Statistical Parametric Mapping Lecture 2 - Chapter 8 Quantitative Measurements Using fMRI BOLD, CBF, CMRO2 Textbook: Functional MRI an introduction to methods, Peter Jezzard, Paul Matthews, and Stephen Smith Many thanks to those that share their MRI slides online

Cerebral blood vessels Capillary beds extend into gray matter Arteries enter cortical surface perpendicularly Layer 1 - outer Layer 6 - inner

Signal Pathway in BOLD fMRI Brain activity Glucose, O2 consumption blood volume, blood flow Oxyhemoglobin Deoxyhemoglobin Oxy – diamagnetic (weak) Deoxy – paramagnetic (strong) M = cH (susceptibility constant = c) Deoxy> ctissue Oxy~ ctissue Magnetic Susceptibility T2*, T2 fMRI Signal

T2* fMRI Signal HbO2 – Oxyhemoglobin Hbr - Deoxyhemoglobin

From Neural Activity to fMRI Signal Signalling Vascular response Vascular tone (reactivity) Autoregulation Metabolic signalling BOLD signal glia arteriole venule B0 field Synaptic signalling Blood flow, oxygenation and volume End bouton dendrite Complex relationship between change in neural activity and change in blood flow (CBF), oxygen consumption (CMRO2) and volume (CBV).

Neuron’s General Structure ~50,000 neurons per cubic mm ~6,000 synapses per neuron ~10 billion neurons & ~60 trillion synapses in cortex input - dendrites & soma processing - throughout output - axon Structural variety of neurons

fMRI and Electrophysiology * LFP – local field potentials reflect dendritic currents MUA – multiunit activity SDF – single unit activity a. 24 sec stimulation b. 12 sec stimulation c. 4 sec stimulation Visual cortex Monkey Rotating checkerboard Logothetis et al, Nature 2001

Haemodynamic Response balloon model Functional contrast (and what each is good for) BOLD (blood oxygenation level dependent) T2 and T2* Perfusion (arterial spin labelling) - more quantitative but lower SNR Cerebral blood volume VASO, vascular space occupancy Functional Spectroscopy % -1 initial dip undershoot Buxton R et al. Neuroimage 2004

fMRI Bold Response Model time BOLD response, % initial dip positive BOLD response post stimulus undershoot overshoot 1 2 3 stimulus Initial dip 0.5-1sec Overshoot peak 5-8 sec + BOLD response 2-3% Final undershoot variable Deoxyhemoglobin BOLD signal Figure 8.1. from textbook.

A BOLD Block Design Visual Study stimulus off on image acquisition time time voxel response -2 2 6 14 10 t value 4.5 3 Signal [%] correlation 1.5 predicted response -1.5 20 40 60 80 100 120 140 160 180 Time [s] Bruce Pike, BIC at MNI.

Non-Linearity of BOLD Response BOLD response vs. length of stimulation t 2t BOLD response during rapidly-repeated stimulation ts Block designs use stimulus and rest periods that are long relative to BOLD response.

Graded BOLD Response Graded change in signal for a) BOLD and b) perfusion (CBF). 3 minute visual pattern stimulation with different luminance levels. Note max BOLD change of 2-3 % and max CBF change of 40-50 %. Figure 8.2. from textbook. N=12 subjects.

Model of Overshoot/Undershoot Models of waveform for a) BOLD and b) perfusion (CBF) change. Constant stimulation 50-250 sec. Overshoot more pronounced in BOLD waveform slow adjustment of CBV (Mandeville et al., 1999) Undershoot might be due to same effect Figure 8.3. from textbook.

Perfusion vs. Volume Change 30 second stimulation 3-second intervals DCBF rapid DCBV slow In rat experiments TC for DCBV similar to that for BOLD overshoot. Figure 8.4. from textbook. Mandeville et al., 1999

Measurement of Cerebral Blood Flow with PET or MRI (Arterial Spin Labeling - ASL) + 511 keV PET Method O-15 H20 Uses magnetically labeled arterial blood water as an endogenous flow tracer Potentially provide quantifiable CBF in classical units (mL/min per 100 gm of tissue) Detre et al., 1992

Arterial Spin Labeling z (=B0) inversion slab imaging plane excitation blood y x inversion white matter = low perfusion Gray matter = high perfusion ASL IMAGE = IMAGEunlabeled – IMAGElabeled Mostly use inversion (IR) labeling Labeled blood water extracted from capillaries T1 of blood is long compared to tissues Flow (perfusion) not dependent on local susceptibility www.fmrib.ox.ac.uk/~karla/

Hypercapnia, Perfusion, & BOLD Responses CMRO2 – Cerebral Metabolic Rate of Oxygen Consumption Hypercapnia (increased CO2) increases CBF w/o increasing oxygen demand (CMRO2). Response with graded hypercapnia (GHC thin line) and graded visual stimulation (GVS). Four levels in this study. BOLD response similar to CBF response to hypercapnia BOLD response attenuated relative to CBF during aerobic stimulation Figure 8.5. from textbook. Perfusion (CBF) and BOLD changes.

Relative BOLD vs. Relative CBF M is max possible BOLD signal change a is CBV-CBF coupling constant (0.38 for graphs) b is deoxy attenuating power (1.5 for graphs) Figure 8.6. from textbook.

ASL interleaved with BOLD Acquisition of CBF and BOLD data supports calculation of CMRO2 using model equation. Figure 8.8. from textbook.

Flow/Metabolism Coupling and the BOLD Signal BOLD vs Perfusion (CBF) graded hypercapnia (dark circles) graded visual stimuli (different shapes) CMRO2 vs Perfusion (CBF) perfusion has somewhat linear relationship with CMRO2 derived from data in “a” Figure 8.9. from textbook.

Model Based Images a. M from model equation – predicts max BOLD signal potential b. BOLD – visual stimulation flashing checkerboard c. CBF (perfusion) d. CMRO2 (oxygen compution rate) Figure 8.10. from textbook.

Localization of Functional Contrast Perfusion Perfusion Activation draining vein BOLD Activation BOLD* *1.5T/Gradient Echo

Group (Random Effects) ASL Perfusion fMRI vs. BOLD Improved Intersubject Variability vs. BOLD Aguirre et al., NeuroImage 2002 Group (Random Effects) Single Subject

Physiological Basis of fMRI behavior neural function disease biophysics*** metabolism BOLD fMRI ASL CBF MRI ***BOLD contrast includes contributions from biophysical effects such as magnetic field strength homogeneity and orientation of vascular structures. blood flow ASL fMRI measures changes in CBF directly, and hence measured signal changes may be more directly coupled to neural activity