Standardisation and quantification of 23Na-MRI: repeatability and reproducibility of sodium imaging across two independent sites
Damien J. McHugh1,2, Frank Riemer2,3, Hamied A. Haroon1, Geoff J.M. Parker1,2,4, and Ferdia A. Gallagher2,3

1Centre for Imaging Sciences, The University of Manchester, Manchester, United Kingdom, 2CRUK & EPSRC Cancer Imaging Centre in Cambridge & Manchester, United Kingdom, 3Department of Radiology, University of Cambridge, Cambridge, United Kingdom, 4Bioxydyn Ltd., Manchester, United Kingdom


This work investigates the repeatability and reproducibility of total sodium concentration (TSC) estimates in the human brain. Healthy volunteers were scanned twice at two different sites using comparable 3D Cones acquisitions, and region of interest TSC values were compared. Consistent TSC estimates were observed across repeated scans at different sites, and, for robust multi-site comparisons, a need was identified for standardisation of non-Cartesian data reconstruction. These preliminary results provide an initial step in the technical validation of sodium MRI-derived cancer biomarkers.


Sodium MRI has the potential to probe the tumour microenvironment and provide quantitative biomarkers of treatment response in tumours, based on its sensitivity to cell viability and tissue microstructure1,2. For example, total sodium concentration (TSC) has been shown to be elevated in many tumours1,3, and is sensitive to chemotherapy in preclinical experiments4. If TSC is to have clinical utility as a biomarker in oncology, values should be repeatable within a given subject and comparable across different scanners and sites. This work presents preliminary results on the repeatability and reproducibility of TSC values in healthy volunteers, providing an initial step in the technical validation of sodium MRI-derived biomarkers5.


Sodium brain MRI was performed on two male volunteers (aged 35 and 27) scanned twice at two sites, A and B. One site used a GE 3 T MR750, and the other a Philips 3 T Achieva, and both used a 1H/23Na dual-tuned head coil (RAPID Biomedical GmbH, Rimpar, Germany). Scan-rescan repeatability was assessed after a short time outside of the scanner of between 20 and 80 minutes. Inter-site/inter-scanner reproducibility was assessed by performing the above protocol at sites A and B, up to 3 days apart. The scan protocol consisted of a 1H T1-weighted scan, followed by a 23Na 3D Cones6 acquisition: 4x4x4 mm3, 60x60x60 matrix, TR=100 ms, TE=0.5 ms, FA=90°, readout=10 ms, 3 averages, 11 minutes, Gmax=30 mT/m. 6552 (2184 x 3 averages) readouts were performed at each site, with an additional 3 dummy acquisitions at site A. 3D Cones images were reconstructed using k-space density compensation weights7,8 and the Image Reconstruction Toolbox9. Two effective matrix sizes, m = 250 and 350, were investigated for the weights calculation, both using an oversampling factor of 4. The same calibration phantoms (consisting of 4% agar, NaCl concentrations: 40, 80 mM) were used for all scans, and ROI mean signals in the phantoms were used to derive TSC maps, after applying a power image noise correction10. Manually-defined bilateral ROIs were drawn in cerebrospinal fluid (CSF), grey matter (GM), white matter (WM) and vitreous humour (VH), pooling all voxels for a given region. TSC repeatability was assessed using the coefficient of variation (CoV) of ROI median values for scans 1 and 2; mean repeatability across the 4 ROIs is reported for each subject at each site. Reproducibility was assessed using the CoV of ROI median values obtained for scan 1 at each site, again reporting mean values across the 4 ROIs.

Results and discussion

Figure 1 shows example images (subject 1), from each scan at the two sites, for reconstructions with m = 250 and 350. For a given m, images from site B were noticeably smoother than those from site A, a trend observed in both subjects. These results suggest that the weights calculation should be adjusted for each scanner, to prevent excessive smoothing. As images from site A using m=350 and from site B using m=250 were visually most similar, these datasets were used in the subsequent analysis. TSC maps are shown in Figure 2 (subject 2), and Figure 3 shows boxplots for each ROI in each subject, for both scans at both sites. General trends were consistent across all scans, with VH TSC higher than CSF, and similar values observed in GM and WM; mean±SD TSC for all scans were 92±11 mM (CSF), 24±6 mM (GM), 25±5 mM (WM) and 115±14 mM (VH). Precision may be improved by considering more ROIs or using GM/WM/CSF segmentation; note also that CSF and VH values are likely to be underestimated due to partial T1 recovery, and may suffer from pulsation and movement artefacts. Scan-rescan repeatability CoVs were consistently higher at site A than site B, 11% vs 2% (subject 1), and 7% vs 2% (subject 2), suggesting TSC measurements are more repeatable at site B than site A. It is likely that these findings are affected by differing levels of image artefact and the k-space weights used, with the generally smoother images from site B yielding higher repeatability. Inter-site/inter-scanner reproducibility CoVs for scan 1 were 4% and 9% for subjects 1 and 2, respectively.


Consistent TSC estimates were observed across repeated scans at different sites with different scanners. k-space weights are an important consideration when comparing multi-site non-Cartesian data; this will be investigated in future work, along with phantom and analytical point spread function analysis accounting for site-specific SNR. These developments will aid the standardisation of the reconstruction and analysis of sodium images acquired at different sites, in order to robustly evaluate image quality and quantification.


DJM and FR contributed equally to this work, and GJMP and FAG contributed equally to this work. This is a contribution from the Cancer Imaging Centre in Cambridge & Manchester, which is funded by the EPSRC and Cancer Research UK (C197/A16465 and C8742/A18097). This work was supported by the EPSRC (EP/M005909/1). This work was supported by a research agreement between Philips Healthcare and The University of Manchester. The authors acknowledge the contributions of Christian Stehning from Philips Research, Hamburg, Germany, Dave Higgins from Philips Healthcare, UK, and Rolf Schulte from GE Global Research, Munich, Germany.


1Ouwerkerk et al. Radiology. 2003;227:529-537. 2Thulborn et al. Neuroimaging Clin N Am. 2009;19:615-624. 3Ouwerkerk et al. Breast Cancer Res Treat. 2007;106:151-160. 4Schepkin et al. NMR Biomed. 2006;19:1035-1042. 5Imaging Biomarker Roadmap for Cancer Studies, Accessed November 8th, 2015. 6Gurney et al. Magn Reson Med. 2006;55:575-582. 7Riemer et al. MAGMA. 2014;27:35-46. 8Zwart et al. Magn Reson Med. 2012;67:701-710. 9Fessler and Sutton. IEEE Trans Signal Process. 2003;51:560-574. 10Miller and Joseph. Magn Reson Imaging. 1993;11:1051-1056.


Fig. 1. Reconstructed 23Na images for subject 1, from two scans at sites A and B, for reconstructions using weights calculated with effective matrix sizes of 250 (left) and 350 (right). Phantoms containing 40 mM and 80 mM NaCl are seen on either side of the images.

Fig. 2. TSC maps for subject 2, from two scans at sites A and B, using effective matrix sizes of 350 and 250, respectively.

Fig. 3. Boxplots of ROI TSC values from two scans at sites A and B, for subject 1 (left) and subject 2 (right).

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