Highly accelerated fat-fraction measurements for clinical trials in muscular dystrophy
Thomas Loughran1, David M Higgins2, Anna Coombs1, Michelle McCallum3, Volker Straub3, and Kieren Grant Hollingsworth1

1Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom, 2Philips Healthcare, Guildford, United Kingdom, 3Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom

Synopsis

Fat fraction measurement in muscular dystrophy is important for therapy trials. Accelerated acquisition reconstructed by combined compressed sensing and parallel imaging (CS-PI) can improve patient compliance. Eight patients with Becker muscular dystrophy were recruited and prospectively undersampled data at ratios of 3.65×, 4.94×, and 6.42× were acquired in addition to fully sampled data. The CS-PI reconstructions were of sufficient quality at 3.65× and 4.94× acceleration. Compared to fully sampled data, non-significant bias and 95% limits of agreement of 1.65%, 1.95% and 2.22% were found for the three CS-PI reconstructions, significantly outperforming conventional parallel imaging alone.

Introduction

Chemical shift fat fraction measurement in muscular dystrophy provides an objective non-invasive method of assessing the efficacy of gene therapy trials, independent of patient motivation1. Duchenne muscular dystrophy is a devastating genetic disease which manifests in boys from the age of 3-5 and progressively destroys skeletal, cardiac and respiratory muscles. It causes the replacement of muscle by fat and fibrosis, and is now the subject of first-in-human therapy trials. The varying motivation of the boys makes traditional physical function tests too variable for sensitive clinical trial evaluation, so objective MRI measures of muscle involvement have become important. However, the boys have limited tolerance for keeping still in the scanner and the cost of lengthy MR acquisitions limits their use. In this study, we validate highly accelerated fat fraction measurements using data undersampling and combined compressed sensing and parallel imaging (CS-PI) reconstruction in adults with the similar, but slower progressing disease, Becker muscular dystrophy. We looked in particular at the optimization of reconstruction parameters across an adult cohort, the image quality of accelerated images and the fidelity of the muscle fat fractions.

Methods

Fully-sampled and undersampled data were acquired on a 3T Philips Achieva and a 6 channel cardiac coil using a custom 3D gradient echo with variable density Poisson disk undersampling at 3.65´, 4.94´ and 6.42´ accelerations 2. A 256´190´48 matrix (1.25´1.0´5mm) was used with TR/TE/FA = 10ms/4.40,5.18,5.96ms/3o. The acquisition times were 273s (full) and 75s, 55s and 43s (undersampled). 8 patients with Becker muscular dystrophy were recruited under local ethical approval and informed consent. Imaging blocks were acquired for calf and thigh muscles. Undersampled data were reconstructed with CS-PI using an L1-ESPIRiT approach 3, optimizing the reconstruction parameters as previously described 4. A coherent 3.36x undersampling was acquired for GRAPPA (PI) reconstruction alone. Fat fraction maps were calculated with a 6-component fat model and single component R2* modelling 5. Regions of interest were drawn on 10 axial sections on the fully sampled left leg for 12 anatomical areas (Table 1). The mean fat fraction was calculated for each anatomical area on the fully and undersampled reconstructions. 940 pairs of data were successfully evaluated to derive Bland-Altman parameters of bias and 95% limits of agreement. To assess image quality, two independent observers evaluated the percentage of anatomical ROIs that could be successfully delineated on each accelerated reconstruction.

Results and Discussion

Figure 1 shows that excellent image quality was obtained with CS-PI reconstruction. The optimal reconstruction parameters were found to be consistent between acceleration factors and across the patient cohort 3, providing confidence to use the accelerated protocol prospectively without fully sampled data. Table 1 shows the fat fractions were faithfully reproduced in the accelerated scans and the Bland-Altman analysis of fat fractions (Table 2, left) showed no net bias and demonstrated that CS-PI reconstruction outperforms PI alone. The two observers were able to confidently identify all ROIs in the 3.65x and 4.94x CS-PI images, but not in the 6.42x CS-PI image, where subtle features were absent, or the 3.36x PI only image (Table 2, right).

Conclusion

We have: (1) prospectively validated a reduction of scan time by a factor of up to 5x with excellent image quality and accurate fat fraction, which will reduce scan cost and increase patient compliance with fat fraction measurements; (2) demonstrated that combined CS-PI is substantially better than PI alone.

Acknowledgements

Medical Research Council New Investigator Research Grant to KGH (G1100160).

References

[1] Willis PLoS ONE 2013;8:e70993, [2] Loughran Radiology 2015;275:570, [3] Uecker MRM 2014;71:990, [4] Hollingsworth MRM 2014;72:1610, [5] Tsao Magn. Res. Med. 2013;70:155

Figures

Figure 1 : Fat fraction maps for a thigh (left) and a calf (right) of BMD patients, fully sampled and accelerated with CS-PI reconstructions

Table 1: Mean fat fractions for 8 patients on a per ROI basis (%)

Table 2 : Bland-Altman analysis of the undersampled vs fully sampled fat fractions for 940 ROIs (left) and the % of ROIs successfully resolved by 2 independent observers



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
4218