Khader M Hasan^{1}, Refaat E Gabr^{1}, John A Lincoln^{2}, and Ponnada A Narayana^{1}

We describe a comprehensive multishell and multifaceted icosahedral diffusion MRI protocol that enables whole brain coverage in less than 10 minutes using multiband (MB) technology at 3 T. We show the protocol utility in providing estimates of blood fraction, extent of CSF-contamination, diffusion tensor and kurtosis derived measures including fractional, axonal water fraction and extracellular tortuosity. The diffusion gradient encoding is based the Icosa6 and Icosa15 sets forming the Icosa21 for additional quality assurance. In this report we describe the protocol, show feasibility and utility for mapping a host of useful quantitative measures in the same session without repeated scans.

Diffusion-weighted MRI has advanced knowledge of the
organization and functioning of the central nervous system in both health
and disease. Three clinically-used dMRI quantitative models including
intravoxel incoherent motion, IVIM^{1}, diffusion tensor, DT^{2}, and diffusion
kurtosis, DK^{3} have been explored at low, medium and high b-values,
respectively. IVIM measurements (b<300 s.mm^{-2}) provide information
about micro capillary blood volume fraction, DTI using b<1200 s.mm^{-2 }provides
scalar and orientation maps while DKI
provides clues about restricted diffusion utilizing a minimum of two shells b>=1000 and b<3000 s.mm^{-2}. Due
to time considerations for clinically feasible scans, these models have not been consolidated. DTI uses a single shell (b~1000 s.mm^{-2}), DKI uses two shells, and both require a reference or b=0 map to decouple
the water content and relaxation effects from attenuation by random
translational diffusion. The b=0 map contains contributions from the blood
fraction, cerebrospinal fluid (CSF) and free water in the voxel may also
contaminate the signal which affect the accuracy of the sought maps^{4}. Utilizing
a reference-less dMRI with b>300 s.mm^{-2} minimizes blood and reduces
CSF contamination as an alternative to fluid-attenuation by inversion recovery^{5}.

Whole brain data were collected
on two healthy adults using a Philips Ingenia 3T system and a 32-Channel RF coil with multiband technology. dMRI protocol utilized a single-shot
echo-planar sequence with a SENSE factor=2 and MB=2 for acquiring data with b=0, three shells using diffusion gradient pulses along the orthogonal
X/Y/Z orientations and Icosa6 at b=50, 100, 200 s mm^{-2}, respectively. Three
additional shells with Icosa21 at b=400, 1200, 2200 s mm^{-2}, isotropic
voxel size 2mm, TR/TE=6000/90 ms; see **Figs. 1, 2**). Pseudo-continuous arterial spin labeling (pCASL), multi spin-echo T2w, and high spatial resolution
multi gradient-echo susceptibility-weighted data were also collected to
estimate cerebral blood flow, iron-rich gray matter, and vessels while also
collecting phase maps*. **Data
Processing*: The averaged b=0 volume was used for motion and distortion
corrections. DWI data were processed in multi-passes using the encoding b-matrix
formalism for both DTI ^{2, 8-10 }and DKI as detailed elsewhere ^{3,11,12 }with b=0 and b>=400 to obtain asymptotic estimates for the single tensor and blood fractions^{1} and
subsequently fit using linear and non-linear mixed Gaussian multi-exponential models. DKI was
implemented using b=400, 1200, and 2200 shells with and without utilizing the
b=0 map. The data were also run through windows-based freely available
dMRI packages that use DTI (DTIstudio) or beyond (NODDI, DK-Estimator, Trackvis, ExploreDTI, DSIStudio; see tabulation and web links^{13}).

**Figure 1 **shows the data quality represented
by one axial section and the signal profiles (means and standard deviations vs. order) in white matter (genu of corpus callosum) and CSF at the right anterior horn of lateral ventricle. The protocol design is illustrated in **Figure 2 **where the signal profile is shown in the right thalamic
gray matter. **Figure 3** shows the IVIM
fraction, DT radial diffusivity, principal eigenvector, fractional anisotropy, mean & radial kurtosis,
extracellular tortuosity, and axonal water fraction (AWF). The CBF map, R2*, water content,
and a 3D volume render of the motor cortices and projection
motor pathway traced and visualized using the dMRI data (http://dsi-studio.labsolver.org/). **Figure 4.a** fuses R2* map highlighting veins with the DTI-derived |FA*pvec|. Note the extent of vessel contamination on the posterior corpus callosum.** Figure 4.b** fuses R2* with FA derived w/o b0 keeping the b=400,1200@Icosa21. An increase in FA is shown in green and is best seen in regions surrounded by CSF (i.e. fornix). This interesting effect has been described in past DTI literature utilizing FLAIR or CSF/free water modeling.^{14,15}

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