Functional MRI and BOLD EffectSeminar on Physical Fundamentals on Medical Imaging

Jonas Botz

17.06.2019

Table of content

• Introduction into functional MRI

• Methods for measuring brain activity

• Basics of Physiology and Physics

• BOLD Effect

• NMR Basics of BOLD-fMRI

• BOLD-fMRI in Practice

• BOLD-fMRI vs. PET

• Applications and Research 1

Introduction into functional MRI

• non invasive imaging technique to visualise ‘active’ brain areas

• test functions of brain areas

• study brain’s physiology

• most common realised by Blood Oxygenated Level Dependent fMRI (BOLD-fMRI)

[1]2

Methods for measuring brain activity

Action potential

Ion flux (Na+,K+,C2+)

Metabolism

Cerebral blood flow (CBF)

Cerebral blood volume (CBV)

OxyHb/DeOxyHb

EEG, MEG

MRI

PET, SPECT

PET, SPECT,MRI

PET,MRI

BOLD fMRI 3

Basics of Physics and Physiology

Local brain metabolism:

“There exists a coupling between neuronalactivity and local blood flow, so that

increased neuronal stimulation leads to alocal increase in blood flow.” *

• Constant delivery of oxygen and clearance of carbon dioxide by blood flow

• Oxygen is binded to haemoglobin in the lungs and released in the capillary

*ROY, C. W. and SHERINGTON, C. S. “ On the regulation of the blood-supply of the brain”. J. Physiol. (Lond.) 11: 85-108, 1890.4

Basics of Physics and Physiology

• Oxygenated Haemoglobin (OxyHb) is diamagnetic➡ no effect on the magnetic field

• Deoxygenated Haemoglobin (DeOxyHb) is paramagnetic➡ disturbs the magnetic field (natural contrast agent)➡ T2* constant decreases

*The Magnetic Properties and Structure of Hemoglobin, Oxyhemoglobin and Carbonmonoxyhemoglobin Proc Natl Acad Sci U S A. 1936 Apr; 22(4): 210–216; Linus Pauling and Charles D. Coryell

*

μso ∝ n(n + 2)

[2]

n = number of unpaired electrons

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BOLD Effect

(1) Stimulus

(2) Initial Dip

(3) ca. 5s to peak

(4) poststimulus undershoot1

2

3

4

small change of 0.5% to 15%

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𝑂𝑥𝑦𝐻𝑏𝐷𝑒𝑜𝑥𝑦𝐻𝑏

𝑂𝑥𝑦𝐻𝑏𝐷𝑒𝑜𝑥𝑦𝐻𝑏

𝑂𝑥𝑦𝐻𝑏𝐷𝑒𝑜𝑥𝑦𝐻𝑏

NMR Basics of BOLD fMRI

1. B0 alligns all spins

2. RF-Pulse flips the spins into xy-plane

3. Spins interact with each other Free Induction Decay (FID) Usually decays with time constant T2 Due to field inhomogenities the real time is T2* ca. ms

➡Use EPI for filling k-space

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BOLD signal for Gradient Echo sequence

S = S0 ⋅ e−TE⋅R*2 R*2 = R*2 (0) + R

=1

T*2

;

S0

R*2R

R*2 (0) > > R

TE

- Signal at TE=0 -> no dephasing

- Value for transverse relaxation

- Relaxation due to DeOxyHb

- Echo time

NMR Basics of BOLD fMRI

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NMR Basics of BOLD fMRI

Echo Planar Imaging (EPI):

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NMR Basics of BOLD fMRI

Echo Planar Imaging (EPI):

etc.

