Larissa Stanberry University of Washington Department of Statistics

1. Brief Introduction to Functional MRI Data Larissa Stanberry University of Washington Department of Statistics Red slides are due to Peter Jezzard, PhDFMRIB Centre, Oxford University, Hopefully, he does not mind

2. The 2003 Nobel Prize in Physiology or Medicine6 October 2003 The Nobel Assembly at Karolinska Institutethas today decided to award The Nobel Prize in Physiology or Medicine for 2003jointly to Paul C Lauterburand Peter Mansfield for their discoveries concerning "magnetic resonance imaging“ For their discoveries that have led to the development of modern MRI, which represents a breakthrough in medical diagnostics and research.

3. Nuclei of hydrogen atoms I • The human body weight has a high water content (about 2/3rd) • There are differences in water content among tissues and organs. • In many diseases the pathological process results in changes of the water content, and this is reflected in the MR image.

4. Nuclei of hydrogen atoms II • H2O molecule composed of H and O2 atoms. • The nuclei of the hydrogen atoms acts as microscopic magnet. • When the body is exposed to a strong magnetic field, the nuclei of the hydrogen atoms are directed • When submitted to pulses of radio waves, the energy content of the nuclei changes. After the pulse, a resonance wave is emitted when the nuclei return to their previous state. • The small differences in the oscillations of the nuclei are detected.

5. Nuclei of hydrogen atoms II • Using computer processing, it is possible to build up a 3-dim image that reflects the chemical structure of the tissue • differences in the water content • movements of the water molecules. • This results in a very detailed image of tissues and organs. • Pathological changes can be documented.

7. “… A brain MRI is a claustrophobic procedure in which you are passed through a tunnel so tight that it practically touches your nose and forehead and makes you feel that you might suffocate. I hated it..”Lance Armstrong My jorney back to life

8. A bit of NMR Physics I • Water is the most important site for MRI • concentration of protons in water • the dynamical properties of water. • The proton is a fundamental nuclear particle with charge, mass and spin • Spin can be thought of as a rotation of the nucleus about its axis • But the nucleus has a charge • Spinning charged object creates a magnetic field

9. A bit of NMR Physics II • spin J + mass of the proton, gives it an angular momentum m=gJ • Direction of m is random due to thermal random motion • When exposed to the strong magnetic field B0(1.5-3.0 T) the spins are lined up • The angle between the magnetic dipole moment m and B0 for the hydrogen protons is +/-53o44’’(H atoms point up or point down) • Magnetic moments precess around the applied field with Larmor frequency, m xy(t)= mxy(0)e-igBot m z(t)= mz(0)

10. A bit of NMR Physics III • To detect magnetization, a coil of wire is connected to a sensitive amplifier, which is in turn tuned to the Larmor frequency. • The rotating magnetic field will induce a tiny NMR signal in the coil, which oscillates at the Larmor frequency. • Only the time varying part of the magnetization is capable of inducing a signal in the coil • Only the transverse component in is detectable

11. A bit of NMR Physics IV • The transverse component of the magnetization is 0 • To generate an NMR signal, the magnetization must be tipped away away from the equilibrium alignment • To achieve this, the object is exposed to an alternating magnetic field B1 magnetic field tuned to the Larmor frequency. (a.k.a RF pulse , since the Larmor frequencies are typically in the Mhz range) • The flip angle ~ duration and strength of B1 field • The magnetization can be tipped to any angle

12. A bit of NMR Physics V • Each spin experiences a slightly different magnetic field • Each spin will have a slightly different precession frequency • When B1is removed, the system returns to its original state.. • M precess around B0 : free precession. • Longitudinal relaxation: the recovery of the longitudinal component (the projection on B0 ). • The transverse component is destructed: transverse relaxation.

13. A bit of NMR Physics VI In rotating frame the transverse and longitudinal component from the Bloch’s equation • Mz0is the longitudinal magnetization at thermal equilibrium. • This holds for “slowly” relaxing spins (liquid state molecules) • T1, T2are defined by the tissue, T1 >>T2. • The length of the precession period depends on T2 (ms) • Enables the detection of MR signal. • The magnitude of the signal depends on the # of spins, B0, T2 B1

16. A bit of NMR Physics VII • Multiple RF pulses generate echoes, two sided signals, where one side is due to the refocusing of the transverse magnetization and another side is due to the dephasing period. • Gradient field is a special kind of the magnetic field whose z-component varies linearly along a gradient direction. • The external magnetic field and RF pulse excite the spins at different spatial locations in the same way. .

17. Pulse Sequences • Demo

18. BOLD Contrast Mechanism I • Objects counteract in the presence of the external magnetic field. • These counteractions distort the applied field. • Diamagnetism a weak (less then ten parts per million) repulsion in a magnetic field generated by the current of the orbiting electron. All materials are naturally diamagnetic. • Paramagnetic materials have a dipole aligned with the magnetic field producing an additive internal field. Present in materials which have unpaired electrons. • Most proteins and tissue water are diamagnetic.

19. BOLD Contrast Mechanism II • BOLD (blood-oxygen-level-dependent) is based on physiological responses related to brain activation. • Deoxygenated Hb used as the source for the contrast. • HbO2 acts like a typical diamagnetic. • But Hb is paramagnetic. • Hb makes up nearly 15gm/100cm3 of the blood content • Deoxygenated red cells and blood vessels become a little magnets distorting the magnetic field around them.

20. BOLD Contrast Mechanism MR signal time Stimulus Stimulus Deoxygenated blood, because of its paramagnetic nature, leads to local magnetic field distortions between vasculature and surrounding brain parenchyma. This creates increased spin-spin dephasing of the MR signal in those regions, and as a result, there is reduced signal in these areas as compared to oxygenated hemoglobin.

21. BOLD Contrast Mechanism III • Activation  Rapid depletion of oxygen • The fraction of the paramagnetic Hb increases • Signal goes down below the baseline • Initial dip (~0.5-1.0s) very subtle, observed at the field strength > 2T. • The feeding arteriole dilates • Blood flow increases (due to the flow velocity rather than the volume) • Increase in O2 consumption < increase in CBF • The fraction of HbO2 increases in the capillary and veins • Since Hb decreases the MRI signal goes up • The signal increase ~2-3% of the baseline at 1.5Tesla. • Overshoot phase, due to the slow adjustment of the CBV to the changes in the stimulation state. (The stimulus is over, but the elevated blood volume persist even though the blood flow drops)

22. Typical fMRI Data

23. Typical fMRI Data II

24. Typical fMRI Data II

25. Motion Artifacts

26. Activation from left hand motor paradigm Left cerebellar activation Right motor cortex activation

27. Auditory activation Task: subject was given auditory instructions for the timing of the finger tapping (right, left, stop)

28. Important Noise Sources in fMRI • Signal drift with frequency ~ <0.015 Hz (T > 70 s) • Gradient instabilities • Low frequency oscillations < 0.1 Hz ( 60 s >T > 10 s) • Functional connectivity • Respiratory oscillations ~ 0.2 Hz (T ~ 5 s) • Cardiac oscillations ~ 1 Hz (T ~ 1 s) • Motion induced correlations

30. Left Jugular Vein

31. Right Internal Carotid Artery