Suhail Pathan Parvaze1, Mamta Gupta2, Anup Singh3, Rana Patir4, Sunita Ahlawat2, Madhura Ingalhalikar5, Neha Vats3, and Rakesh Kumar Gupta2
1Philips Innovation Campus, Bangalore, India, 2Fortis Memorial Research Institute, Gurgaon, India, 3Indian Institute of Technology, New Delhi, India, 4Department of Neurosurgery, Fortis Memorial Research Institute, Gurgaon, India, 5Symbiosis Center for Medical Image analysis, Symbiosis International University, Pune, India
Synopsis
This work aimed at identifying radiomic
signatures that discriminate glioblastoma sub-regions ( enhancing tumor, non-enhancing,
necrosis and edema) using DCE T1 perfusion based post contrast MRI. Results demonstrated
texture features that delineate the four regions as well as separate the
tumoral region from normative white matter. These radiomic signatures can be
further investigated to gain deeper understanding of tumor progression and
recurrence.
Introduction
Glioblastoma (GBM)
is the most common malignant brain tumor. Regardless of maximal safe surgery
plus radiation therapy and chemotherapy, the prognosis of patients with GBM
remains poor [1]. Since, the heterogeneity of GBM contributes to its poor diagnosis which
can be, to some extent, attributed to its excessive heterogeneity. Biopsy samples only provide information
about the tumor that is limited to the biopsy site and do not capture the
complete spatial heterogeneity of the entire tumor. Non-invasive techniques can
be developed to assess the heterogeneity that can reflect tumor biological
properties more comprehensively. Investigations of texture variations in the tumor
sub regions with emphasis on deriving radiomic signature reported to be
challenging but essential in the diagnosis and prognostic studies involving
multi-parametric MRI studies [2-3]. Machine learning approaches were used in
diagnosis, prognosis, recurrence prediction and glioma grading studies [4-6]. Limited
studies are available that depicts the prominent texture features in tumor sub
regions. This work aims at identifying a radiomic signature to discriminate
tumoral region from normative white matter (NAWM) as well as a radiomic differential
marker for each sub-region of the tumor that can be pursued to assess
progression and recurrence and in turn support treatment planning and
optimization. Specifically, we aim to study the predictive potential of fully
three-dimensional (3D) textural heterogeneity in perfusion driven segmented
tumor sub-region masks on T1 post contrast image and 2) To identify any
prominent texture based differential biomarker in the tumor sub region.
Methods
In this study 40 Surgery
naïve histological proven Glioblastoma
(GBM) brain tumor subjects were considered. Multimodal image acquisition was
performed on Philips Ingenia 3T scanner with a 15-channel head coil. DCE T1-perfusion MRI data analysis was done
using in-house code. T1 perfusion parameters (CBV_NorrWM_Corr, CBF_Norr_WM,
Ktrans, Ve, Vp) were computed [7]. Tumor subregions namely contrast enhancing
tumor (ET) and Necrosis (NEC) was delineated with the aid of post contrast (T1GD)
sequence and FLAIR images. Further, tumor subregions namely, non-enhancing
tumor (NET) and edema (ED were delineated using FLAIR sequence and SVM
classifier [7]. Further, a two dimensional binary masks was extracted for the
whole tumor manually from the normal appearing region in all the tumor slices for
each subject and considered as normative tissue. Radiomics based feature
extraction was implemented using PyRadiomics 2.2.0 library [8]. 2D ROIs were converted
to volumetric representation for radiomics feature extraction [9]. Radiomics
features such as statistical features, Gray-Level Co-occurrence Matrix (GLCM),
Gray-Level dependence matrix (GLDM), Gray Level Run Length Matrix (GLRLM), Gray
Level Size Zone Matrix (GLSZM) and Neighboring Gray Tone Difference Matrix
(NGTDM) along with shape features were computed. Shape features were not
considered in this study as the prime focus is to understand the texture
variations in the tumor sub regions. For each tumor region 106 radiomics
features were computed. Same texture features were also extracted from the normative
region [8]. Random forest based feature selection algorithm was implemented to
extract most prominent features [10].
