Absolute Beginners Guide to Neuroimaging Methods : fMRI

Functional magnetic resonance imaging (fMRI) is the primary means used to measure brain function non-invasively in humans, because of the advantages it offers in terms of high spatiotemporal resolution and localization as compared to other non-invasive modalities (e.g. EEG, MEG). Since its emergence about 20 years ago, it has rapidly evolved into the mainstay of functional neuroimaging for neuroscience and in the clinic, currently yielding more than 7 peer reviewed manuscripts per day. fMRI measures brain function indirectly via hemodynamic changes that arise from neuronal activation. The physiologic mechanism is based on the fact that neuronal (and glial) activity consumes energy which is mainly met via oxidative metabolism, translating to a local increase in oxygen consumption and cerebral metabolic rate of oxygen (CMRO2). As oxygen is provided by the blood, this triggers a local increase in cerebral blood flow (CBF) and cerebral blood volume (CBV) in the target region (1-4). This hemodynamic response occurs via an intricate and highly organized vascular tree of several groups of vessels arranged according to their diameter (~5-100 μm) and cortical depth they penetrate (5). In simple terms, oxygenated blood flows from arteries at the cortical pial surface toward the capillary bed within gray matter, where oxygen exchange takes place, and deoxygenated blood is then passively drained by intra-cortical veins toward the pial surface (6-7). Notably, the temporal evolution of the hemodynamic response is much slower than that of the underlying neuronal response (sec vs. msec). Changes in CBF occur at the arterial side of the vasculature, CBV changes involve both the arterial and venous side, and changes in blood oxygenation are evident at the venous side that drains from active neuronal sites. Several fMRI techniques exist that target these different aspects of the hemodynamic response; for example perfusion-based arterial-spin-labeling (ASL; e.g. (8)) can be used to assess CBF, the vascular space occupancy technique (VASO; (9)) can be used to assess CBV, and blood-oxygenation-leveldependent (BOLD; (10)) based techniques can be used to assess changes in blood oxygenation. By far, the most widely used fMRI technique is based on the BOLD contrast because of the higher sensitivity afforded as compared to other fMRI techniques. BOLD is an endogenous contrast that capitalizes on the magnetic properties of deoxygenated hemoglobin (deoxy-Hb) in the blood, specifically in the venous side of the vasculature (capillaries, venules, intracortical veins, pial vessels). Deoxy-Hb is paramagnetic and causes a distortion of the magnetic field inside (intra-vascular) and around (extra-vascular) the vessels which alters the T2 and T2* decay of the MR signal in that region. The mechanism is somewhat counter-intuitive: with increases in neuronal activity there is an oversupply of oxygenated blood.