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NMR Basics of BOLD fMRI

Spatial resolution:

• Whole brain image requires about 200 x 180 x 180 mm3 volume coverage (cuboid)

• Typical spatial and temporal resolution of 3 x 3 x 3 mm3 and 3s

• Can be improved if not whole brain is covered (usually the case)with parallel imaging using multi-channel coils 1 x 1 x 2 mm3 ; 1.5 s

• Improved spatial resolution and decreased acquisition time reduces the SNR

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NMR Basics of BOLD fMRI

Noise:

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NMR Basics of BOLD fMRI

Noise:

fMRI data is very noisy ➡ have to repeat the experiment many times

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NMR Basics of BOLD fMRI

Noise:

fMRI data is very noisy ➡ have to repeat the experiment many times

physiological noise: • cardiac circuit ≈ 0.9 Hz • respiration ≈ 0.3 Hz • CSF movement • change in vessel diameter

} avoid tasks with the same frequency &

tell the patient not to take big breaths

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fMRI in Practice

What do you need for a fMRI experiment?

• as always: MRI scanner and patient

• goggles or mirror and screen

• response grips, joystick or similar

• headphones

• sync-box

• paradigm [2] [2]

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fMRI in Practice

What is a Paradigm?

• task the patient has to perform inside the scanner

• if possible one that ‘isolates a sense’

Examples:

• flickering checkerboard (vision); hand movement (motor)

• memory game (prefrontal cortex); ball game (lymbic system)

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rest

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fMRI in Practice

activation

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fMRI in Practice

activation

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fMRI in Practice

activation

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fMRI in Practice

activation

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fMRI in Practice

activation

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fMRI in Practice

activation

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fMRI in Practice

activation

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fMRI in Practice

activation

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fMRI in Practice

activation

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fMRI in Practice

activation

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fMRI in Practice

activation

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fMRI in Practice

activation

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fMRI in Practice

rest

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fMRI in Practice

Stimulation

rest rest rest restactivation activationactivation

(10-40)s (10-40)s (10-40)s (10-40)s(5-20)s (5-20)s (5-20)s

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fMRI in Practice

fMRI in Practice

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fMRI in Practice

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BOLD-fMRI vs. PETBOLD-fMRI PET

• Non invasive

• No contrast agents

• No radioactive isotopes

• Patient has to lie still

• Spatial resolution: ca. 2 mm3

• Noisy (acoustic)

• Cannot trace paths of chemicals (DTI)

• “Non invasive“

• Contrast agents

• Radioactive isotopes

• Small movement allowed

• Spatial resolution: ca. 5 mm3

• No noise

• Traces paths of chemicals

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Applications and Research

Applications:

• Localisation and test of cognitive functions

• Brain tumor surgery

• Care and treatment of epilepsy

• Diagnoses and management of Alzheimer‘s disease

• Diagnoses and management of psychiatric disease

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Applications and Research

Research:

• High field fMRI (7T)

• High resolution fMRI with EPIK

• Realtime fMRI and neurofeedback

• combination of fMRI with MEG or EEG

• combination of fMRI and PET

• Combination of fMRI, PET and MEG or EEG

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Summary

• BOLD-fMRI is used to visualise the active brain regions

• Deoxygenated haemoglobin is paramagnetic and thus disturbs the magnetic field

• non active brain regions have a shorter T2*

• the signal will decay faster

• with paradigms different brains’ parts can be activated and the response can be measured

• fMRI experiments are very noisy and have to be repeated several times

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Thank you for your attention!

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Bibliography• https://askabiologist.asu.edu/brain-regions [1]

• https://chem.libretexts.org/Bookshelves/Inorganic_Chemistry/Supplemental_Modules_(Inorganic_Chemistry)/Crystal_Field_Theory/Magnetic_Moments_of_Transition_Metals [2]

• https://www.nordicneurolab.com/en/research/hardware [3]

• https://www.mriquestions.com/index.html

• https://www.fz-juelich.de/inm/inm-4/DE/Forschung/MR-Physik /TeamFmriDE/fmri&PET&EEG/_node.html

• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3787513/

• lecture on fMRI Live Eikenes NTNU Trondheim 2018

• The physics of functional magneticresonance imaging (fMRI), Richard B BuxtonDepartment of Radiology, University of California, San Diego, 04.09.2013

• Physiological measurements using ultra-high field fMRI: a review, Sue Francis and Rosa Sanchez Panchuelo, University of Nottingham, 13.08.2014

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