1. Basis of the BOLD signal Ciara O’Mahony and Miriam Klein

2. Section 1: Basics of MRI Physics Section 2: What does BOLD reflect?

3. MRI scanner

4. A proton has a positive electric charge, and because it spins around itself, it produces a small magnetic field Miniature bar magnet with a north and south pole Spins (Spinning protons) Technique at the root of MRI and fMRI: Nuclear Magnetic Resonance  has to do with the magnetic properties of the nucleus of atoms Nucleus of the hydrogen atom: a single proton

5. Spins align with magnetic field B 0 Outside scannerInside scanner Strength of B 0 : 30.000 (1.5T) or 60.000 (3T) times the earth’s magnetic field (0.0005T) z M0M0

6. Spins precess like spinning tops: Larmor frequency Frequency of precession is directly proportional to the strength of the magnetic field. ω = γ · B 0 ω - frequency of precession = Larmor frequency y - gyromagnetic ratio (constant unique to every atom, i.e. hydrogen) B 0 - strength of magnetic field M 0`

7. Spins are perturbed by radiofrequency pulse We apply an electromagnetic pulse of the correct frequency (= radio frequency (RF) pulse with Larmor frequency) 90 degree pulse M0M0 M xy zz y y This (a) Perturbs the distribution of the spin up and spin down states (b) Aligns the phase of the spins

8. The longer and stronger the RF pulse, the more energy is absorbed, and the more the overall (red) magnetization vector M 0 flips ‘away’ from the z axes, i.e. the larger the flip angle α We can adjust the RF pulse such that it is exactly 90° as shown here More about RF pulse... α What means in phase? zz y y

9. What we can measure: T1, T2, and T2* When RF pulse is turned off, spins want to go back to their original state, i.e. from to What will happen? (a)Spins go back to their preferred up/down states  T1 relaxation, slow (b)Spins dephase  T2 and T2* relaxation, quick M xy M0M0 zz y y

10. T1: Spins go back to up/down states T1 relaxation called longitudinal relaxation: along z-axis Absorbed energy partly given to tissue in the form of heat and partly retransmitted to RF receivers Time course of returning to equilibrium is described by exponential function  signal gets stronger in z-direction M0M0 zz y y

11. T1 image T1 is unique to every tissue: Time constant T1 is defined as the point where 63% of the magnetization M has recovered alignment with B 0 Slow recovery in CSF and quick in white matter

12. T2: Spins dephase Signal decay in xy plane described by exponential curve T2 relaxation called transverse relaxation: in xy plane Caused by spin-spin interactions The loss of signal in the xy plane produces our signal M xy zz y y

13. T2 image T2 is also unique to every tissue. Time constant T2 is defined as the point where 63% of the magnetization in xy has decayed.

14. Singer et al., 2006 The decay is faster than T2 would predict because of inhomogeneities in the magnetic field  what we measure is T2*  T2* is the apparent transverse relaxation What is T2*? time M xy M o sin  T2T2 T2*T2*

15. How has all this to do with brain activity? If other magnetic particles are present, T2* decay is even quicker When a brain area is active, less magnetic particles are present because more oxygen (oxyhemoglobin) is present (relative to deoxyhemoglobin) and so T2* relaxation is relatively slow So all we measure with fMRI/BOLD from a physics point of view are stronger or weaker inhomogeneities in the field due to more or less oxygen being present time M xy Signal M o sin  T 2 * task T 2 * control TE optimum S task S control SS Take-home message part 1: BOLD is a T2*-weighted contrast We are measuring a signal from hydrogen but the signal we get from hydrogen atoms is weaker when less oxygen (oxyhemoglobin) is present

16. Section 1: Basics of MRI Physics Section 2: What does BOLD reflect?

17. A Typical Neuron

18. Mostly to restore balance recycling of transmitter restore ion gradients Where does the brain use energy? Atwell & Iadecola, 2002 ATP: adenosine triphosphate: mainly produced through oxidative glucose metabolism

19. How is the energy supplied? Zlokovic & Apuzzo, 1998 Capillary networks supply glucose and oxygen

20. Haemoglobin Oxyhaemoglobin: diamagnetic Deoxyhaemoglobin: paramagnetic

21. What does BOLD measure? Changes in magnetic properties of haemoglobin: more oxyhaemoglobin increased signal more deoxyhaemoglobin decreased signal SO…we are NOT measuring oxygen usage directly

22. Task: relatively more oxyhaemoglobin; less field inhomogeneity; slower T2* contrast decay; stronger signal time M xy Signal M o sin  T 2 * task T 2 * control TE optimum S task S control SS Control: relatively more deoxyhaemoglobin; more field inhomogeneity; faster T2* contrast decay; weaker signal

23. Haemodynamic Response Depends On: cerebral blood flow cerebral metabolic rate of oxygen cerebral blood volume

24. Haemodynamic Response Function 1.‘initial dip’ 2.oversupply of oxygenated blood 3.decrease before return to baseline

25. Supply of blood is correlated with glucose and oxygen consumption Response is much slower than changes in neuronal activity Not affected by sustained hypoxia or hypoglycemia How is cerebral blood flow controlled?

26. by-products of neuronal spiking e.g. NO calcium signalling in astrocytes

27. What component of neural activity? Local Field Potential or Spiking? LFP: synchronized dendritic currents, averaged over large volume of tissue Could LFP increase without concomitant increase in mean firing rate? fMRI signal might reflect not only the firing rates of the local neuronal population, but also subthreshold activity

28. Overview: What are we measuring with BOLD?  the inhomogeneities introduced into the magnetic field of the scanner…  changing ratio of oxygenated:deoxygenated blood...  via their effect on the rates of dephasing of hydrogen nuclei

29. RealignmentSmoothing Normalisation General linear model Statistical parametric map (SPM) Image time-series Parameter estimates Design matrix Template Kernel Gaussian field theory p <0.05 Statisticalinference Where are we?

30. Thanks to... Antoinette Nicolle Nikolaus Weiskopf

31. References: http://www.simplyphysics.com/MRI_shockwave.html http://www.cardiff.ac.uk/biosi/researchsites/emric/basics.html Previous year’s talks Physic’s Wiki: http://cast.fil.ion.ucl.ac.uk/pmwiki/pmwiki.php/Main/HomePagehttp://cast.fil.ion.ucl.ac.uk/pmwiki/pmwiki.php/Main/HomePage Heeger, D.J. & Ress, D. (2002) What does fMRI tell us about neuronal activity?Nature 3:142. Atwell, D. & Iadecola, C. (2002) The neural basis of functional brain imaging signals. Trends in Neurosciences 25(12):621.