Functional Magnetic Resonance Imaging (fMRI)

Beth Meyerand, PhDDepartment of Medical Physics

University of Wisconsin-Medical SchoolMadison, Wisconsin

Outline:

Introduction to fMRI physics (“BOLD”)

Overview of post-processing / analysis

Review of fMRI paradigms and procedures

Clinical applications

Blood Oxygen Level Dependent (BOLD) Imaging

* Requires a difference in oxygenation states

“ACTIVE” (increased oxyhemoglobin)

compared to

“RESTING” (decrease oxyhemoglobin)

• fMRI measures a blood flow (“hemodynamic”)effect, therefore it is only an INDIRECT measure of neuronal activity

How Are MR Images Affected By Oxygen Changes?

Hemoglobin: its magnetic properties depend on its oxygenation state.

•Oxygenated Hemoglobin-diamagnetic, like water and cellular tissue.

•Deoxygenated Hemoglobin- more paramagnetic than tissue, produces a stronger MR effect.

If an appropriate imaging sequence is selected, these differences in oxygen levels may be large enough to affect MR image intensity (T2*, or susceptibility).

Blood Oxygen Level Dependent (BOLD) Imaging

Cortical activation

Increase in cerebral metabolism

Increase CBF and CBV

Oxygen delivery exceeds oxygen demand

Oxygenation of venous pool increases

Concentration of dHb decreases

fMRI signal increase (< 5% at 1.5T)

BOLD signal time course

Signal(%) 3

0 20 40

delay

2

1

Time (seconds)

-1

Task, or stimulus timing

start stop

Echo Planar Imaging

•Imaging the whole braininvolves acquiring ~20 slicesthat are 6-7 mm thick spaced apart by 1 mm.

•The trade-off for fast scanning is low spatial resolution.

•To study brain function (changes in oxygen levels) we acquire over 100 whole brainimages collected over a time span of a few minutes.

fMRI Data Acquisition

x 100 repetitions = 100 time

points

time

signal

n slices

If 100 whole brain images are acquired in a scan, each voxel will be represented by a time series of 100

time points.

Overview of typical fMRI analysis procedures

- Motion correction

- Spatial smoothing

- Image co-registration

- Generation of statistical maps of BOLD response

- Selective interpretation of results

“pre-processing “ steps

fMRI “pre-processing”

uncorrected time courses

fMRI “pre-processing”

motion corrected time courses

fMRI “pre-processing”

motion corrected& spatially smoothed time courses

fMRI post-processingSpatial smoothing

- Increases SNR

- Some fMRI analysis software requires spatial smoothing as part of the analysis

Before After

fMRI post-processingMotion correction

- choose a time point in the middle of your time series

- register all images in time series to that time point

Before After

fMRI post-processingMotion correction

fMRI post-processingMotion correction

– effects on the time course

Before After

fMRI post-processing

EPI co-registration with high resolution anatomicals

- register (align in 3D space) EPI data to anatomicals

- sometimes very challenging due to susceptibility effects

- automatic or manual

fMRI post-processingImage registration

Left - Right

fMRI post-processingImage registration

Inferior - superior

fMRI post-processingImage registration

Roll

fMRI post-processingImage registration

Pitch

fMRI “pre-processing”EPI co- registration with high resolution anatomicals

How Do You Determine the “Active” Voxels?

Time

Sig

nal I

nten

sity

•After masking out the voxels outside the brain, we are left with ~15,000 voxel time series.

•The time series must be analyzed to determine the areas of activation during the task.

Task Performed:

task

rest

Which voxels best fit this model?

Time

Sign

al In

tens

ity

“Reference Function” of task performed:

Task Timing:

task

rest

Determining “Activation” Areas in fMRI

At every voxel, a test statistic is computed.

Functional Maps

A color intensity value is given corresponding to the value of this statistic.

Statistical Analysis

Paired t-test - used when 2 groups of data are correlated; thesame subject is scanned during activation (ON) and rest (OFF)periods.

NSXXt 21−=

Difference between the means of two groups divided by the standard error of the mean

Determining “Activation” Areas in fMRI

Functional maps after applying threshold

The statistically significant voxels are determined according to the sampling distribution.

Determining “Activation” Areas in fMRI

Functional maps after applying threshold

The statistically significant voxels are determined according to the sampling distribution.

