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

2. Cerebral blood vessels Capillary beds extend into gray matter Arteries enter cortical surface perpendicularly Layer 1 Layer 6

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

4. Signal Pathway in BOLD fMRI Brain activity Oxyhemoglobin Deoxyhemoglobin Magnetic Susceptibility Glucose, O 2 consumptionblood volume, blood flow T2*, T2 fMRI Signal Oxy – diamagnetic Deoxy – paramagnetic M =  H (susceptibility constant =  )  Deoxy >  tissue  Oxy ~  tissue

5. T2* fMRI Signal HbO 2 – Oxyhemoglobin Hbr - Deoxyhemoglobin

6. From Neural Activity to fMRI Signal Neural activitySignallingVascular response Vascular tone (reactivity) Autoregulation Metabolic signalling BOLD signal glia arteriole venule B 0 field Synaptic signalling Blood flow, oxygenation and volume Complex relationship between change in neural activity and change in blood flow (CBF), oxygen consumption (CMRO 2 ) and volume (CBV). dendrite End bouton

7. fMRI and Electrophysiology Logothetis et al, Nature 2001 a. 24 sec stimulation b. 12 sec stimulation c. 4 sec stimulation LFP – local field potentials reflect dendritic currents MUA – multiunit activity SDF – single unit activity (?)

8. Haemodynamic Response Buxton R et al. Neuroimage 2004 balloon model % initial dip undershoot

9. fMRI Bold Response Model time BOLD response, % initial dip positive BOLD response post stimulus undershoot overshoot 1 2 3 0 stimulus Figure 8.1. from textbook. Initial dip0.5-1sec Overshootpeak 5-8 sec + BOLD response2-3% Final undershootvariable Deoxyhemoglobin BOLD signal

10. A BOLD Block Design Visual Study time voxel response 020406080100120140160180 -1.5 0 3 4.5 Time [s]  Signal [%] stimulus off on image acquisition time -2 2 6 14 10 t value 1.5 predicted response correlation 0 Bruce Pike, BIC at MNI.

11. Non-Linearity of BOLD Response  BOLD response vs. length of stimulation BOLD response during rapidly-repeated stimulation tsts  Block designs use stimulus and rest periods are that are long relative to BOLD response.

12. Graded BOLD Response Figure 8.2. from textbook. N=12 subjects. 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 %.

13. Model of Overshoot/Undershoot Figure 8.3. from textbook. 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

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

15. Measurement of Cerebral Blood Flow with PET or MRI (Arterial Spin Labeling - ASL) 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 ++ 511 keV PET Method O-15 H 2 0

16. Arterial Spin Labeling ASL IMAGE = IMAGE unlabeled – IMAGE labeled 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/ inversion slab imaging plane excitation inversion x y z (=B 0 ) blood white matter = low perfusion Gray matter = high perfusion

17. Hypercapnia, Perfusion, & BOLDResponses Figure 8.5. from textbook. Perfusion (CBF) and BOLD changes. 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 CMRO 2 – Cerebral Metabolic Rate of Oxygen Consumption Hypercapnia (increased CO 2 ) increases CBF w/o increasing oxygen demand (CMRO 2 ).

18. ASL interleaved with BOLD Figure 8.8. from textbook. Acquisition of CBF and BOLD data supports calculation of CMRO 2 using model equation.

19. Flow/Metabolism Coupling and the BOLD Signal Figure 8.9. from textbook. BOLD vs Perfusion (CBF) graded hypercapnia (dark circles) graded visual stimuli (different shapes) CMRO 2 vs Perfusion (CBF) perfusion has somewhat linear relationship with CMRO 2 derived from data in “a”

20. Model Based Images Figure 8.10. from textbook. a. M from model equation – predicts max BOLD signal potential b. BOLD – visual stimulation flashing checkerboard c. CBF (perfusion) d. CMRO 2 (oxygen compution rate)

21. Localization of Functional Contrast Perfusion Activation BOLD Activation Perfusion BOLD* *1.5T/Gradient Echo drainingvein

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

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