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Functional Magnetic Resonance Imaging Dr. Matthijs Vink Rudolf Magnus Institute of Neuroscience University Medical Centre Utrecht Functional MRI Group Utrecht. m.vink@azu.nl - 2006. Structure vs function. Functional MRI (fMRI) studies brain function . MRI studies brain anatomy .

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Slide1 l.jpg

Functional Magnetic Resonance ImagingDr. Matthijs VinkRudolf Magnus Institute of Neuroscience University Medical Centre Utrecht Functional MRI Group Utrecht

m.vink@azu.nl - 2006


Structure vs function l.jpg

Structure vs function

Functional MRI (fMRI) studies brain function.

MRI studies brain anatomy.


Slide3 l.jpg

Localization of functions

  • Specific brain areas have specific cytoarchitecture

  • Localization of function (old idea) vs network function (new idea)


Mri vs fmri l.jpg

MRI vs fMRI

Structural MRI  acquire image of whole brain in 8 minutes

Functional MRI  acquire image of whole brain every 0.5 seconds


Fmri scans example slices l.jpg

fMRI scans – example slices

  • scan technique

  • 3D PRESTO

  • resolution

  • 4*4*4 mm voxels

  • acquired scantime

  • 0.5 seconds


The idea behind fmri l.jpg

Functional MRI  acquire image of whole brain every 0.5 seconds

task

task

task

task

task

task

task

rest

rest

rest

rest

rest

rest

rest

The idea behind fMRI

Signal value over time in one voxel

Example task-related activity in a voxel:

Signal value


Fmri single subject data l.jpg

Moving fingers

Moving tongue

Watch flashing light

Think words

Short-term memory

fMRI: Single subject data

  • fMRI developed from the 1990’s

  • Allows for single subject data


Background of fmri l.jpg

Background of fMRI

  • First BOLD-fMRI study published in 1992 by Ogawa et al

    • uses deoxygenated haemoglobin as contrast agent

      Advantages of fMRI:

  • no injection of chemicals (such as PET)

  • high spatial resolution (1-4 mm)

  • fast (0.5 sec per scan,average 2 sec)

  • widely available (MRI scanner in every hospital)


Slide9 l.jpg

The MRI scanner...

Promotional photo, Philips


Slide10 l.jpg

The MRI scanner... is a very strong magnet!

Not a promotional photo


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Subject has to be metal-free

Inhomogeneous magnetic field

due to hairband

Homogeneous magnetic field

Scanner safety! Strict safety protocol


Background of fmri physics 1 2 l.jpg

Background of fMRI – physics 1/2

Why do you need a magnet?

No clear direction of protons


Background of fmri physics 1 213 l.jpg

Background of fMRI – physics 1/2

Why do you need a magnet?

B0

Apply magnetic field :

(i.e. place subject in scanner…)


Background of fmri physics 1 214 l.jpg

Background of fMRI – physics 1/2

Why do you need a magnet?

B0


Background of fmri physics 1 215 l.jpg

Background of fMRI – physics 1/2

Why do you need a magnet?

B0


Background of fmri physics 1 216 l.jpg

Background of fMRI – physics 1/2

Why do you need a magnet?

B0


Background of fmri physics 1 217 l.jpg

Background of fMRI – physics 1/2

Why do you need a magnet?

B0

align with magnet (B0) (or against)

# depends upon strength of B0


Background of fmri physics 2 2 l.jpg

excitation

relaxation

precession motion in a magnetic field

 radio wave is transmitted (echo)

 Frequency

 Phase

Background of fMRI – physics 2/2

stability

aligned with magnetic

field (low energy state)


Basis of the fmri signal physiology l.jpg

task

task

task

task

rest

rest

rest

rest

Basis of the fMRI signal - physiology

  • Place subject in scanner (protons align with magnet)

  • Start scanning while subject performs a task :

  • Rest periods  no activity (baseline)

