Non-Gaussian measurements of water diffusion in glioma as a tool for probing tumor heterogeneity and grade.
Fulvio Zaccagna1, Frank Riemer1, Mary McLean2, Andrew N. Priest3, James T. Grist1, Joshua Kaggie1, Sarah Hilborne1, Tomasz Matys1, Martin J. Graves1, Jonathan H. Gillard1, Stephen J. Price4, and Ferdia A. Gallagher1

1Department of Radiology, University of Cambridge, Cambridge, United Kingdom, 2Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom, 3Radiology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom, 4Neurosurgery Unit, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom

Synopsis

Glioma grade and extent of local infiltration are used to guide surgical tumor management. Heterogeneity imaging is a way of assessing the tumor microenvironment, which may improve diagnosis and therapy planning. Diffusion Kurtosis Imaging (DKI) is a novel promising technique that estimates non-Gaussian water diffusion as a measure of heterogeneity. We investigate the use of DKI in glioma as a tool to improve tumor grading and to estimate infiltration. Our preliminary results show a mean kurtosis of 0.56±0.02 in glioblastoma and 1.14±0.07 in normal-appearing white matter. DKI may thus represent a useful tool for estimation of tumor heterogeneity in glioma.

Introduction

Among primary brain tumors, gliomas are the most common and account for nearly 70% of cancers1. MRI is used to locate and characterize these tumors, as well as assist with surgical planning. However, grading of these lesions is challenging because many imaging characteristics overlap with different tumor grades2. Another limitation is the difficulty of evaluating tumor extent. Tumor cells have been shown to extend beyond the limits of contrast enhancement and even up to 2.5cm beyond the hyperintensity seen on either T2-weighted imaging or FLAIR3,4.
Diffusion-Weighted Imaging (DWI) and Diffusion Tensor Imaging (DTI), based on the Gaussian distribution of water movement, are powerful tools to evaluate tumor cellularity and invasiveness. However, water movement is often non-Gaussian, particularly in the context of the heterogeneous tumor microenvironment. To overcome this limitation, a novel technique, based on the non-Gaussian distribution of water movement, has been developed termed Diffusion Kurtosis Imaging (DKI)5–7. DKI has shown better performance in discriminating between low-grade (LGG) and high-grade (HGG) Gliomas compared to DWI8, however there has only been limited research in this area.
The purpose of our study is to characterize the DKI pattern of gliomas, including the peri-tumoral region, and to correlate these to biopsy specimens as well as to explore the utility of DKI in the management of gliomas.

Methods

This work presents the preliminary results from a prospective study, approved by the local ethics committee. DKI was acquired on a 3T MRI system (MR750, GE Healthcare, Waukesha, WI) using an EPI sequence with spectral-spatial excitation. Acquisition parameters were as follows: diffusion encoding directions = 30; b-values = 0, 1000, 2000; TR = 2000ms; TE = 110ms; FOV = 22x22cm; matrix = 128x128; slice thickness = 4mm.
Diffusion parameters were derived following the method proposed by Tabesh using the software DKE (Center for Biomedical Imaging, MUSC, Charleston, SC)9. A neuroradiologist drew all the regions-of-interest (ROIs) using OsiriX (Pixmeo Sarl); T2W-FLAIR and a 3D-T1W sequences were used as guidance for ROI selection. ROIs were drawn in multiple slices around the entire enhancing lesion (including any possible necrosis), the solid component alone, and the surrounding edema; normal-appearing white matter (NAWM) was bilaterally assessed in every slice in the frontal, temporal, occipital and parietal lobe as appropriate resulting in minimum 10 ROIs per region; normal-appearing grey matter (NAGM) was bilaterally assessed in the basal ganglia in every slice resulting in 8 ROIs.

Results

At present, we have successfully scanned a 70 year-old patient with a multifocal GBM (left temporal primary lesion confirmed at histology and a smaller unbiopsied right insular secondary lesion). Mean Kurtosis (MK) values for NAWM were 0.84±0.04 (mean ± standard deviation) [range: 0.75-0.91] in the frontal lobe and 1.14±0.07 [0.99-1.25] in the temporal and parietal lobes; MK values for NAGM were 1.34±0.26 [1.03-1.89]. MK values were 0.56±0.02 [0.53-0.59] for the whole tumor, 0.57±0.02 [0.55-0.60] for the solid component, and 0.63±0.05 [0.56-0.68] for the surrounding edema (Fig. 1 and 2).

Discussion

We present the preliminary data from a prospective study evaluating the role of DKI in improving the characterization of glioma pre-surgically. Although this analysis is limited to a single patient, our data are consistent with previous data from gliomas and peri-tumoral region10 and from the aging brain11.
DKI has the potential to detect changes and heterogeneity in tissue microstructure that are beyond the resolution of conventional MRI. We showed that MK values of GBM are lower than in NAWM. Moreover, DKI in the region of peri-tumoral T2 hyperintensity demonstrated values between that for GBM and NAWM. This could represent an earlier infiltrative stage in which cancer cells are degrading the organized white matter but without macroscopic evidence of anatomical distortion. We excluded the frontal lobe from the analysis because changes in kurtosis have been demonstrated in the aging brain and are thought to reflect the increase of cerebrospinal fluid consequent to increased brain atrophy11.
This study will be continued to determine if changes in diffusional kurtosis can facilitate tumor grading and improve the characterization of tumor extent beyond the area of contrast enhancement.

Conclusion

DKI could represent a complementary non-invasive tool to characterize gliomas and tumor infiltration more accurately, compared to more conventional MRI techniques.

Acknowledgements

This work was supported by the CRUK-EPSRC Cancer Imaging Centre in Cambridge and Manchester (grant no: C197/A16465), the NIHR Cambridge Biomedical Research Centre and the Cambridge Experimental Cancer Medicine Centre (ECMC).

References

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Figures

The box plot shows mean kurtosis (MK) values for Normal Appearing White Matter (NAWM), whole tumor, the solid and enhancing component and the surrounding edema.

Axial mean kurtosis (MK) image (a) and T2-FLAIR image (b). The DKI image demonstrates an area of low MK corresponding to the primary GBM; there is heterogeneity of kurtosis within the lesion and in the surrounding area compatible with tumor infiltration, however the latter has not been confirmed by a targeted biopsy. The second lesion shows a similar pattern of decreased MK values, although slightly higher than the primary lesion. This could represent a different stage of dedifferentiation.



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