Statistical Parametric Mapping

1. 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

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

3. 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

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

5. T2* fMRI Signal HbO2 – Oxyhemoglobin Hbr - Deoxyhemoglobin

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

7. fMRI and Electrophysiology Logothetis et al, Nature 2001 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

8. Haemodynamic Response balloon model % -1 undershoot initial dip Buxton R et al. Neuroimage 2004

9. positive BOLD response 3 initial dip post stimulus undershoot 2 overshoot 1 Deoxyhemoglobin BOLD response, % 0 time BOLD signal stimulus • Initial dip 0.5-1sec • Overshoot peak 5-8 sec • + BOLD response 2-3% • Final undershoot variable fMRI Bold Response Model Figure 8.1. from textbook.

10. on stimulus off time image acquisition 14 10 6 2 -2 t value A BOLD Block Design Visual Study time voxel response 4.5 3 Signal [%] correlation predicted response 1.5 0 0 -1.5 0 20 40 60 80 100 120 140 160 180 Time [s] Bruce Pike, BIC at MNI.

11. 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.

12. 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.

13. 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.

14. 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. Mandeville et al., 1999 Figure 8.4. from textbook.

15. 511 keV + 511 keV Measurement of Cerebral Blood Flowwith 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) PET Method O-15 H20 Detre et al., 1992

16. inversion slab imaging plane Arterial Spin Labeling z (=B0) • 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 excitation blood y x inversion white matter = low perfusion Gray matter = high perfusion www.fmrib.ox.ac.uk/~karla/

17. 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.

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

19. 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.

20. 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.

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

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

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