 2-D
  picture is a pixel. In a 3-D image, it is
  called a voxel
• Voxels are usually grouped together into one or
  more regions-of-interest (ROI) for analysis

Image from Chapman Lab WRIISC-DC
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Volumetric Analysis

• A method to estimate the volume of specific
  brain structures or regions.
• Picture from Athinoula A. Martinos Center for
  Biomedical Imaging

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Volumetric Analysis

• The volume of specific brain structures or
  regions can be compared between patients or
  groups
• Gross structure can be assessed by analysis of
  structural MRI

Athinoula A. Martinos Center for Biomedical
Imaging
Images from Chapman Lab WRIISC-DC
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Volumetric Analysis

• Manual Methods

• Automated Methods

• Manually drawn
• High anatomic validity
• (gold standard)

• Extensive use of algorithms/atlas templates
• Reduction of anatomic validity

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Volumetric Analysis

• Manual Methods

• Automated Methods

• Time-intensive
• Inter-rater reliability concerns

• Allows high throughput efficient workflow
• Eliminates multiple rater effects

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Automated Volumetric Analysis

• Uses an algorithm to
• Strip away skull and facial tissue in the image
• Find border between the gray matter and
  subcortical white matter
• Find border between the gray matter and the pia.

Image from Chapman Lab WRIISC-DC
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Automated Volumetric Analysis

• Registers image to atlas template
• automatically parcels brain into regions based
  on
• Atlas template
• Anatomic properties of the subject brain.

Images from Chapman Lab WRIISC-DC
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Use of Volumetric Analysis

• Automated programs accept standard clinical MRI
  images and produce objective results independent
  of rater effects.
• The automatically parceled brain regions are each
  measured for total volume.

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Use of Volumetric Analysis

• These amounts can be averaged into groups and
  group differences can be computed.
• Volumetric differences are seen in many disease
  conditions such as TBI, Alzheimers, epilepsy,
  and depression

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Diffusion Tensor Imaging (DTI)

• DTI measures the movement of water molecules in
  axonal bundles, also called tracts, fiber tracts
  or fasciculi.
• DTI analysis yields quantitative metrics
• Allows white matter tracts to be visualized and
  characteristics estimated in vivo

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What is a Tensor?

• MRI divides the brain into thousands of voxels.
• At each voxel, DTI creates a ellipsoid as a
  measurement area.
• The activity within the ellipsoid
• can describe the direction
• and magnitude of water
• diffusion
• A Tensor is a mathematical method of
  characterizing activity within multi-dimensional
  geometric objects (like the ellipsoid).

Image from Biomedical Imaging and Intervention
Journal
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Brownian Motion
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• Anisotropic Diffusion

• Isotropic Diffusion

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DTI Metrics

• Most Commonly Metrics Used
• Fractional Anisotropy (FA) Directionality of
  diffusion
• Mean Diffusivity (MD) Diffusion averaged in all
  directions
• Axial Diffusivity (AD) Magnitude of diffusion
  parallel to the axonal tract (diffusing down the
  length of axons)
• Radial Diffusivity (RD) Magnitude of diffusion
  perpendicular to the axonal tract (diffusing
  across the width of the axon)

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Axial vs. Radial Diffusivity
Axial Diffusivity
Radial Diffusivity
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Strengths and Limitations of DTI
Strengths
Limitations

• Measures white matter in vivo
• Non-invasive, no ionizing radiation
• Can be combined with functional and behavioral
  measures
• Is relatively fast (8 minutes per scan)

• Regions with complex white matter configurations
  can confound the measurement
• Is less informative about grey matter
• Sensitivity to motion artifacts
• Measure is indirect, diffusion is only a
  correlate of fiber integrity

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Major Functional Imaging Methods
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Changes in Functional ActivityPositron Emission
Tomography (PET)

• Positron Emission Tomography (PET) was the first
  neuroimaging technique to allow functional
  localization.
• Radioactively labeled isotopes are transmitted
  into the bloodstream.
• Metabolism is observed.

Public Domain image courtesy of Jens Langer
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Changes in Functional ActivityMetabolism and
Brain Function

• Greater metabolism associated with higher
  activity in a given brain area.
• Differences in brain activity can result from a
  range of factors including
• transient neurocognitive conditions
• long-term changes in quantities of
  neurotransmitters receptors, or neurons
• permanent structural damage.

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Strengths and Limitations of PET
Strengths
Limitations

• Allows us to measure brain function in real time
• Different tracers can be specified for different
  needs
• Can be combined with structural imaging as well
  as cognitive and behavioral measures

• Uses ionizing radiation which must be limited
  over the lifetime
• Tracer selection is limited unless a cyclotron is
  owned
• Labeled isotope decays quickly, limiting time of
  scan
• Measure is indirect, metabolism is only a
  correlate of neural activity

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Changes in Functional Activityfunctional MRI
(fMRI)

• Good temporal resolution
• Non-invasiveness
• Lack of ionizing radiation
• fMRI has supplanted PET as the most used
  functional neuroimaging technique.

Public Domain image
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Changes in Functional ActivityBOLD fMRI

• Like PET, fMRI is measuring neural activation
  indirectly.
• Activation detected through a natural phenomenon
  Blood-oxygen-level dependent (BOLD) signal.
• BOLD signal measures deoxygenated hemoglobin,
  which increases in areas of high neural activity.

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Changes in Functional ActivityStatistical
Aspects of fMRI

• The colored areas do not strictly represent
  anatomy, but instead show significant differences
  in levels of BOLD activation across 2 (or more)
  groups.
• These statistical maps are overlaid onto
  structural MRI images to help visualize where
  activity changes are taking place in the brain.

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Strengths and Limitations of fMRI
Strengths
Limitations

• Allows us to measure brain function in real time
• Can be combined with structural imaging as well
  as cognitive and behavioral measures
• Superior temporal resolution (compared to PET)
  allows activity to be correlated with a series of
  1-2 second events, rather than over longer blocks
  of time
• Non-invasive, no ionizing radiation

• Measure is indirect, BOLD is only a correlate of
  neural activity
• Hemodynamic response for a 1 second activity can
  last for over 10 seconds, confounding results
• More susceptible than PET to motion artifacts

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Contact Us

• ADDRESS Veterans Affairs Medical Center
• 50 Irving Street NW, MS 127
• Washington, DC 20422
• PHONE [phone] Ext. 7553
• EMAIL Julie.Chapman_at_va.gov
  OR Chapman.Research_at_va.gov
• VISIT OUR WEBSITE
• http//www.warrelatedillness.va.gov/dc/