0205
Ultra high field BOLD measurements combined with simultaneous determination of blood oxygenation and blood volume by optical imaging1Magnetic Resonance Center, Max Planck Institute for Biological Cybernetics, Tübingen, Germany, 2Biomedical Magnetic Resonance, University of Tübingen, Tübingen, Germany
Synopsis
To disentangle the different parameters contributing to the BOLD effect, a combined setup for intrinsic optical imaging and ultra high field fMRI in rats was designed, using a magnetic field compatible, high sensitivity camera and professional optical components. By illumination of the brain surface with light in four different wavelengths, oxygenation and CBV was observed concurrently with fMRI during forepaw stimulation. Simultaneous measurement of those parameters can help to better understand the BOLD effect and to add additional value to both optical imaging and fMRI experiments.
Introduction
The BOLD effect arises as a complex mixture of changes in blood oxygenation, volume and flow. To better understand the BOLD effect and the underlying hemodynamic coupling mechanisms, a simultaneous measurement of those parameters and BOLD would be necessary. Optical imaging (OI) of intrinsic signals is a technique that makes it possible to quantitatively determine changes in blood oxygenation and volume separately. By concurrently acquiring OI and BOLD data at high spatial and temporal resolutions, we expect to improve our understanding of the formation of the BOLD effect and contribute to an improved analysis of fMRI experiments. With a combination of a high sensitivity optical imaging setup with an ultra high field MR scanner, we are able to simultaneously acquire images with both modalities with high quality and resolution.Methods
Lister hooded rats were anaesthetized with urethane and the skull above the somatosensory cortex was exposed. A dental drill was used to thin the skull to translucency, allowing an observation of the brain surface. To obtain both fMRI and OI images without any compromises in image quality compared to experiments performed separately, a tailor-made, magnetic field proof, scientific CMOS-camera was placed into a 14.1 T magnet. A set of commercially available, high-quality objectives were carefully stripped of all metallic parts and used to observe the brain surface via a prism. The brain was illuminated by light in four different wavelengths (465 nm, 530 nm, 595 nm, 630 nm) alternately, transmitted into the magnet by optical fibers. Home written software and three Arduino microcontrollers were used to synchronize MR-acquisition, OI recordings, stimuli and illumination. A small NMR surface coil just above the somatosensory cortex was used for anatomical and functional imaging. The complete setup is shown in Fig. 1.
The somatosensory cortex of the rat was activated by electrical forepaw stimulation with varying parameters and was observed by OI (one image every 50 ms; 200 ms for one cycle of four illumination wavelengths) and fMRI (four slices parallel to brain surface, 80×80 voxels, FOV 22×22 mm2, TR = 0.5 s) simultaneously. The fMRI data was analyzed by SPM12 to identify activated brain regions. OI data acquired with the different illumination wavelengths was combined to quantitatively determine concentration changes in oxygenated and deoxygenated hemoglobin, where differences in the optical path lengths between the four wavelengths were taken into account, using published path length data1. OI and fMRI images were superimposed, taking venous structures, which are visible in both OI and MRI images, as markers to coregister the images of both modalities. fMRI and OI time courses from the activated region (as determined with SPM) were extracted.
Results
OI and fMRI images with excellent quality were acquired. Venous structures were clearly visible with both modalities and helped to superimpose the different images. Images showing oxygenation and CBV changes and the area of significant BOLD response are shown in Fig. 2. The activation timecourses from fMRI and OI for a 3 s stimulus with 9 Hz and 2.5 mA are plotted in Fig. 3. Fig. 4 shows signal changes caused by activation with different stimulus durations between 1s and 5 s.Discussion
Concurrent MRI and OI can potentially help to improve our understanding of the BOLD effect and the hemodynamic processes that contribute to the fMRI signal. A previous approach applied an endoscope to transport the optical signals from the magnet to be recorded by a conventional camera2. By using a specially designed camera, which combines high sensitivity with full compatibility with the magnetic field, and high-performance optical components, we are able to obtain images from inside the magnet without losses in quality compared to those acquired in standard OI experiments. The combination with ultra-high field MRI ensures also a high fMRI image quality and spatial and temporal resolution. In addition to fMRI, anatomical imaging could be used to enhance the OI experiments, e.g. by locating ascending arteries.Conclusion
Combining intrinsic optical imaging with fMRI can help to disentangle the different factors contributing to the BOLD effect and yield important information to enhance both OI and fMRI experiments. Furthermore, the developed setup can be combined with other optical techniques to measure further neuroscientific parameters at the same time.Acknowledgements
No acknowledgement found.References
1. Ma, Y., et al. (2016). "Wide-field optical mapping of neural activity and brain haemodynamics: considerations and novel approaches." Philos Trans R Soc Lond B Biol Sci 371(1705).
2. Kennerley, A. J., et al. (2005). "Concurrent fMRI and optical measures for the investigation of the hemodynamic response function." Magnetic Resonance in Medicine 54(2): 354-365.
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