  • During task  neuronal firing increases

  • Metabolism increases

    • consumption of glucose increases

    • consumption of oxygen increases

  • Bloodflow increases to supply oxygen (local magnetic field becomes very homogeneous)

  • Surplus of oxygen  BOLD fMRI signal increases (by 1-5 %)


Bold effect l.jpg

t=0 s

100

Baseline:

onset of stimulus

t=1 s

99

Oxygen

consumption

Small field distortion

t=6 s

102

Oxygen supply

maximum fMRI signal

Local field becomes homogeneous

BOLD effect

Blood

Oxygenation

Level

Dependent

effect


Bold effect where physics and physiology meet 1 2 l.jpg

BOLD effect – where physics and physiology meet 1/2

oxyhaemaglobin low

deoxyhaemglobin high

oxyhaemaglobin high

in-homogeneous field (out phase)

homogeneous field (in phase)

3-4 mm


Bold effect where physics and physiology meet 2 2 l.jpg

102

BOLD effect – where physics and physiology meet 2/2

Mxy

Signal (T2* relaxation) during task

Dephasing (spin-spin interactions)

Signal during rest

100

BOLD-contrast

(activation)

RF pulse

time

TE time (echo read-out)

(B0)


The fmri experiment l.jpg

The fMRI experiment


Fmri setup l.jpg

fMRI setup

  • Philips Gyroscan 1.5 Tesla

    • 1 Tesla = 10,000 Gauss

    • Earth’s magnetic field = 0.5 Gauss

    • 1.5 Tesla = 1.5 x 10,000  0.5 = 30,000 X Earth’s magnetic field

Projection screen

for computer tasks

MRI-compatible button box

mirror


Fmri data analysis l.jpg

task

task

task

task

task

task

task

rest

rest

rest

rest

rest

rest

rest

fMRI data analysis

  • Which brain regions are involved in performing the task?

  • Changes in the signal that correlate with the task (input function)

  • This is done in every voxel separately


Fmri preprocessing l.jpg

fMRI preprocessing

  • Before the data (series of fMRI images) is ready for statistical analysis:

  • Correct for movement of the head during the experiment

    • To look at signal changes over time in the same voxel (brain region)

  • Transform the brain to a standard brain (enable group comparisons)


Motion correction 1 5 l.jpg

Motion correction 1/5

1. Position of the head over time

scan 1 scan 2 … scan 99 … scan 820

time


Motion correction 2 5 l.jpg

Motion correction 2/5

2. Determine position of head during first scan

scan 1 scan 2 … scan 99 … scan 820

time


Motion correction 3 5 l.jpg

Motion correction 3/5

3. Use first scan as reference position

scan 1 scan 2 … scan 99 … scan 820

time


Motion correction 4 5 l.jpg

Motion correction 4/5

4. Determine motion correction parameters

+

scan 1 scan 2 … scan 99 … scan 820

time


Motion correction 5 5 l.jpg

Motion correction 5/5

5. Apply the parameters : resample the scans

scan 1 scan 2 … scan 99 … scan 820

time

Difficult to correct for effect of movement (in a magnetic field) on SNR throughout brain!


Transforming to standard brain l.jpg

?

?

?

?

?

=

=

=

=

=

Individual brains after normalization

Transforming to standard brain

Individual brains

MNI

template

Can the brains of people be standardized at all?


Basic fmri image analysis l.jpg

task

task

task

task

task

task

task

rest

rest

rest

rest

rest

rest

rest

Basic fMRI image analysis

The fMRI time-series data (eg 920 brain scans in 20 minutes):

Look for task related activity in every voxel (activity that covaries with the task):

Signal value over time in one voxel

Example task-related activity in a voxel:

Signal value


Multiple regression l.jpg

Model (X)

Effects of interest

(TASK)

Effects of no-interest

Multiple regression

Signal in

one voxel

=

+ error

Data (Y)

(after realignment)

Voxel-based statistics


Example motor stimulation l.jpg

task

ViewMagic © Matthijs Vink

Example : motor stimulation

Regression-coefficient  height of signal increase compared to baseline

T-value  significance of that increase compared to noise


Slide37 l.jpg

fMRI tasks

  • Essential to develop an fMRI compatible task:

