Functional Magnetic Resonance Imaging (fMRI) Beth Meyerand, PhD Department of Medical Physics University of Wisconsin-Medical School Madison, 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 Hemoglobindiamagnetic, 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

delay

2 1

-1

0

20

start

stop

Task, or stimulus timing

40

Time (seconds)

Echo Planar Imaging •Imaging the whole brain involves acquiring ~20 slices that 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 brain images collected over a time span of a few minutes.

fMRI Data Acquisition signal time

n slices

x 100 repetitions =

100 time points

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

“pre-processing “ steps

- Image co-registration - Generation of statistical maps of BOLD response - Selective interpretation of results

fMRI “pre-processing”

uncorrected time courses

fMRI “pre-processing”

motion corrected time courses

fMRI “pre-processing”

motion corrected & spatially smoothed time courses

fMRI post-processing Spatial smoothing - Increases SNR - Some fMRI analysis software requires spatial smoothing as part of the analysis Before

After

fMRI post-processing Motion 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-processing Motion correction

fMRI post-processing Motion 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-processing Image registration Left - Right

fMRI post-processing Image registration

Inferior - superior

fMRI post-processing Image registration

Roll

fMRI post-processing Image registration

Pitch

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

How Do You Determine the “Active” Voxels?

Signal Intensity

•The time series must be analyzed to determine the areas of activation during the task. •After masking out the voxels outside the brain, we are left with ~15,000 voxel time series. Task Performed: task

Time

rest

Which voxels best fit this model?

Signal Intensity

“Reference Function” of task performed:

Task Timing: task

rest

Time

Determining “Activation” Areas in fMRI At every voxel, a test statistic is computed. A color intensity value is given corresponding to the value of this statistic.

Functional Maps

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

X 1 − X2 t= S N

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

Determining “Activation” Areas in fMRI The statistically significant voxels are determined according to the sampling distribution.

Functional maps after applying threshold

Determining “Activation” Areas in fMRI The statistically significant voxels are determined according to the sampling distribution.

Functional maps after applying threshold …and then overlaid on coregistered anatomical images

Determining “Activation” Areas in fMRI Functional maps at varying thresholds:

t>2

t>4

t>5

Software for fMRI data processing & display • BrainWave GE Medical Systems MRI vendorspecific software

• Advanced Neuro Siemens Medical Systems • IView Phillips Medical Systems

Unix-based shareware

Other fMRIspecific software

• AFNI National Institutes of Health • SPM Wellcome Dept. of Imaging Neuroscience • Brain Voyager Brain Innovation B.V. • Med-X Sensor Systems

fMRI acquisition set-up LCD projector

Projection screen

RF coil

mirror

Laptop headphones Stereo system

Scanner control room

MRI magnet

fMRI paradigms for clinical patients Pick and choose: • Motor

• Language

• Sensory • Visual • Auditory

• Cognitive memory visual organization computation

fMRI paradigms: alternating-hand finger tapping task Right hand task cycles

Left hand task cycles

right rest

right

left rest

right

left rest

right

left rest

• 4 cycles each of right hand, left hand, and rest • 20-second task epochs

left rest

fMRI paradigms: alternating-hand finger tapping task

L

R

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 task B) foot/ankle movement task

Comparison between finger motor task & palm tactile stimulation Finger motor task Right hand L

Palm tactile stimulation Right hand L

Sensory Paradigms

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

fMRI language paradigms • Antonym generation Expressive language

• Word generation from letters • Alphabet letter generation • Word generation from categories • Synonyms task

Receptive language

• Text reading / comprehension • Narrated text

covert language generation paradigms Word generation from antonyms, letters, or categories Simple block paradigms for robust signal localization task rest

Task is performed silently to minimize head motion Covert performance precludes patient monitoring, and motor vocalization response

Language generation paradigms • Left-frontal glioma L

antonym word generation

L

category word generation

• Repeated tasks increase confidence

fMRI of language networks Text reading paradigm Text reading cycles

…

Letter strings cycles

… text

text letters rest

text letters

rest

text letters

rest

…

letters rest

rest

• 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 stimulus Left 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 directly related to functional extent of cortex • fMRI relies on a hemodynamic effect, does not directly measure neuronal activity

Interpretation of clinical fMRI for presurgical mapping Caveats and limitations: • Some tumors have been reported to affect hemodynamic autoregulation • Disturbances in cerebral blood flow and metabolism can affect BOLD fMRI • EPI susceptibility-related signal loss can mask regions of eloquent cortex

Effect of Pathology - AVM L

• Patient with extensive right frontal-temporal AVM • Text listening paradigm, no functional response seen in right superior temporal gyrus

R > 480 360 240 120

• Temporal signal-to-noise map of the EPI signal shows low SNR in AVM region • BOLD response could be masked by hemodynamic instability

Effect of Pathology - Susceptibility R

Activation absent

Patient with reoccurring left frontal glioma, previous resection • Word generation paradigm, no functional response seen in left inferior / middle frontal gyri, right hemisphere language dominance indicated

Effect of Pathology - Susceptibility

• EPI signal intensity mask shows region of susceptibilityinduced signal loss

Effect of Pathology - Susceptibility

• EPI signal intensity mask shows region of susceptibilityinduced signal loss

The furture is here!

Acknowledgements Thank you to the faculty, staff and students at Univ. Wisconsin-Medical School Chad H. Moritz Victor Haughton Howard Rowley Behnam Badie Robert Dempsey Bruce Hermann Sterling Johnson

fMRI Research Program Manager professor of Neuroradiology professor of Neuroradiology professor of Neurosurgery professor of Neurosurgery professor of Neurology professor of Neurology

Contact: [email protected]