Cerebral blood flow measurements correlate well in paediatric brain tumour patients using ASL- and DSC-MRI
Jan Novak1,2, Stephanie Withey1,2, Lesley MacPherson3, and Andrew Peet1,2

1Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, United Kingdom, 2Oncology, Birmingham Children's Hospital, Birmingham, United Kingdom, 3Radiology, Birmingham Children's Hospital, Birmingham, United Kingdom

Synopsis

Low grade paediatric brain tumours are increasingly being targeted by anti-vasculature therapies. It is therefore of particular interest to assess perfusion in these pathologies. We assessed paediatric tumour perfusion using both arterial spin labelling (ASL) and dynamic susceptibility contrast (DSC) on a 3T TX Philips Achieva scanner. Blood flow maps were produced for both techniques where good qualitative agreement was found illustrated by strong, significant pixel-by-pixel correlations. We found that tumour blood flow measured by ASL and DSC significantly correlated (ρ = 0.714, P = 0.047) suggesting ASL can be used instead of DSC for this measurement.

Purpose

The widely accepted brain tumour perfusion imaging technique in adults is Dynamic Susceptibility Contrast (DSC) which tracks a contrast agent through vasculature and tissue for a number of applications[1]. In paediatrics however, the technique presents a number of challenges, namely requirement of a cannula and a power injector in conjunction with obtaining an arterial input function for reproducibility[2]. It would therefore be favourable to use a non-contrast method to image perfusion in children such as Arterial Spin Labelling (ASL)[3]. We assessed correlations in perfusion metrics produced from ASL and DSC in paediatric brain tumour patients with the premise of using ASL as an alternative method.

Methods

Eight ASL and DSC scans were both performed on five paediatric patients with low grade brain tumours on a Philips Achieva 3T TX. Six transverse slices with a thickness of 7 mm, a matrix size of 64 × 64 pixels and an FOV of 240 x 240 mm were acquired. For each slice, eight post labelling delays (PLDs) were acquired, ranging from 200-1600 ms, using a multi-phase LOOK-LOCKER sequence employing a flip angle of 40° and using a single shot EPI readout. The pCASL labelling slab was placed 80 mm below the imaging slices and had duration of 1400 ms. The DSC-MRI scan was a transverse FE-EPI scan (TR / TE = 1865 / 40 ms, field-of-view = 240 x 240 mm, matrix = 96 x 96) with flip angle of 20°. Thirty slices with a slice thickness of 3.5 mm each were acquired to cover the whole brain. Contrast agent was delivered in two stages to minimize T1 effects. The temporal resolution of the DSC scan was 1.86 s which was repeated 60 times. In-house software developed in the Python Programming Language was used for the analysis of data. ASL data was fitted to an equation proposed by Dai et al.[4] where tumour blood flow (TBF) was calculated. For the DSC, an arterial input function was generated manually, converted to concentration time curves and subsequently used to calculate TBF, tumour blood volume (TBV) [2]. Relative perfusion (rTBV and rTBF) were defined as tumour/grey matter values. ROIs were manually drawn on co-registered T2-weighted images for healthy-appearing parietal grey matter and tumours and transferred to the perfusion maps for further statistical analysis using the SPSS statistical package (IBM).

Results

Figure 1 shows example perfusion maps produced both ASL and DSC of a paediatric brain tumour patient. Visual and quantitative assessment of perfusion images of the patients suggested the tumours were hypoperfused compared to grey matter which is consistent with what has been shown of low grade tumours previously[5]. The relationships between the different metrics are demonstrated by the plots in Figure 2 where mean values for ROIs are compared and Spearman correlations with significance values included. ASL_TBF showed a strong correlation with both DSC_TBF and DSC_TBV. A Bland Altman analysis showed that the CBF measurements determined by both techniques agreed well with no bias (Figure 3). On a pixel-by pixel basis for a whole slice ASL_CBF (cerebral blood flow) correlated well with both DSC_CBF (mean across all patients: ρ = 0.459, p = 0.003) and DSC_CBV (mean across all patients: ρ = 0.468, p = 0.00003)(cerebral blood volume). Tumour histograms of ASL_TBF, DSC_TBV and DSC_TBF showed qualitatively similar shapes, an example of which is shown in Figure 4.

