Concurrent intrinsic optical imaging and fMRI at ultra-high field using magnetic field proof optical components

Although being applied in thousands of neuroscientific studies, the BOLD effect and the underlying neurovascular coupling are still a question of intense research. A major challenge is the complex generation of the BOLD effect as a combination of several interacting contributions, mainly the change in cerebral blood volume (CBV), cerebral blood flow (CBF) and blood oxygenation, which have different temporal and spatial distributions. Intrinsic optical imaging (IOI) 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 by bringing a magnetic field proof, high sensitivity scientific CMOS camera, including fully professional optics, into the 14.1 T scanner. The somatosensory cortex of anaesthetized rats is illuminated by light from LEDs with four different wavelengths transmitted by optical fibers and is observed by the optical imaging setup through the thinned skull. Brain activity is evoked by electrical forepaw stimulation. Concentration changes in oxygenated and deoxygenated hemoglobin are calculated using the differential pathlength approach. FMRI images are acquired simultaneously with slice thickness of 0.5 mm, comparable to the penetration depth of the used wavelengths. Optimized anatomical MR images visualizing veins or arteries and high-resolution fMRI and point-spread function-based distortion correction allow accurate colocalization of optical and MR images and make it possible to separate signals from different anatomical origins like veins, arteries and tissue compartments containing capillaries. The concurrent acquisition of fMRI and optical imaging data makes it possible to quantitatively correlate the different hemodynamic parameters and their effect on the fMRI signal, allowing us to closely investigate the generation of the BOLD effect and hemodynamic processes during neuroactivation.

Modifications for obtaining different optical or MRI contrasts are easily possible. Additional filters, inserted into the light path, allow us to extend the setup to fluorescence imaging techniques like calcium imaging. Measuring intracellular calcium concentration as an direct indicator for neuronal activation concurrently with intrinsic hemodynamic and BOLD signals can further enhance the toolbox available for investigating the processes involved in neurovascular coupling.



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