BOLD signal dependence on blood flow and metabolism. Outline

Transcription

1 BOLD signal dependence on blood flow and metabolism R. Hoge, MGH NMR Center Outline physiological events accompanying neuronal activation factors affecting BOLD signal sensitivity BOLD response dynamics

2 Physiological Events Accompanying Neuronal Activation information processing in neurons electrical chemical maintenance of membrane potential vascular neurotransmitter receptors (dopamine, NO) metabolism glucose O neurotransmitter recycling (glutamate) local and long range neural projections to vasculature blood flow arteriolar resistance metabolic byproducts (CO, H+) hydrostatic pressure, vascular smooth muscle tone blood volume arterial venous Stimulus-driven glucose uptake: DG autoradiography during visual stim. in monkey tootell et al. 988

3 Deoxygenated blood attenuates T * -weighted MR images O MRI volume element decrease of venous dhb during increased perfusion: O

4 Cerebral blood flow is affected by both systemic and focal influences: stimulation + hypercapnia hypercapnia only 5 stimulation + hypocapnia stimulation only Perfusion (% increase) Perfusion (% change) Outline physiological events accompanying neuronal activation factors affecting BOLD signal sensitivity BOLD response dynamics

5 Factors affecting BOLD signal physiology blood flow, metabolism, blood volume equipment magnetic field value pulse sequence gradient-echo vs. spin-echo echo time resolution Oxidative metabolism attenuates the BOLD signal: CBF BOLD CBF (% increase) BOLD (% increase) hypercapnia visual stimulation 6 8 N=

6 CBF-CMRO CMRO coupling determines the BOLD signal during activation: 4 CMRO (% increase) BOLD (% increase) Perfusion (% increase) 5 Perfusion (% increase) Spatial patterns of BOLD, flow, and metabolism: flow 8 6 % model for spatial pattern of BOLD contrast BOLD sensitivity M [dhb] 5 BOLD 4 - % CMRO % % CMRO imaging CMRO quantitation supported by PET imaging (Marret et al.)

7 Images of %BOLD %BOLD show different spatial patterns than BOLD statistical maps: BOLD percent change 4 % statistical map + p=.5 t= p=.5 flow - % t= Systemic vasoactive effects (respiratory, drug) are amplified in BOLD imaging: BOLD flow Activation (~%) Activation (~5%) Global (~5%) Global (~%) due to lack of metabolic signal attenuation during systemically driven flow increases

8 If there are stimulus-correlated systemic effects,, flow contrast will provide much higher specificity than BOLD visual stim, BOLD visual stim, Flow + p=.5 visual stim + CO BOLD visual stim + CO Flow t= - Outline physiological events accompanying neuronal activation factors affecting BOLD signal sensitivity BOLD response dynamics

9 Temporal Response Waveforms initial dip overshoot and undershoot delayed CBV effects stimulus-dependent response waveforms Initial deoxyhemoglobin surge (fmri initial dip) Shtoyerman, Grinvald et al. attributed to early metabolic response appears to be highly spatially localized may be idiosyncrasy associated with specific visual input and/or anesthetic state

10 BOLD overshoot in V: BOLD (% change) signal averages 5 Perfusion overshoot in V: Perfusion (% change) signal averages

11 Slow-onset onset CBV response (rat forepaw stimulation) 6 CBF CBV % change - 6 time (sec) Mandeville et al. MRM 999 BOLD response waveforms for different stimuli at graded contrast levels: N= not all patterns produced BOLD overshoot contrast-sensitivity markedly different BOLD (% change) no overshoot no overshoot overshoot

12 Frequency-dependent step responses in V BOLD (% change) 7 min. stimulation - 5 Response waveforms in auditory areas during high-frequency noise bursts Heschl's Gyrus Superior Temporal Gyrus 6 6 courtesy of Mike Harms

13 Practical Questions what does BOLD signal mean, in physiological terms? what factors affect BOLD sensitivity to hemodynamic changes? how can I compare BOLD responses within regions (different conditions) across regions More practical Questions how do temporal response waveforms relate to underlying neurophysiology? what features of the BOLD response are general, and which are idiosyncratic? dips, over/undershoots, offset responses what factors affect the specificity of BOLD contrast as a marker for neuronal activation? gross regional specificity, high spatial resolution