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Blood oxygenation level dependent (BOLD) imaging is the standard technique used to generate images in functional MRI (fMRI) studies, and relies on regional differences in cerebral blood flow to delineate regional activity.
Blood flow in the brain is highly locally controlled in response to oxygen and carbon dioxide tension of cortical tissue. When a specific region of the cortex increases its activity in response to a task, the extraction fraction of oxygen from the local capillaries leads to an initial drop in oxygenated hemoglobin (oxyHb) and an increase in local carbon dioxide (CO2) and deoxygenated hemoglobin (deoxyHb). Following a lag of 2-6 seconds, cerebral blood flow (CBF) increases, delivering a surplus of oxygenated hemoglobin, washing away deoxyhemoglobin 1,2. It is this large rebound in local tissue oxygenation which is imaged.
The reason fMRI is able to detect this change is due to a fundamental difference in the paramagnetic properties of oxyHb and deoxyHb.
Deoxygenated hemoglobin is paramagnetic whereas oxygenated hemoglobin is not, and therefore the former will cause local dephasing of protons, and thus reduce the returned signal from the tissues in the immediate vicinity. Heavily T2* weighted sequences are used to detect this change, which is in the order of 1-5% 2.
There are a number of limitations of BOLD imaging (and all other techniques which image function by CBF):
- cerebral blood flow (CBF) is only an indirect marker of activity, rather than directly visualizing active cortex
- the smallest unit of brain that is able to have its blood flow individually regulated is in the order of millimeters in diameter
- CBF increases in response to increased activity and there is a 2-6 second lag
Additionally, there are a number of limitations related to imaging sequences themselves:
- T2* sequences are susceptible to field inhomogeneity due to bone-gas interface, hemosiderin/blood products, rapid flow in large veins, metal
- as the change detected is small (1-5%) even small movement artifacts can lead to poor images
History and etymology
The rationale behind the BOLD MRI technique dates back (ideally) to 1936, the year in which Linus Pauling published a scientific article on the magnetic properties of hemoglobin as a function of its state of oxygenation 3.
- 1. Moonen CT, Bandettini PA. Functional MRI. Springer Verlag. (1999) ISBN:3540642633. Read it at Google Books - Find it at Amazon
- 2. Stippich C, Blatow M. Clinical Functional MRI, Presurgical Functional Neuroimaging. Springer Verlag. (2007) ISBN:3540244697. Read it at Google Books - Find it at Amazon
- 3. Pauling L, Pauling CC, Pauling. The Magnetic Properties and Structure of Hemoglobin, Oxyhemoglobin and Carbonmonoxyhemoglobin. (1936) Proceedings of the National Academy of Sciences of the United States of America. doi:10.1073/pnas.22.4.210 - Pubmed