Fiber orientation distributions (FODs) of white matter (WM) are commonly estimated from brain diffusion MRI data with spherical deconvolution (SD) approaches. Typically, only WM is considered to be anisotropic in SD, relying on suboptimal isotropic modeling of grey matter (GM). Here we present a general framework to reconstruct multiple anisotropic FODs (mFODs) from multiple response functions, allowing for the investigation of anisotropy in GM. The estimated mFODs were evaluated on a dataset from the HCP project with five response functions generated with the diffusion kurtosis and NODDI approaches, and their performances compared to state-of-the-art SD approaches.
SD was reformulated to account for n response functions, leading to the multiple FOD (mFODs) SD approach. The problem can be formally written as: $$$\sum_{i=1}^{n}{f_{i}K_{i}}$$$, where S is the MS dMRI signal, and fi is the signal fraction associated to each FOD. The approach was implemented within the modified Richardson-Lucy iterative scheme3,4.
For proof of concept, we considered 5 different response functions K. K1 described highly oriented fibers, and was generated with the DKI model using tensor and isotropic kurtosis values derived from the data within a WM mask. K2, K3 and K4 described three configurations of dispersed fibers generated with the NODDI model5 using default values but with an orientation dispersion value of 1.5 and with intra-cellular fractions of 0.9, 0.6 and 0.3, respectively. K5 was generated using the ADC model and with a diffusion value 3x10-3mm2/s to account for free water diffusion.
Data of a subject from the Human Connectome Project (HCP)6, acquired with resolution 1.25mm isotropic, 18 volumes at b=0s/mm2, 90 volumes at b=1000,2000,3000s/mm2 were fit with mFODs SD, resulting in 5 fractional maps and 4 anisotropic FODs. The fractional maps were compared to the anatomical segmentation obtained from the T1 data7.
Fiber tracking of each mFOD separately was performed in ExploreDTI8 using a 1.25mm seed resolution, 0.6mm step size and 45 degrees angle threshold. Tract density maps were computed for each tracking result and compared with results obtained with constrained SD (CSD) and MS-CSD. Subsequently, tracking was performed considering two strategies to track from the multiple FODs simultaneously: 1) considering their sum weighted by their corresponding signal fraction (mFODs-LI) and 2) choosing voxel-wise the FOD corresponding to the greatest signal fraction (mFODs-MAX). Tracks not traversing GM were discarded.
Figure 1 shows the signal fractions obtained with mFODs SD. These fractions have an excellent spatial agreement with the fractions of WM, GM and CSF derived from the structural image. The mFOD1 and mFOD2 magnitudes were mostly non-zero in WM areas, whereas non-zero values in mFOD3 and mFOD4 mainly covered the cortical areas and subcortical GM, as shown in Figure 2. Further, the orientations of mFOD3 and mFOD4 were mostly perpendicular to the GM folding. Similar results were observed from the tracking of the individual FODs and their density maps, shown in Figure 3. The tracking of mFOD1 and mFOD2 covered large parts of the WM, whereas the tractograms of mFOD3 and mFOD4 contained many short connections (U-fibers) and large part of the cerebellar structure.
Figure 4 compares the FODs obtained with CSD, MS-CSD, mFOD-s-LI and mFODs-MAX on an axial slice. MS-CSD effectively suppressed CSF contamination, but both MS-CSD and CSD were characterized by a large number of spurious peaks in the GM. Conversely, both mFODs-LI and mFODs-MAX provided a cleaner characterization of GM FODs. The whole brain tracking obtained with CSD, MS-CSD and mFODs-MAX are shown in Figure 5. The tractogram provided by mFODs-MAX showed better description of the cerebellar structure and cleaner depiction of the cortical gyri, as shown by the tissue type encoded tractograms. Further, the transition of tracts from WM to GM appear to be better characterized with the mFODs-MAX approach.
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