FMRI: What are we measuring?
Tzu-chen Yeh, Taipei Veteran General Hospital
Blood oxygenation level dependent (BOLD) fMRI probes the CBF and energy metabolism coupling to neural activity. Energy derived from the carbon flux of glial and neural cells restores ionic gradients and repackage neurotransmitter molecules. CBF brings oxygen/glucose and carry away waste metabolic products (CO2, heat). So, CBF coupled to neural activity with mechanisms not clearly understood. Delayed response of CBF relative to neuronal activity usually over-compensate metabolism. This form the base of BOLD, even there are several possible mechanisms for fMRI signal. OEF (oxygen extraction fraction, E) will decrease during activation, due to improportional increase of CBF. Deoxy-hemoglobin levels decrease in capillary and venous compartments. BOLD signal change has a delay of several seconds, and a very brief stimulation produced a BOLD hemodynamic change for several seconds.
Other transient features of BOLD response included (1) post-stimulation undershoot (PSU) lasting for tens of seconds and (2) early negative dip (END, corresponding to initial increased deoxyHb during activation from optical study in animal model). From present models of hemodynamic responses, the PSU and END may represent specific distribution of the uncoupling or mismatching between CBF and oxygen metabolism.
Models of the hemodynamics included following;
(1) oxygen limitation model (OLM) for mismatching of CBF and CMRO2: large increase in CBF is required to support the smaller increase in oxygen metabolism.
Evidences of OLM are derived from (a) at rest a large fraction of the delivered oxygen never leave the capillary, but nearly all oxygen enters tissue got metabolized; and (b) CBF increased by increased capillary velocity rather than opening new capillary (capillary recruitment).
(2) Balloon model for the CBV: CBV slowly response as compared to CBF.
Open questions of fMRI:
1. various delayed hemodymaic response perturbed the universal modeling.
2. components of hemodynamic response (END, PSU) might provide different specificity.
3. local variation of hemodynamics during activation needs to clarify.
4. specificity of gray matter detected by BOLD fMRI can be challenged.
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