Random forest based classifier was further implemented to train 60% (24
subjects) of the data and the 40% (16 subjects) were held out for testing. Results
The pipeline of the work implemented as part of this study is
demonstrated in Figure 1. The input sequences and feature maps overlaid on the
representative images are shown in Figure 2. The overall test accuracy obtained
was 73%. Table 1 displays the top ranked features, which were mainly texture
based features. The classification accuracy across the tumor sub regions is
shown in the Table 2. Texture features of the ET showed high accuracy from the ED
and NEC regions, however, a subtle differentiation was observed from NET tumor
region. Figure 3(a) represents comparison of NGTDM coarseness texture value.
Higher values observed in the case of edema compared to NAWM and tumor sub regions.
Especially ET and NET values seems to be very low suggesting uniformity is
highly distorted. Figure 3(b) depicts GLCM joint entropy, which
indicates ET region has highly randomized texture.Discussions and Conclusions
Results obtained in
this study indicates that texture features obtained using PyRadiomics tool
serve to differentiate the texture variation among the tumor subregions in
glioblastoma. The increase in NGTDM coarseness in ED defines the uniformity in
this particular region. A poor texture feature differentiation and low
classification accuracy between ED and NEC regions might be due to the
uniformity of features present in both the regions. However, the marginal
accuracy between the ET and NET suggest that there exist common texture
properties between the two which could be due to higher vascularisation. This
study can be considered to be a first step in identifying radiomic biomarkers
for GBM tissue types of texture features using Radiomics and machine learning
approaches that appears to be differentiating tumor subregions from normal region
and among themselves in the glioblastoma patients. Acknowledgements
No acknowledgement found.References
1. Blumenthal DT, Artzi M, Liberman G, et al. Classification of high-grade glioma into tumor and nontumor components using support vector machine. American Journal of Neuroradiology. 2017;38:908-14. 2. Kassner RE, Thornhill RE. Texture Analysis: A Review of Neurologic MR Imaging Applications. AJNR Am J Neuroradiol. 2010; 31: 809-816. 3. Galleno G, Bonilha L, Li LM, Cendes F. Texture analysis of medical images. Clin Radiol. 2004; 59:1061-1069. 4. Lasocki A, Gaillard F. Non-contrast-enhancing tumor: a new frontier in glioblastoma research. American Journal of Neuroradiology. 2019 ;40:758-65. 5. Ion-Mărgineanu A, Van Cauter S, Sima DM, Maes F et al. Classifying glioblastoma multiforme follow-up progressive vs. responsive forms using multi-parametric MRI features. Frontiers in neuroscience. 2017 ; 10:615. 6. Van der Voort SR, Incekara F, Wijnenga MM et al. Predicting the 1p/19q co-deletion status of presumed low grade glioma with an externally validated machine learning algorithm. Clinical Cancer Research. 2019;1127. 7. Sengupta A, Agarwal S, Gupta PK, et al. On differentiation between vasogenic edema and non-enhancing tumor in high-grade glioma patients using a support vector machine classifier based upon pre and post-surgery MRI images. European journal of radiology. 2018;106:199-208 8. Van Griethuysen JJ, Fedorov A, Parmar C, Hosny A, Aucoin N, Narayan V, Beets-Tan RG, Fillion-Robin JC, Pieper S, Aerts HJ. Computational radiomics system to decode the radiographic phenotype. Cancer research. 2017 ;77:104-7. 9. Xu J, Ma X, Tian Z et al. Glioblastoma Multiforme and Anaplastic Astrocytoma: Differentiation using MRI Texture Analysis. Frontiers in oncology. 2019; 9:876. 10. Beig N, Patel J, Prasanna P, Hill V et al. Radiogenomic analysis of hypoxia pathway is predictive of overall survival in Glioblastoma. Scientific reports. 2018;8:7.