Synopsis

Initial phantom and in vivo results of a multi-echo Stejskal-Tanner EPI sequence are presented demonstrating the feasibility of rapid measurements for diffusion tensor and T₂ correlations. The diffusion and T₂ maps are artefact-free and are found to be very similar to the ones derived from the conventional individual-echo methods. However, the data tend to display slightly overestimated diffusivities and T₂, which need to be investigated further.

Compared to the standard method, the proposed multi-echo sequence reduces the scan time by a factor of five, which is necessary to make multidimensional diffusion techniques feasible in clinical settings.

Introduction

Multidimensional MRI methods have recently been used in a variety of in vivo investigations, offering a non-invasive characterisation of tissue heterogeneity with an unprecedented level of detail. In particular, it has been demonstrated that simultaneously measuring diffusion and transverse relaxation (D-T₂) properties can provide valuable information on the underlying microstructure¹. Moreover, it has been shown that this kind of analysis leads to a more accurate, precise and robust estimation of the model parameters², such as in case of the free water elimination (FWE) method³. However, measuring D-T₂ properties simultaneously requires long scan times.

In this work, we propose a multi-echo Stejskal-Tanner EPI sequence to acquire D-T₂ data more efficiently, drastically reducing the scan time. A complete five-echo D-T₂ protocol was acquired in ~7min and the performance was compared to the standard single-echo procedure acquired in ~35min.

Methods

A multi-echo Stejskal-Tanner sequence acquiring five spin-echo (SE) EPI readouts per repetition time (Fig. 1) was implemented on a 3T PRISMA scanner (Siemens Healthineers, Germany). The sequence was compared to the conventional approach of acquiring each echo individually (“individual-echo” approach).

The sequence was first tested on a diffusion fibre phantom composed of five parallel-fibre tubes⁴, doped with different concentrations of MgCl₂$$$\cdot$$$6H₂O: 0, 1.35, 2.30, 3.01, 3.55mol/l. In vivo measurements were performed on a healthy male 34-year-old volunteer from whom written informed consent was obtained in line with legal requirements prior to the measurements.

The sequence parameters for the phantom experiments were: TE = 66, 166, 266, 366 and 466ms; diffusion gradient duration and separation, δ=14ms and Δ=36ms; b-values(directions) = 0(8), 0.625(12) and 1.25(26)ms/μm²; matrix-size=128⨉128⨉8; voxel-size=2³mm³.

For the in vivo experiments: TE=58, 86, 114, 142 and 170ms; δ=14ms and Δ=31ms; b-values(directions) = 0(8), 0.4(12) and 0.8(26)ms/μm²; matrix-size=96⨉96⨉40; voxel-size=2.5³mm³.

Additionally, a conventional single-echo spin-echo sequence to obtain reference T₂ values was employed. Echo-times for the phantom were: TE=12, 62, 112, 212, 312, 412 and 512ms. For the in vivo experiments: TE=12, 32, 52, 82 and 122ms. The repetition-time in all experiments was TR=9s.

Individual- and multi-echo data were processed using the method assuming anisotropic, Gaussian diffusion (DTI) and monoexponential transverse relaxation (DTIT₂), in which the signal, S, is expressed as:

$$S(\mathrm{TE},b,\mathbf{n})=S_0e^{-\frac{\mathrm{TE}}{\mathrm{T_2}}e^{-b\mathbf{n}^\mathrm{T}\mathbf{D}\mathbf{n}}}~~~~~~~~(1)$$

where S₀, T₂ and D are the proton density, the transverse relaxation time and diffusion tensor, respectively; b and n are the diffusion weighting strength and direction.

Model parameters, $$$\boldsymbol{\hat{\theta}}=[\ln(S_0),\mathrm{D}_{11},\mathrm{D}_{12},…,\mathrm{D}_{33},1/\mathrm{T_2} ]^\mathrm{T}$$$, were estimated by fitting Eq. 1 to the experimental datasets, using the weighted-linear least-squares method:

$$\boldsymbol{\hat{\theta}}=(\mathbf{X}^\mathrm{T}\mathbf{wX})^{-1}\mathbf{X}^\mathrm{T}\mathbf{wy}~~~~~~~~(2)$$

where y is a column vector whose elements are given by y_i=ln(S_i) and the weighting matrix, w, is a diagonal matrix whose elements are given by w_i,i=S_i² (i=1...N, the number of measurements). The i^th row of the design matrix, X, is written as $$$X_{i,:}=[1,-b_in^2_{ix},-2b_in_{ix}n_{iy},…,-b_{iz}n^2_{iz},-\mathrm{TE}_i]$$$. DTI-based metrics, axial, radial and mean diffusivities (AD, RD and MD) and fractional anisotropy (FA), were evaluated⁵.

Results

Fig. 2 shows AD, RD and T₂ maps for the individual-echo and the multi-echo approaches. The maps acquired using multi-echo acquisition are in agreement with those with individual-echo acquisition. Small differences are visible in T₂ between 3 and 5 echoes in the multi-echo case.

Fig. 3 shows a comparison of the mean AD, RD and T₂ in six regions of interest (ROIs), five in the tubes and one in the bulk.

In vivo FA, MD and T₂ maps shown in Fig. 4 demonstrate that the multi-echo approach provides comparable results.

Fig. 5 shows the histograms of FA, MD and T₂ for the whole FOV, each compared to the reference and the individual-echo method. In the multi-echo case, FA is shifted towards lower values, whereas MD and T₂ become shifted towards larger values, in line with the phantom results (Figs. 2-3).

Discussion

The results demonstrate that the proposed sequence produces reasonable results while reducing the scan time. However, it tends to slightly overestimate T₂ and diffusivity, which needs to be further investigated. In the phantom case, the fitting instability of bulk T₂ values is due to its extremely long values (>2.5s), which are not present in vivo.

In the current implementation in vivo, only 3 echoes are usable as echo 4 and 5 show low SNR values and are affected by several artefacts, probably due to the accumulation of imperfect RF refocusing effects. Other phase cycling approaches, as well as the use of parallel-excitation methods could be used to improve the RF refocusing.

Conclusions

Acknowledgements

References

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