Synopsis
Combination of
diffusion weighted MRI with orthogonal measures such as T$$$_2$$$-weighting has
been proposed to overcome the fit degeneracy found in microstructure modeling
of diffusion signals. However, the repetition of diffusion measurements at
different TE leads to unacceptably long acquisition times, hindering clinical
applicability of this approach. Here, we propose an accelerated acquisition using
a multi spin echo diffusion and T$$$_2$$$-weighted sequence which samples each
diffusion weighting at several TEs with a CPMG read-out train after the
standard monopolar diffusion encoding spin echo. In the current configuration
this speeds the acquisition up by a factor of 2.5x.
Purpose
Microstructural
modeling of diffusion weighted MRI aims to quantify mesoscopic features probing
the white matter integrity [1-4]. These features might serve as sensitive and
specific biomarkers of microstructural changes associated with brain
development, aging and pathology. Recent work shows however that even fairly
simple multi-compartment diffusion models do not provide unique plausible solutions
[5]. A potential remedy is the addition of orthogonal information provided by a
range of diffusion times [6], advanced $$$b$$$-tensor encoding [7] or the
addition of T$$$_1$$$, T$$$_2^*$$$ or T$$$_2$$$ weightings [8-14]. To combine
diffusion and T$$$_2$$$ relaxometry [8], diffusion acquisitions need to be
repeated at different echo times (TE) thus necessitating an unacceptably slow
measurement. Here, we propose an
accelerated fused T$$$_2$$$-relaxometry-diffusometry acquisition. In our
approach we acquire for each diffusion weighting multiple full 2D EPI $$$k$$$-spaces
for each of several TE in a multi spin echo sequence (Fig 1). This translates
to a 2.5x reduction in scan time. In this work we demonstrate the feasibility
of accelerating T$$$_2$$$-relaxometry-diffusometry by using a multi spin echo
sequence in vivo in a clinical 3T
scanner.
Methods
Sequence: In the proposed custom-made multi spin echo
EPI diffusion sequence (Fig 1), the monopolar gradients in the initial 90°-180°
spin-echo block apply diffusion encoding and an initial spin echo image is
acquired with an EPI readout train. The subsequent 180° RF-pulses form a CPMG
spin echo train repeatedly refocusing the diffusion weighted signal at
increasing TE where subsequent identical EPI readouts are performed. All echoes
in the readout-train have similar diffusion weighting, but distinct TE. To
avoid unwanted ghost-echoes, a non-repeating set of crushers is added to all
180° pulses on all three gradient axes. Flip angle imperfections accumulate in
the CPMG train and add up to a non-negligible reduction in signal amplitude.
This effect is corrected by isolating the impact of each 180° RF pulse from the
non-diffusion-weighted $$$b_0$$$-image and a set of $$$b_0$$$-correction images
with carefully chosen echo time combinations. All gradients, both diffusion and
imaging, are included in the calculation of the $$$b$$$-matrices. The MSE-EPI
pulse sequence proposed here would be the first to integrate full k-space
single shot EPI with a combined diffusion and T$$$_2$$$-weighting.Data: Diffusion-relaxometry datasets were collected
using a product spin echo (SE-EPI) and the proposed custom-made multi spin echo
(MSE-EPI, Fig 1) diffusion sequence. In both sequences, 30 isotropically
distributed directions were acquired for each of $$$b\,=\,500,1000,2000,3000$$$
and $$$4000\,\mathrm{s/mm^2}$$$ and TE$$$\,=\,71, 107, 143$$$ and $$$179\,\mathrm{ms}$$$.
Due to scanner limitations, the $$$b\,=\,4000\,\mathrm{s/mm^2}$$$ could not be
acquired for the shortest TE with the SE-EPI sequence. Datasets were acquired
of a healthy volunteer (female, 24y/o) on a 3T clinical
scanner (MAGNETOM Prisma, Siemens, Erlangen) using a 20-channel head coil (TR$$$\,=\,4000\,\mathrm{ms}$$$, 2.5$$$\,\mathrm{mm}$$$
isotropic resolution, FoV$$$\,=\,210\,\mathrm{mm}$$$, 36 slices, multiband
acceleration of 2, GRAPPA 2, PF 6/8) in a single scan session (SE-EPI: 32:49$$$\,\mathrm{min}$$$,
MSE-EPI: 13:02$$$\,\mathrm{min}$$$). Images were denoised [15], intensity corrected (N4), corrected
for susceptibility, eddy currents and subject motion using $$$\mathrm{eddy}$$$ [16] and registered to the first
diffusion image using $$$\mathrm{flirt}$$$ [16].
Tissue segmentation (MRtrix3, $$$\mathrm{5ttgen}\,{fsl}$$$)
was performed on an MPRAGE image (1mm isotropic resolution, TR/TE$$$\,=\,2300/2.87\,\mathrm{ms}$$$).
A single T$$$_2$$$-DKI-compartment was fitted to the data using an
unconstrained linear least square estimator in Matlab (Mathworks). Note that
the diffusion time is constant for the different TE with the MSE-EPI, whilst it
increases with TE for the SE-EPI.Results and Discussion
Fig. 2 compares raw
diffusion and T$$$_2$$$-weighted images of the SE and MSE-EPI sequences. Image
contrast is the same, though SNR is lower in the high TE, high $$$b$$$-value
images of the MSE-EPI sequence as can be expected. Similarly, parameter maps
(Fig. 3) are comparable with the exception of a minor slice misalignment. ADC-values
of the MSE-EPI sequence are higher due to the lower (constant) diffusion time
relative to the SE-EPI where the diffusion time increases with TE. Some
differences in the Mean Kurtosis map (Fig. 3, MK) are caused by an
ill-conditioned DKI-fit due to lower SNR in high $$$b$$$-value, high TE MSE-EPI
images. Good agreement of both acquisitions is evident in a voxel-by-voxel
direct comparison of the DKI and T$$$_2$$$-parameters (Fig. 4). Scatterplots of
these DKI and T$$$_2$$$-parameters illustrate the value of T$$$_2$$$-relaxometry
as an orthogonal measure in combination with a diffusion acquisition.Conclusion
With a multi spin
echo sequence the combination of diffusion and T$$$_2$$$-weighted measurements
can be fused in a single readout train, thus accelerating the acquisition with
a factor 2.5. This shortened acquisition time increases the feasibility of orthogonal
diffusion-T$$$_2$$$ acquisitions in research and clinical applications.Acknowledgements
This
project is supported in part by PHS grants R01-CA111996, R01-NS082436 and
R01-MH00380.References
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