What are we measuring in fMRI?

Caroline Catmur

Jack Kelly

In BOLD fMRI, we are measuring: the inhomogeneities introduced into the

magnetic field of the scanner… as a result of the changing ratio of

oxygenated:deoxygenated blood… via their effect on the rates of dephasing of

hydrogen nuclei.

Ehhh???

Physics: underlying principles

• Hydrogen nuclei (1H): positively charged particles which spin around their axes, producing a (small) magnetic field.

• MDM: magnetic dipole moment: vector of themagnetic field of the nucleus.

When placed in a uniform magnetic field, (conventionally indicated by the z axis), the particles’ MDMs align with or against the field. A small percentage more align with the field than against, proportional to the strength of the field, giving the particles a net magnetization.

• The MDMs also precess around the axis of the field, at a resonant frequency dependent on the strength of field and type of nucleus, eg 64MHz for 1H in a 1.5T field.

So what goes on in the scanner?

• Place the nuclei (ie the brain) in a uniform magnetic field (the scanner).

• The next step: apply an RF pulse, frequency equal to frequency of precession of the nuclei, normally at 90° to the magnetic field. This ‘tips’ the MDMs of those nuclei which have this frequency of precession, ie we only ‘tip’ the 1H nuclei.

• So, the MDMs of the 1H nuclei are now

at 90° to the main field, ie in the x/y plane.

• Terminate the RF pulse and the nuclei relax: their MDMs return to the original orientation in the z dimension, and the energy released during relaxation is what is measured by the receiver coil.

• Three different relaxation times of interest in MRI: T1, T2 and T2*.

Phase

• Before the RF pulse, all the MDMs precess at the same frequency but not in phase.

• After they’re tipped, all precess in phase. Can think of it as all MDMs movingtogether: this produces a strong signal in the x/y plane.

• Once the RF pulse ends, begin to dephase: start to cancel each other out and the signal decays.

• Two reasons for this dephasing: inhomogeneities in the magnetic field, and ‘spin-spin’ interactions between neighbouring nuclei.

• Possible to correct for dephasing due to inhomogeneities in the field by applying another RF pulse at 180° to the initial pulse. Known as a spin-echo sequence.

Back to those relaxation times

• T1 relaxation: time course for the MDMs to return to their original (z) orientation.

T2 relaxation: time course of the breakdown of the magnetization in the x/y plane due to spin-spin interactions.

• T2* relaxation: time course of the breakdown of the magnetization in the x/y plane due to variations in the magnetic field. The T2* processes can be refocused using a 180° spin-echo sequence, though the T2 processes will still remain.

• Different tissues have different T1 and T2 relaxation rates.

• T1-weighted scan: measure signal at time when relative difference (between tissue types) in amplitudes of MDMs in z dimension is maximum.

• T2-weighted scan: measure at time when relative difference in amplitudes of MDMs in x/y plane is maximum.

• To get these different scans, change time between RF-pulse and measurement (TE), and between successive RF pulses (TR).

But why do we need to know all this?

• BOLD (blood oxygenation level dependent) contrast: measures inhomogeneities in the magnetic field due to changes in the level of oxygen in the blood. So it’s a T2* contrast.

• Oxygenated blood contains oxyhaemoglobin: red blood cells with O2 molecule attached. Not magnetic.

• Deoxygenated blood: deoxyhaemoglobin: red blood cells without O2. Magnetic.

• So if ratio deoxygenated:oxygenated blood is high, increases inhomogeneities in the magnetic field faster breakdown of magnetism in x/y plane (T2* relaxation) decrease in fMRI signal.

• If ratio oxygenated:deoxygenated is high, slower T2* relaxation less decrease in signal.

• So we can use the change in fMRI signal to infer the relative oxygenation of the blood.

So how do we get the actual information?

• Spatial localisation: ‘gradients’. Small magnetic field gradients (eg 30 mT/m) superimposed onto the main static magnetic field.

• Remember that the resonant frequency for a nucleus in a magnetic field depends on the field strength.

• So, differences in the resonance frequencies encode the positions of the nuclei along the gradient field.

• Switching the small gradients on and off is noisy!• Receiving the information: the RF coil both transmits and

receives. A volume coil images any part of the brain; a surface coil gives better images, but only for the nearest part of the brain, due to distortions. A phased array coil is a series of surface coils.

fMRI – neurophysiology

fMRI

Outline:

• What is BOLD?

• Correlation of BOLD with electrophys.

• How neurons cause CBF increases

• Localising BOLD

• Summation of BOLD

• Implications for cognitive studies

BOLD and MRI

• BOLD = Blood Oxygenation Level Dependent

• functional Magnetic Resonance Imaging

• Deoxyhemoglobin is paramagnetic and produces a reduced signal, oxyhemoglobin is weakly dimagnetic and doesn’t reduce the signal.

BOLD and Cerebral Blood Flow

BOLD and electro-physiology: correlation

Same area in V1 of cat, Kim DS (2004)

BOLD and electro-physiology: correlation

Single unit recording, cat V1, Kim 2004

What causes BOLD?

• The purpose of the increase in blood oxygenation is to feed neurons…

• …so, what makes a neuron hungry?

• (neurons can’t store much energy)

Vascular density

• Vascular density is proportional to synaptic density, not soma density

Hungry brainsWhite matter uses ¼ the energy of grey matter per unit volume

Attwell & Iadecola 2002

62% of mitochondria are in dendrites

Regulation of blood flow

Regulation of blood flow

• Is it feedback or feed forward?

Activity Uses energy

Vascular system must supply more energy

ActivityDirectly commands more blood flow

Regulation of blood flow

• Feedforward!

ActivityDirectly commands more blood flow

• Energy use does not directly increase blood flow…•…so how does tell CBF to increase?

Feed forward pro-active control

Monoamines and blood flow

• DA, NA and 5HT = vasoconstriction

• Cholinergic axons from BF = vasodilation

• This complicates neuropsychiatric studies

• e.g. schizophrenia, PD, ADHD

Localising fMRI

Cat scanner (!); Kim 2004

Correlation of BOLD and single unit

Kim 2004

Summation of BOLDBOLD

LFP

Single unit

Comparing different areas

• Different vasculature

• Different neuromodulatory control

• Different circuitry

• BOLD [X] > BOLD [Y] does not mean NEURAL ACTIVITY [X] > ACTIVITY [Y]

Comparing different subjects

What BOLD does not measure

• The output of an area

• Comparisons of activity between areas

• GABA ??????

What does contribute to BOLD

• Synaptic activity

• Local processing

• Sub-threshold neuromodulatory inputs

What does a blob in area X mean?

• X has changed its local activity

• Change of modulatory inputs arriving at X

• Change of inputs arriving at X

• (beware: the areas giving rise to the inputs to X may not produce a BOLD signal if their local synaptic activity levels remain constant)

References• Logothetis NK & Wandell BA (2004) Interpreting the BOLD signal Annu. Rev. Physiol

66:735-69

• Attwell D & Iadecola C (2002) The neural basis of functional brain imaging signals Trends in Neurosciences 25:621-625

• Kim DS et al (2004) Spatial relationship between neuronal activity and BOLD functional MRI NeuroImage 21:876-885