BOLD Imaging An Introduction to MRI Physics and Analysis Michael Jay Schillaci, PhD Monday, February 25, 2008
Overview • Neurophysiology • The brain’s vascular system • Neurons, dendrites and pumps • Energy in the brain • BOLD Imaging • Source of BOLD Signal • The Hemodynamic response • BOLD Artifacts
Arteries (1-25mm)Arterioles (10 - 300 microns)precapillary sphinctersCapillaries (5-10 microns)Venules (8-50 microns)Veins Duvernoy, H. M., Delon, S., & Vannson, J. L. (1981). Cortical blood vessels of the human brain. Brain Research Bulletin, 7(5), 519-579.
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.
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: • Signaling via action potentials (axonal activity) and • 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/Signaling Following 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 - 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
Blood flow Metabolism Neuronal activity BOLD signal [dHb] Blood volume Sources of the BOLD Signal 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? Physiological data suggests that blood flow changes may be associated with preponderance of dendritic activity, but disconnections are possible. Iadecola, Nature Reviews Neuroscience, 2004
Neuronal Origins of BOLD 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 Adapted from Logothetis et al. (2002)
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 paramagnetic • Local field increased • Hb diamagnetic • Local field decreased
Blamire et al., 1992 This was the first event-related fMRI study. It used both blocks and pulses of visual stimulation. Gray Matter Hemodynamic response to long stimulus durations. White matter Hemodynamic response to short stimulus durations. Outside Head
fMRI and Contrast • Endogenous Mechanism • Blood deoxygenation affects T2 Recovery T2 Decreasing Relaxation Time T1 Increasing Blood Oxygenation Level
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 C A 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
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 Negative BOLD response caused by impaired oxygen supply Rother, et al., 2002
Convolving HDR Time-shifted Epochs Introduction of Gaps The Hemodynamic Response Lags Neural Activity Experimental Design
Boynton et al., 1996 Varied contrast of checkerboard bars as well as their interval (B) and duration (C).
Refractory Periods • Definition: a change in the responsiveness to an event based upon the presence or absence of a similar preceding event • Neuronal refractory period • Vascular 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 500 ms duration Huettel & McCarthy, 2000
“Rough Linearity” Signal Change over Baseline(%) Time since onset of second stimulus (sec)
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. BOLD Non-BOLD