3D distortion-free diffusion imaging using an accelerated multi-shot diffusion-prepared sequence
Elisa Roccia1, Radhouene Neji1,2, Vicky Goh3, and Isabel Dregely1

1Biomedical Engineering, King's College London, London, United Kingdom, 2Siemens Healthcare, Frimley, United Kingdom, 3Cancer Imaging, King's College London, London, United Kingdom


Current methods for cancer diffusion imaging employ 2D single-shot diffusion weighted echo planar imaging sequences, which are fast but have limited resolution and are prone to distortion artefacts. The purpose of this work is to achieve 3D high-resolution and distortion-free diffusion imaging suitable for cancer precision diagnostics and therapy planning. A multi-shot diffusion-prepared sequence with gradient echo readout, centric encoding, and accelerated variable density acquisition was developed and tested in healthy volunteer brains as an exemplar. A full set of 2.2-fold accelerated diffusion weighted images in three diffusion directions was acquired in 4:30 min producing quantitative 3D distortion-free ADC maps.


Diffusion-weighted MRI imaging (DWI) is a key component of multi-parametric MRI protocols in cancer imaging for its ability to probe tissue microstructure. Current clinical DWI protocols are based on 2D diffusion-weighted single-shot echo planar imaging (SS-DW-EPI), which is fast, but particularly prone to geometric distortion and of limited spatial resolution. This limits diagnostic accuracy and prohibits its use in emerging MR-guided personalized treatment options, including radiotherapy planning with its high requirement for 3D geometric accuracy.

Multi-shot (MS) sequences can achieve high resolution and have been successfully used for diffusion-weighted imaging of the brain 1,2 (“readout-segmented” EPI, RESOLVE).

MS sequences can be combined with diffusion-preparation (DP) modules (as opposed to diffusion-weighted) 3. DP sequences have the advantage that diffusion-encoding and readout are separated and thus can be optimized independently. Disadvantages include the longer acquisition time.

The purpose of this study is to implement a 3D MS-DP sequence with gradient echo readout (3D DP-MS-GRE) to achieve high-resolution, distortion-free, 3D diffusion using the brain as exemplar.


Diffusion sequence. A prototype 3D MS-DP-GRE sequence was implemented. Diffusion preparation is achieved with a twice-refocused spin-echo (TRSE 4) module with a pair of adiabatic refocusing pulses and two pairs of gradients, placed at the beginning of each shot (Figure 1). Data were acquired with a 3D Cartesian k-space trajectory with centric profile order (VD-RAD 5, CASPR 6), both fully sampled (FS) and two-fold (x2.2) prospectively accelerated using a variable density (VD) sampling (Figure 1). Undersampled images were reconstructed in MATLAB using iterative and regularized TV-SENSE reconstruction 7,8.

Experiments. Data were acquired for four healthy subjects on a 3T PET-MR scanner (Biograph mMR, Siemens Healthcare, Erlangen, Germany), following approval by the local institutional review board and informed consent. MR measurements were obtained using 3D MS-DP-GRE with the following acquisition parameters: number of GRE RF pulses per shot = 96, transversal orientation, FA=12o, GRE-TE=4.7ms, FOV=240x240mm2, resolution 1.5x1.5x5mm3, DP-TE=90ms, b-value (diffusion weighting) = 50,800,1200s/mm2, acquisition time (AT) per image=1:06/0:30min (FS/VD), total AT=9:54/4:30min (three diffusion directions for each b-value). To demonstrate the potential of multi-shot diffusion imaging, a higher resolution (1x1x3mm3) MS-DP-GRE dataset was also acquired (total AT=14:34min, FS). As a reference standard to evaluate apparent diffusion coefficient (ADC) quantification, a clinical standard 2D SS-DW-EPI was acquired in transversal orientation, acquired resolution 3x3mm2 (interpolated 1.57x1.57mm2), 5mm slice thickness, b-value = 50, 800, 1500 s/mm2 (2, 5, 15 averages each), total AT=6:45 min. As a reference standard to evaluate geometric distortion, a clinical standard high-resolution 2D T2w TSE was also acquired.

Data analysis. ADC maps were obtained from the trace diffusion images using a standard mono-exponential fitting routine. To compare ADC estimates mean and standard deviation of ADC were measured in manually drawn regions of interest (ROIs) in white matter (WM) and grey matter (GM).


