Concurrent Intrinsic Optical Imaging and fMRI in the Rat at 14.1 T
Quantifying the BOLD effect and its physiological contributions
Though it is used in a large number of neuroscientific studies, the BOLD effect, arising due to a complex interplay of changes in blood volume, blood oxygenation and blood flow, is still not completely understood. Intrinsic optical imaging can help to disentangle the different contributions, being able to measure changes in oxygenation and blood volume separately and quantitatively. While many studies have observed brain activation with intrinsic optical imaging and related the resulting data to fMRI studies, to determine a quantitative relationship, simultaneous measurements with both modalities are necessary.
We have developed a setup to measure both intrinsic optical imaging and fMRI simultaneously and without compromises in resolution or image quality in either modality by bringing a magnetic field proof, high sensitivity scientific CMOS camera, including fully professional optics, into the 14.1 T scanner. Illumination with light in four wavelengths allows us to follow changes in blood volume and oxygenation while running fMRI experiments.
Anatomical gradient echo MR-image with overlaid optical and fMRI data. The good visibility of the veins in both MR- and optical images allow for an accurate colocalization of the two modalities. Activation-induced changes in the concentrations of oxygenated and deoxygenated blood are mainly colocalized with the veins. CBV changes mainly correspond to arteries.
In the experiments, anaesthetized rats are submitted to electrical forepaw stimulation with varying intensity, duration or pulse frequency. The somatosensory cortex is observed by the optical imaging setup through the thinned skull and illuminated by light with four wavelengths successively. Simultaneously, fMRI images from slices parallel to the brain surface are acquired, using a distortion correction technique. MRI venograms are used to align MR and optical images, and the differential pathlength approach is used to calculate the concentration changes in oxygenated and deoxygenated hemoglobin.
Time course of BOLD signal change and concentrations of oxygenated (HbO) and deoxygenated (HbR) blood and cerebral blood volume (CBV) caused by a 3 s forepaw stimulation.
This approach combines the advantages of intrinsic optical imaging – high sensitivity, high temporal and spatial resolutions, quantitative character and separate determination of changes in HbO and HbR – with those of fMRI to improve the understanding and modelling of the BOLD effect. Further information will become available by adding an optical measurement of the intracellular Ca2+-concentration using a genetically encoded calcium indicator, which can relatively easily be added to the current protocol.