BOLD Imaging

An Introduction to MRI Physics and Analysis

Michael Jay Schillaci, PhDMonday, February 25, 2008

Overview Neurophysiology

The brain’s vascular system Neurons, dendrites and pumpsEnergy in the brain

BOLD Imaging Source of BOLD SignalThe Hemodynamic responseBOLD Artifacts

Neurophysiology

Duvernoy, H. M., Delon, S., & Vannson, J. L. (1981). Cortical blood vessels of the human brain. Brain Research Bulletin,

7(5), 519-579.

Arteries (1-25mm)Arterioles (10 - 300 microns)precapillary sphinctersCapillaries (5-10 microns)Venules (8-50 microns)Veins

(anastomosis of internal carotids and basilar

artery)

ACA – Medial cortex

MCA – Anterolateral cortex

PCA – Posterior temporal and occipital lobes

Sinus. n. An separation of the dura mater in

which blood drains into the venous system.

Distribution of vascularization - occurs across cortical layers

Capillary structure

Oxygen (via

hemoglobin)

Glucose

Facts about energy supply to brain

30-50 μmol/g/min of ATP for awake brain

10 μmol/g/min of ATP for comatose brain

Information processing accounts for >75% of ATP consumption

54mL/min of blood for each 100 g of brain tissue

Brain is ~3% of body weight, but demands 15-20% of blood flow and ~20% of blood oxygen

There are two primary types of information flow in the CNS:

1) Signaling via action potentials (axonal activity) and

2) Integration via dendritic activity

Action potential

Depolarization opens CA2+ channels

Vesicles fuse with presynaptic membrane

Neurotransmitter release

Neurotransmitters open ion channels on postsynaptic membrane

Change in potential

IPSP or EPSP

Energy Demands of Integration/SignalingFollowing activity, neurons require energy to restore concentration gradients of key

ions.Sodium-Potassium

pump takes sodium out of the cell while

bringing potassium into the cell.

Note that for action potentials, the

movement of ions is along gradients.

Key concept: activity of neurons does not itself require energy; restoring membrane potentials afterward does.

BOLD Imaging

BOLD - Endogenous Contrast Blood Oxyenation Level Dependent Contrast

dHb is paramagnetic, Hb is less Susceptibility of blood increases linearly with oxygenation BOLD subject to T2* criteria

Oxygen is extracted from capillaries Arteries are fully oxygenated Venous blood has increased proportion of dHb Difference between Hb and dHb states is greater for veins Therefore BOLD is result of venous blood changes

Sources of the BOLD Signal

Neuronal activity Metabolism

Blood flow

Blood volume

[dHb]BOLDsignal

BOLD is a very indirect measure of activity…

Facts about blood flow Aorta peak flow: 90 cm/s Internal carotid flow: ~ 40 cm/s Smaller arteries: ~10-250 mm/s Capillaries: ~ 1 mm/s Venules and small veins: ~10-250 mm/s

Change in arteriole dilation as a function of distance from active neurons

Iadecola, Nature Reviews Neuroscience, 2004

How does the vascular system respond to neuronal activity?

Iadecola, Nature Reviews Neuroscience, 2004

Physiological data suggests that blood flow

changes may be associated with

preponderance of dendritic activity, but

disconnections are possible.

Neuronal Origins of BOLD

Adapted from Logothetis et al. (2002)

BOLD response predicted by dendritic activity (LFPs)

Increased neuronal activity results in increased MR (T2*) signal

LFP=Local Field Potential; MUA=Multi-Unit Activity; SDF=Spike-Density Function

BASELINE ACTIVE

Hemoglobin and Magnetism The Hemoglobin (Hb) Molecule

An organic molecule containing four heme groups (with iron in each) and globular protein (globin).

Oxygen Characteristics Oxygen bound - oxyhemoglobin (Hb) No oxygen bound - deoxyhemoglobin (dHb)

Magnetic Properties Hb is diamagnetic - no dipole dHb is paramagnetic - slight dipole

Oxygen and Field Strength Apply magnetic field to brain Blood oxygen level differs

dHb is paramagneticLocal field increased

Hb diamagneticLocal field decreased

Blamire et al., 1992This was the first event-related fMRI study. It used both blocks and pulses of visual stimulation.

Hemodynamic response to long stimulus durations.

Hemodynamic response to short stimulus durations.

Gray Matter

White matter

Outside Head

fMRI and Contrast Endogenous Mechanism

Blood deoxygenation affects T2 Recovery

Increasing Blood Oxygenation Level

Dec

reas

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Re

laxa

tion

Tim

e

T2

T1

Basic Form of Hemodynamic Response

Initial Dip (Hypo-oxic Phase)

Transient increase in oxygen consumption, before change in blood flow Menon et al., 1995; Hu, et al., 1997

Shown by optical imaging studies Malonek & Grinvald, 1996

Smaller amplitude than main BOLD signal 10% of peak amplitude (e.g., 0.1% signal change)

Potentially more spatially specific Oxygen utilization may be more closely associated with neuronal activity than perfusion

response

Early Evidence for the Initial Dip

CA B

Menon et al, 1995

Why is the initial dip controversial?

Not seen in most studies Spatially localized to Minnesota May require high field

Increasing field strength increases proportion of signal drawn from small vessels

Of small amplitude/SNR; may require more signal Yacoub and Hu (1999) reported at 1.5T

May be obscured with large voxels or ROI analyses May be selective for particular cortical regions

Yacoub et al., 2001, report visual and motor activity Mechanism unknown

Probably represents increase in activity in advance of flow But could result from flow decrease or volume increase

Yacoub et al., 2001

Negative BOLD response caused by impaired oxygen supply

Subject: 74y male with transient ischemic attack (6m prior) Revealed to have arterial

occlusion in left hemisphere

Tested in bimanual motor task

Found negative bold in LH, earlier than positive in right

Rother, et al., 2002

The Hemodynamic Response Lags Neural Activity

Experimental Design

Convolving HDR

Time-shifted Epochs

Introduction of Gaps

The fMRI Linear Transform

Boynton et al., 1996

Varied contrast of checkerboard bars as well as their interval (B) and duration (C).

Boynton, et al, 1996

Refractory Periods

Definition: a change in the responsiveness to an event based upon the presence or absence of a similar preceding eventNeuronal refractory periodVascular refractory period

Dale & Buckner, 1997

Responses to consecutive presentations of a stimulus add in a “roughly linear” fashion

Subtle departures from linearity are evident

Intra-Pair Interval (IPI)

Inter-Trial Interval(16-20 seconds)

6 sec IPI

4 sec IPI

2 sec IPI

1 sec IPI

Single-Stimulus

Huettel & McCarthy, 2000

500 ms duration

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Hemodynamic Responses to Closely Spaced Stimuli

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“Rough Linearity”

Time since onset of second stimulus (sec)

Sig

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hang

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T2*: fMRI Signal is an Artifact

BOLD artifacts fMRI is a T2* image – we will have all the artifacts that a

spin-echo sequence attempts to remove. Dephasing near air-tissue boundaries (e.g., sinuses)

results in signal dropout.

BOLDNon-BOLD

Neuro-Vascular coupling