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 cancers
1. 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 grades
2. 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 FLAIR
3,4.
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 DWI
8, 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 region
10 and from the aging brain
11.
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 atrophy
11.
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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