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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 Layer 1 Layer 6 • Capillary beds extend into gray matter • Arteries enter cortical surface perpendicularly 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 Signal Pathway in BOLD fMRI Brain activity Glucose, O2 consumption blood volume, blood flow Oxyhemoglobin Deoxyhemoglobin Oxy – diamagnetic Deoxy – paramagnetic Magnetic Susceptibility T2*, T2 fMRI Signal M = cH (susceptibility constant = c) cDeoxy> ctissue cOxy~ ctissue T2* fMRI Signal HbO2 – Oxyhemoglobin Hbr - Deoxyhemoglobin From Neural Activity to fMRI Signal Neural activity Signalling Vascular response Vascular tone (reactivity) Autoregulation Synaptic signalling BOLD signal Blood flow, oxygenation and volume arteriole B0 field glia Metabolic signalling End bouton dendrite venule Complex relationship between change in neural activity and change in blood flow (CBF), oxygen consumption (CMRO2) and volume (CBV). 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 Logothetis et al, Nature 2001 Haemodynamic Response balloon model % -1 Buxton R et al. Neuroimage 2004 initial dip undershoot fMRI Bold Response Model positive BOLD response • • • • Initial dip 0.5-1sec Overshoot peak 5-8 sec + BOLD response 2-3% Final undershoot variable 3 BOLD response, % 2 initial dip overshoot post stimulus undershoot 1 Deoxyhemoglobin BOLD signal 0 time stimulus Figure 8.1. from textbook. A BOLD Block Design Visual Study on stimulus off time image acquisition time voxel response 14 4.5 6 correlation 2 0 Signal [%] 10 3 predicted response 1.5 0 -2 t value -1.5 0 Bruce Pike, BIC at MNI. 20 40 60 80 100 120 140 160 180 Time [s] 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 are 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 CBF rapid CBV slow In rat experiments TC for CBV 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) PET orPET SPECT arterial labeling MRI PERFUSION Steady State Method Steady State Method Method keV 511 decay imaging slice control labeling T1 relaxation + 511 keV arterial spin labeling 15 O infusion O-15 H 0 2 or inhalation • 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) excitation y inversion slab blood x inversion imaging plane • ASL IMAGE = IMAGEunlabeled – IMAGElabeled • • • • white matter = low perfusion Gray matter = high perfusion 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, & BOLDResponses 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. ASL interleaved with BOLD Acquisition of CBF and BOLD data supports calculation of CMRO2 using model equation. 1/ CMRO2 BOLD / BOLD 0 1 CMRO2,0 M Figure 8.8. from textbook. 1 / CBF CBF 0 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 BOLD* *1.5T/Gradient Echo BOLD Activation draining vein ASL Perfusion fMRI vs. BOLD Improved Intersubject Variability vs. BOLD Aguirre et al., NeuroImage 2002 Single Subject Group (Random Effects) Physiological Basis of fMRI behavior neural function disease biophysics*** metabolism BOLD fMRI ***BOLD contrast includes contributions from biophysical effects such as magnetic field strength homogeneity and orientation of vascular structures. ASL CBF MRI blood flow ASL fMRI measures changes in CBF directly, and hence measured signal changes may be more directly coupled to neural activity