…and then overlaid on co-registered anatomical images

Determining “Activation” Areas in fMRI

Functional maps at varying thresholds:

t > 4 t > 5t > 2

Software for fMRI data processing & display

• BrainWave GE Medical Systems

• Advanced Neuro Siemens Medical Systems

• IView Phillips Medical Systems

MRI vendor-

specific software

Unix-based

shareware• AFNI National Institutes of Health

• SPM Wellcome Dept. of Imaging Neuroscience

Other fMRI-

specific software

• Brain Voyager Brain Innovation B.V.

• Med-X Sensor Systems

fMRI acquisition set-up

LCD projector

Laptop

Stereo system

headphones

Projection screen

RF coil mirror

MRI magnet Scanner control room

fMRI paradigms for clinical patients

Pick and choose:

• Motor • Language

• Sensory• Cognitive

memoryvisual organizationcomputation

• Visual

• Auditory

fMRI paradigms:alternating-hand finger tapping task

Right hand task cycles

Left hand task cycles

restrestrestrestleftleftleftleft

rightright

rest

rightright

• 4 cycles each of right hand, left hand, and rest

• 20-second task epochs

fMRI paradigms:alternating-hand finger tapping task

LR

Yellow/orange = right hand Blue/cyan = left hand

Comparative hemispheric responses in primary sensorimotor, thalamus, putamen, superior and inferior cerebellum

fMRI somatotopic motor mapping A B

Presurgical fMRI mapping with multiple motor paradigms:A) alternating-hand finger tapping taskB) foot/ankle movement task

Comparison between finger motor task & palm tactile stimulation

Finger motor task Right hand Palm tactile stimulation Right hand

LL

Sensory Paradigms

Propofol-sedated 3 year old with right parietal mass- left hand palm stimulation

fMRI language paradigms

• Antonym generation

• Word generation from letters

• Alphabet letter generation

• Word generation from categories

• Synonyms task

• Text reading / comprehension

• Narrated text

Expressive

language

Receptive

language

covert language generation paradigms

Word generation from antonyms, letters, or categories

Simple block paradigms for robust signal localizationtask

rest

Task is performed silently to minimize head motion

Covert performance precludes patient monitoring, and motor vocalization response

Language generation paradigms

• Left-frontal gliomaL L

category word generation antonym word generation

• Repeated tasks increase confidence

fMRI of language networks Text reading paradigm

Text reading cycles

Letter stringscycles

restrestrestrestlettersletterslettersletters

texttext

rest

texttext

…

…

…

• 10 cycles each of descriptive text, letter strings, and blank screen fixation

• 8-second task epochs

fMRI of language networks

L

Text reading paradigm

Primary visual stimulus paradigm

8Hz checkerboard

fixation

Primary visual stimulusLeft occipital lesion

R

• fMRI response absent in affected hemisphere

Interpretation of clinical fMRI for presurgical

mapping

Guidelines and caveats

Interpretation of clinical fMRI for presurgical mapping

Caveats and limitations:• Inspect mapping for technical adequacy

• Extent of BOLD response is not directlyrelated to functional extent of cortex

• fMRI relies on a hemodynamic effect, doesnot directly measure neuronal activity

Interpretation of clinical fMRI for presurgical mapping

Caveats and limitations:

• Some tumors have been reported toaffect hemodynamic autoregulation

• Disturbances in cerebral blood flow andmetabolism can affect BOLD fMRI

• EPI susceptibility-related signal loss canmask regions of eloquent cortex

Effect of Pathology - AVM

• Patient with extensive rightfrontal-temporal AVM

• Text listening paradigm, no functional response seen inright superior temporal gyrus

L

> 480

360

240

120

• Temporal signal-to-noise map of the EPI signal shows low SNR in AVM region

• BOLD response could bemasked by hemodynamic instability

R

Effect of Pathology - Susceptibility

Activationabsent

R

Patient with reoccurring left frontal glioma, previous resection

• Word generation paradigm, no functional response seen inleft inferior / middle frontal gyri, right hemisphere languagedominance indicated

Effect of Pathology - Susceptibility

• EPI signal intensity mask shows region of susceptibility-induced signal loss

Effect of Pathology - Susceptibility

• EPI signal intensity mask shows region of susceptibility-induced signal loss

The furture is here!

AcknowledgementsThank you to the faculty, staff and

students at Univ. Wisconsin-Medical School

Chad H. Moritz fMRI Research Program ManagerVictor Haughton professor of NeuroradiologyHoward Rowley professor of NeuroradiologyBehnam Badie professor of NeurosurgeryRobert Dempsey professor of NeurosurgeryBruce Hermann professor of NeurologySterling Johnson professor of Neurology

Contact: memeyerand@wisc.edu