  • Avoid movements, talking, listening (motion artefacts, noise)

  • Keep it simple (interpretation of results)

  • Need for control task (helps interpretation)

  • Measure task performance (helps interpretation)


Schizofrenie l.jpg

Schizophrenia

Schizofrenie

  • symptoms:

    • positive (delusions, auditory hallucinations)

    • negative (social withdrawal, loss of initiative)

    • cognitive (memory, attention, information processing)


Language tasks l.jpg

Language tasks

Task (30 secs)

Rest (30 secs)

Task (30 secs)

A

G

*

S

K

*

W

F

*

Block design

Verb generation (silent)

What happens during rest?

What happens during task?


Example fmri and language l.jpg

Example : fMRI and language

Healthy subjects : Language predominantly left


Slide41 l.jpg

Language and schizophrenia

Healthy

subjects

Schizophrenia

patients

Iris Sommer, work in progress


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Interpretation

Additional activation in right side in schizophrenia

So what?

How to figure out what that means?

fMRI gives info on BOLD activation, but not function

Apply repetitive TMS to right-sided language area to

suppress auditory hallucinations

Iris Sommer, work in progress


Hoe werkt dat bij schizofrenie l.jpg

hallucinations

delusions

loss of initiative

information

overload

Example : fMRI as a tool for genetic research

Hoe werkt dat bij schizofrenie?

Schizophrenia:


Hoe werkt dat bij schizofrenie44 l.jpg

Example : fMRI as a tool for genetic research

Hoe werkt dat bij schizofrenie?

Schizophrenia:

hallucinations

delusions

loss of initiative

information

overload


Hoe werkt dat bij schizofrenie45 l.jpg

Example : fMRI as a tool for genetic research

Hoe werkt dat bij schizofrenie?

Schizophrenia:

hallucinations

delusions

loss of initiative

information

overload


Hoe werkt dat bij schizofrenie46 l.jpg

Example : fMRI as a tool for genetic research

Hoe werkt dat bij schizofrenie?

Schizophrenia:

hallucinations

delusions

loss of initiative

information

overload


Hoe werkt dat bij schizofrenie47 l.jpg

Example : fMRI as a tool for genetic research

Hoe werkt dat bij schizofrenie?

Schizophrenia:

hallucinations

delusions

loss of initiative

information

overload


Hoe werkt dat bij schizofrenie48 l.jpg

Example : fMRI as a tool for genetic research

Hoe werkt dat bij schizofrenie?

Schizophrenia:

hallucinations

delusions

auditory

loss of initiative

information

overload

visual


Hoe werkt dat bij schizofrenie49 l.jpg

Example : fMRI as a tool for genetic research

Hoe werkt dat bij schizofrenie?

Schizophrenia:

hallucinations

delusions

auditory

loss of initiative

information

overload

visual


Hoe werkt dat bij schizofrenie50 l.jpg

Example : fMRI as a tool for genetic research

Hoe werkt dat bij schizofrenie?

Schizophrenia:

hallucinations

delusions

auditory

loss of initiative

information

overload

visual


Hoe werkt dat bij schizofrenie51 l.jpg

Example : fMRI as a tool for genetic research

Hoe werkt dat bij schizofrenie?

Schizophrenia:

hallucinations

delusions

auditory

loss of initiative

information

overload

visual


Hoe werkt dat bij schizofrenie52 l.jpg

Example : fMRI as a tool for genetic research

Hoe werkt dat bij schizofrenie?

Schizophrenia:

hallucinations

delusions

auditory

positive

loss of initiative

information

overload

negative

visual


Hoe werkt dat bij schizofrenie53 l.jpg

Example : fMRI as a tool for genetic research

Hoe werkt dat bij schizofrenie?

