Whole brain high-resolution functional imaging at ultra high magnetic fields: an application to the analysis of resting state networks

Abstract

Whole-brain functional magnetic resonance imaging (fMRI) allows measuring brain dynamics at all brain regions simultaneously and is widely used in research and clinical neuroscience to observe both stimulus-related and spontaneous neural activity. Ultrahigh magnetic fields (7T and above) allow functional imaging with high contrast-to-noise ratios and improved spatial resolution and specificity compared to clinical fields (1.5T and 3T). High-resolution 7T fMRI, however, has been mostly limited to partial brain coverage with previous whole-brain applications sacrificing either the spatial or temporal resolution. Here we present whole-brain high-resolution (1, 1.5 and 2mm isotropic voxels) resting state fMRI at 7T, obtained with parallel imaging technology, without sacrificing temporal resolution or brain coverage, over what is typically achieved at 3T with several fold larger voxel volumes. Using Independent Component Analysis we demonstrate that high resolution images acquired at 7T retain enough sensitivity for the reliable extraction of typical resting state brain networks and illustrate the added value of obtaining both single subject and group maps, using cortex based alignment, of the default-mode network (DMN) with high native resolution. By comparing results between multiple resolutions we show that smaller voxels volumes (1 and 1.5mm isotropic) data result in reduced partial volume effects, permitting separations of detailed spatial features within the DMN patterns as well as a better function to anatomy correspondence.

Figure 1. Summary of the analysis of 7T anatomical images

a) T₁ weighted (left), Proton Density weighted (center) and unbiased T₁ data (right) of one representative transversal slice of one exemplary subject. b) Single subject cortex segmentation results: white/gray matter border projected on one representative transversal slice of the unbiased T₁ data (left); single subject 3D mesh representing the left hemisphere of one selected subject (center); projection of the single subject left hemisphere to a spherical representation (right) to be used for cortex based alignment. c) Cortex based alignment of the four analyzed subjects: curvature representing gyri and sulci of four subject projected to a spherical representation and superimposed after smoothing (i.e. initial step of the cortex based alignment procedure) (left); reconstructed left hemisphere resulting from the mean curvature of four subjects after cortex based alignment (center); inflated representation of the mean left hemisphere (right).

Figure 2

Three exemplary slices of single subject functional data: 1 mm isotropic resolution (left), 1.5 mm isotropic resolution (center) and 2 mm isotropic resolution (right). Note the higher level of distortions due to partial volume in the frontal cortex of the 2 mm isotropic data (yellow arrow).

Figure 3

Group ICA results for low-resolution (3 mm isotropic) analysis of the data acquired with 1.5 mm isotropic voxels. Components representing the: a) default mode network; b) primary visual network; c) sensory-motor network; d) executive network; e) secondary auditory network; f) primary auditory network; g) secondary visual network; e) imagery network; are overlaid on the average anatomical T₁ data.

Figure 4. Selection procedure of high-resolution data independent components

a) Template (red transparent) of Default Mode Network obtained from the analysis (group ICA) of the 2 mm data resampled at 3 mm isotropic and spatially smoothed with a Gaussian kernel of FWHM = 6 mm. b) Results of spatial correlation analysis with the DMN template for the ICs obtained from the 1 mm (left), 1.5 mm (center) and 2 mm (right) data resampled at 1 mm isotropic and smoothed with a FWHM = 2 mm. Correlations across the four subjects (median 25^th and 75^th percentile) are shown together with a transverse slice of the mean across subjects for the best two ICs.

Figure 5

Single subject results obtained from the high-resolution fMRI analysis (all data resampled at 1 mm isotropic and smoothed with a 2 mm FWHM Gaussian kernel). The DMN overlaid to the single subject T₁ data is presented in three selected slices (sagittal, coronal and transversal) for the 1 mm (top row), 1.5 mm (center row) and 2 mm (bottom row) data.

Figure 6. Single subject GLM back projection of individually selected DMN ICs at 1.5 mm

a) T-map (FDR corrected q = 0.05) (zoomed in sagittal and transversal) super imposed inverted T₂* (top) anatomical data. Note the regions of inverted phase (blue color, highlighted by arrows) coinciding with hyper-intense regions in the inverted T₂* images (bottom). b) Single subject time course (last 120 TRs) of selected regions of in phase (red) and inverted phase (blue) with respect to the DMN modulations.

Figure 7. Group (fixed effects) GLM back projection of individually selected DMN ICs at the different resolutions overlaid to mean anatomical data

a) Group t-maps (zoomed in sagittal and transversal) showing the full distribution of t-values in the pre-cuneus and parietal regions of the DMN. Note the higher SNR available in the 2 mm acquisitions (bottom row) and the regions of inverted phase (blue color, highlighted by arrows) visible in the 1 mm (top row) and 1.5 mm (center row) data.

Figure 8. Functional to anatomical correspondence analysis conducted within the pre-cuneus region for voxels significantly activated (group GLM back projection; p = 0.05 uncorrected) by DMN modulations

a) Histograms representing the absolute count of voxels within the selected ROI (gray line) and the active voxels for the 2 mm (green line), 1.5 mm (blue line) and 1 mm (red line) data. The histograms are reported with respect to the mean grayscale value indicating the approximate tissue segregation (low values = gray matter; high values = white matter). b) Normalized histograms, with respect to the total number of voxels, representing the absolute count of voxels within the selected ROI (gray line) and the active voxels for the 2 mm (green line), 1.5 mm (blue line) and 1 mm (red line) data. The histograms are reported with respect to the mean grayscale value indicating the approximate tissue segregation. c) Ratio of the 2 mm and 1 mm normalized histograms (red line) and of the 2 mm and 1.5 mm normalized histograms (blue line).

Figure 9

Group results (p = 0.05) obtained from the high-resolution fMRI analysis (all data resampled at 1 mm isotropic and smoothed with a 2 mm FWHM Gaussian kernel). The mean DMN, obtained averaging individually selected ICs in Talairach space, is overlaid to the mean T₁ data. Three selected slices (sagittal, coronal and transversal) are presented for the 1 mm (top row), 1.5 mm (center row) and 2 mm (bottom row) data.

Figure 10. Group results (p = 0.05) obtained from the high-resolution fMRI analysis (all data resampled at 1 mm isotropic and smoothed with a 2 mm FWHM Gaussian kernel)

a) The mean visual resting state component, obtained averaging individually selected ICs in Talairach space, is overlaid to the mean T₁ data. One selected transversal slice is presented for the 1 mm (left), 1.5 mm (center) and 2 mm (right) data. b) The mean somato-sensory component, obtained averaging individually selected ICs in Talairach space, is overlaid to the mean T₁ data. One selected transversal slice is presented for the 1 mm (left), 1.5 mm (center) and 2 mm (right) data. c) The mean somato-sensory component, obtained averaging individually selected ICs in Talairach space and overlaid to the mean cortical and partially inflated representation of the left hemisphere of the four subjects, is presented for the 1 mm (left), 1.5 mm (center) and 2 mm (right) data.