Diffusion images. Trace b-value images obtained with the proposed 3D MS-DP-GRE sequence and corresponding ADC map are shown in Figure 2(A), together with the clinical standard 2D SS-DW-EPI ADC map, for two representative healthy subjects. The MS-DP-GRE-derived ADC values were 0.65±0.07 and 0.97±0.09 μm2/ms for WM and GM respectively (Figure 2(B)), and showed good contrast between WM and GM.

High resolution. ADC maps obtained with the proposed 3D MS-DP-GRE in low and high resolution are shown in Figure 3(A). Reformats in transversal, sagittal and coronal planes of the high-resolution 3D acquisition are shown Figure 3(B).

Acceleration. The accelerated acquisition enabled a scan time reduction of 55%. The TV-SENSE reconstructed images showed comparable image quality to the FS, and no statistically significant difference in ADC estimates was observed (Figure 4).

Geometric distortion. With the proposed 3D MS-DP-GRE geometric distortion was substantially reduced compared to the standard 2D SS-DW-EPI using the anatomical 2D T2w-TSE as reference (Figure 5).

Discussion and Conclusion

The experiments performed in this work show that an accelerated 3D MS-DP-GRE approach can achieve 3D diffusion mapping with ADC quantification in agreement with literature values 9,10 and with substantially reduced distortion in a total acquisition time of 4:30min. This should prove useful for MR-guided focal therapy and interventions, including MR-guided radiotherapy planning. Future work will address the motion sensitivity of the multi-shot approach, i.e. image corruption due to inter-shot motion and phase incoherence, to enable robust ADC quantification also in motion-affected organs.


This work was supported by the King’s College London & Imperial College London EPSRC Centre for Doctoral Training in Medical Imaging [EP/L015226/1]; the Wellcome EPSRC Centre for Medical Engineering at Kings College London [WT 203148/Z/16/Z]; the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London; the King’s Health Partners Research and Development Challenge Fund; TOHETI; NIHR BRC; GSTT/KCL BRC; CRUK/EPSRC Cancer Centre; Siemens Healthineers. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.


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Figure 1: Sequence diagram of the proposed multi shot diffusion sequence. Each shot consists of a diffusion preparation module (DP) with a pair of adiabatic refocusing pulses and two pairs of gradients (duration DP-TE = 90 ms), a GRE readout, and a break for magnetization recovery. Each GRE readout acquired 96 segments (ky-kz samples) arranged as a Cartesian spiral in ky-kz space. RF: radiofrequency pulse; Gdiff: diffusion gradients.

Figure 2: (A) Trace b-value images (b-value = 50, 800, 1200 s/mm2) obtained with the proposed 3D MS-DP-GRE sequence, corresponding 3D MS-DP-GRE ADC map, and clinical standard 2D SS-DW-EPI ADC map for two representative subjects. (B) ADC values estimated in white matter (WM) and grey matter (GM) ROIs drawn in the ADC maps in (A) showed good contrast with the proposed 3D MS-DP-GRE. FS: fully sampled.

Figure 3: Comparison of ADC maps obtained with the standard low resolution 2D SS-DW-EPI and proposed 3D MS-DP-GRE with low and high resolution (1x1x3 mm3). (B) Reformats of the high resolution ADC map in sagittal and coronal planes.

Figure 4: (A) High b-value images (b-value = 800 s/mm2) from the fully sampled acquisition (FS) and the accelerated one (VD), reconstructed with TV-SENSE. The total acquisition time (AT) refers to the full set of three b-value images and three diffusion directions. (B) Comparison of the ADC values estimated with the two approaches (FS and VD). n.s.: non statistically significant difference.

Figure 5: Geometric distortion of standard 2D SS-DW-EPI and proposed 3D MS-DP-GRE (diffusion-weighted images with maximum b-value) compared to the anatomical 2D T2w-TSE for a representative slice of a healthy subject’s brain dataset. It is possible to observe the geometric distortion in the frontal lobe of the brain occurring in the SS-DW-EPI image, whereas the proposed MS-DP-GRE is distortion-free.

Proc. Intl. Soc. Mag. Reson. Med. 27 (2019)