Discussion

Qualitatively and quantitatively on a pixelwise basis, the perfusion maps from DSC and ASL agree well which is important for radiological assessment as shown in the included figures. CBF is the primary measure of perfusion using ASL and we have shown that it correlates strongly with values from the DSC in the tumours. The significant correlation between ASL TBF and DSC_TBV is interesting but since these are measures of different physiological parameters, this relationship may not hold for all tumour types. The rTBF measurements did not significantly correlate which we believe is due to high values in the grey matter arising from vessels in the ASL. Both the Bland Altman analysis and qualitative observation of the histograms within tumour ROIs suggest in children that the techniques agree well. This is particularly impressive considering the low perfusion and small range of perfusion values observed in the tumours patients.

Conclusions

We have found that perfusion measurements in low grade paediatric brain tumour patients produced using two different techniques correlate well. This suggests that ASL can provide non-invasive measurements that are equivalent to those provided by DSC, making it a valuable alternative.

Acknowledgements

This study was funded by a Birmingham Children’s Hospital Research Foundation project grant and a grant from Free Radio in conjunction with Help Harry Help Others Charity. We also acknowledge funding from the CRUK and EPSRC Cancer Imaging Programme at the Children’s Cancer and Leukaemia Group (CCLG) in association with the MRC and Department of Health (England) (C7809/A10342). Professor Peet is funded through an NIHR Research Professorship, 13-0053. All scans were acquired at the NIHR 3T research centre.

References

1. Korfiatis P, Erickson B (2014) The basics of diffusion and perfusion imaging in brain tumors. Appl Radiol 43 (7):22-29

2. Withey SB, Novak J, MacPherson L, Peet AC (2015) Arterial input function and gray matter cerebral blood volume measurements in children. J Magn Reson Imaging. doi:10.1002/jmri.25060

3. Alsop DC, Detre JA, Golay X, Gunther M, Hendrikse J, Hernandez-Garcia L, Lu H, Macintosh BJ, Parkes LM, Smits M, van Osch MJ, Wang DJ, Wong EC, Zaharchuk G (2014) Recommended implementation of arterial spin-labeled perfusion MRI for clinical applications: A consensus of the ISMRM perfusion study group and the European consortium for ASL in dementia. Magn Reson Med. doi:10.1002/mrm.25197

4. Dai WY, Robson PM, Shankaranarayanan A, Alsop DC (2012) Reduced resolution transit delay prescan for quantitative continuous arterial spin labeling perfusion imaging. Magnet Reson Med 67 (5):1252-1265. doi:Doi 10.1002/Mrm.23103

5. Yeom KW, Mitchell LA, Lober RM, Barnes PD, Vogel H, Fisher PG, Edwards MS (2014) Arterial spin-labeled perfusion of pediatric brain tumors. AJNR Am J Neuroradiol 35 (2):395-401. doi:10.3174/ajnr.A3670

Figures

A series of MR images acquired from a paediatric patient with a Hypothalamic Glioma. (a) Shows a T2-weighted image, (b) shows a CBV map produced from the DSC scans (c) shows a CBF map produced from the DSC scans and (d) shows a CBF map produced from the ASL scan.

Plots showing correlations between mean perfusion measures in paediatric brain tumours. (a) plots the ASL-rCBF (where rCBF is tumour / grey matter) against the DSC-rCBF, (b) plots the ASL-rCBF against the DSC-rCBV, (c) plots DSC-CBF against ASL-CBF for the tumour ROIs and (d) plots DSC-CBV and ASL-CBF.

Bland Altman plots generated using mean TBF values from regions of interest for all scans using both DSC and ASL. (a) Shows the mean TBF, (b) shows the mean rTBF (tumour/grey matter).

A series of plots showing histograms of TBF and TBV values taken from a tumour ROI from a paediatric patient. (a) shows the TBF values generated from a ASL scan. (b) shows the TBF values generated from a DSC scan. (c) shows TBV values generated from a DSC scan.



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