Schizophrenia:

hallucinations

delusions

auditory

positive

loss of initiative

information

overload

negative

visual


Hoe werkt dat bij schizofrenie54 l.jpg

Example : fMRI as a tool for genetic research

Hoe werkt dat bij schizofrenie?

Schizophrenia:

hallucinations

delusions

auditory

positive

loss of initiative

information

overload

negative

visual


Hoe werkt dat bij schizofrenie55 l.jpg

Example : fMRI as a tool for genetic research

Hoe werkt dat bij schizofrenie?

Schizophrenia:

hallucinations

delusions

auditory

positive

familiar

loss of initiative

strangers

information

overload

negative

visual


Hoe werkt dat bij schizofrenie56 l.jpg

Example : fMRI as a tool for genetic research

Hoe werkt dat bij schizofrenie?

Schizophrenia:

hallucinations

delusions

auditory

positive

familiar

loss of initiative

strangers

information

overload

negative

visual

Etc…


Hoe werkt dat bij schizofrenie57 l.jpg

Example : fMRI as a tool for genetic research

Hoe werkt dat bij schizofrenie?

Schizophrenia:

Label for multiple combinations of multiple symptoms

How to find schizophrenia genes?


Fmri als endophenotype l.jpg

Gene

sequencing

Intra-cellular mechanisms

molecular biology

Inter-neuronal communication

electrophysiology / neuropharmacology

Neuronal network / circuit

neurophysiology / lesion

Brain function

brain imaging

Behavioural measure

psychological tests

Symptom

clinical measures

diagnosis

Psychiatric disorder

Example : fMRI as a tool for genetic research

fMRI als endophenotype


Slide59 l.jpg

Example : fMRI as a tool for genetic research

BASELINE motor task

100% GO

GO ONLY

+ + +

+ + X

Press right

+ + +

X + +

Press left

+ + +

Vink et al, Hum Brain Map, 2005


Slide60 l.jpg

Baseline task


Slide61 l.jpg

CONTROLLED motor task

80% GO

20% STOP

X + +

+ + X

GO/STOP

+ + +

+ + +

Press right

Delay

X + +

STOP!

Press left

Example : fMRI as a tool for genetic research

BASELINE motor task

100% GO

GO ONLY

+ + +

+ + X

Press right

+ + +

X + +

Press left

+ + +

Vink et al, Hum Brain Map, 2005


Slide62 l.jpg

CONTROLLED motor task


Hoe presteren de groepen l.jpg

A

Healthy controls (21)

Schizophrenia patients (21)

B

Healthy controls (15)

Siblings (15)

Example : fMRI as a tool for genetic research

Hoe presteren de groepen?

600

580

560

540

mean reaction time in ms (SEM)

520

500

480

460

GO

0%

20%

25%

33%

50%

GO

0%

20%

25%

33%

50%

ONLY

ONLY

Stop signal chance (%)

Vink et al, Biological Psychiatry, 2006


Wat gebeurt er in de hersenen l.jpg

A

Healthy controls (21)

Schizophrenia patients (21)

B

Healthy controls (15)

Siblings (15)

Example : fMRI as a tool for genetic research

Wat gebeurt er in de hersenen?

2

1.5

1

mean activation level (AU ±SEM)

0.5

0

0%

20%

25%

33%

50%

0%

20%

25%

33%

50%

GO ONLY

GO ONLY

Stop signal chance (%)

Stop signal chance (%)

Vink et al, Biological Psychiatry, 2006


Slide65 l.jpg

Example : fMRI as a tool for pre-operative function localization

Epilepsy

Remove part of the brain to stop epileptic attacks

Danger of distroying important brain regions / functions

How to decide where to cut?


Slide66 l.jpg

Example : fMRI as a tool for pre-operative function localization

Essential to get correct rendering of MRI image of brain

Rutten et al, Neuroimage, 2003


Slide67 l.jpg

Example : fMRI as a tool for pre-operative function localization

fMRI (yellow) vs ioESM (red)

Specificity vs sensitivity

fMRI  also non-essential activation

Rutten et al, Neuroimage, 2003


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