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Julie C. Chapman, PsyDDirector of Neuroscience

War Related Illness & Injury Study Center

Veterans Affairs Medical Center

Washington, DC

Assistant Professor of Neurology

Georgetown University School of Medicine

Clinical and Advanced Neuroimaging:A Primer for Providers

Patrick Sullivan, MANeuroimaging Lead, Chapman

LaboratoryWar Related Illness and Injury

Study Center Veterans Affairs Medical Center

Washington, DC

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Disclaimer

The views expressed in this presentation are those of the author and DO NOT reflect the official

policy of the

Department of Veterans Affairsor

the United States Government

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What is Neuroimaging?Since we cannot generally take

photographs of the brain in vivo, imaging technologies allow us to view the brain indirectly.

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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

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

Conventional

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Neuroimaging Methods:Conventional vs.

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)

Advanced

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Structural vs. Functional Neuroimaging 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)

Structural Methods

Functional Methods

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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 LabFlorida 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 LabFlorida 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 MRIsignal 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

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Planes of OrientationIn 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 ImagingImages from Chapman Lab WRIISC-DC

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Volumetric Analysis

Manually drawn High anatomic

validity (gold standard)

Extensive use of algorithms/atlas templates

Reduction of anatomic validity

Manual Methods Automated Methods

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Volumetric Analysis

Time-intensive Inter-rater

reliability concerns

Allows high throughput & efficient workflow

Eliminates multiple rater effects

Manual Methods Automated Methods

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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 LabWRIISC-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, Alzheimer’s, 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 directionand 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

Radial DiffusivityAxial Diffusivity

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Strengths and Limitations of DTI 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

Strengths Limitations

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Major Functional Imaging Methods

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Changes in Functional Activity:Positron 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 Activity:Metabolism 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 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

Strengths Limitations

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Changes in Functional Activity:functional 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 Activity:BOLD 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 Activity:Statistical 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 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

Strengths Limitations

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Contact UsADDRESS: Veterans Affairs Medical Center

50 Irving Street NW, MS 127 Washington, DC 20422

PHONE: (202) 745-8000 Ext. 7553

EMAIL: Julie.Chapman@va.gov ORChapman.Research@va.gov

VISIT OUR WEBSITE: http://www.warrelatedillness.va.gov/dc/