Tumor image-derived texture features are associated with CD3 T-cell infiltration status in glioblastoma

This study analyzed magnetic resonance imaging (MRI) scans of Glioblastoma (GB) patients to develop an imaging-derived predictive model for assessing the extent of intratumoral CD3 T-cell infiltration. Pre-surgical T1-weighted post-contrast and T2-weighted Fluid-Attenuated-Inversion-Recovery (FLAIR) MRI scans, with corresponding mRNA expression of CD3D/E/G were obtained through The Cancer Genome Atlas (TCGA) for 79 GB patients. The tumor region was contoured and 86 image-derived features were extracted across the T1-post contrast and FLAIR images. Six imaging features—kurtosis, contrast, small zone size emphasis, low gray level zone size emphasis, high gray level zone size emphasis, small zone high gray level emphasis—were found associated with CD3 activity and used to build a predictive model for CD3 infiltration in an independent data set of 69 GB patients (using a 50-50 split for training and testing). For the training set, the image-based prediction model for CD3 infiltration achieved accuracy of 97.1% and area under the curve (AUC) of 0.993. For the test set, the model achieved accuracy of 76.5% and AUC of 0.847. This suggests a relationship between image-derived textural features and CD3 T-cell infiltration enabling the non-invasive inference of intratumoral CD3 T-cell infiltration in GB patients, with potential value for the radiological assessment of response to immune therapeutics.

[1]  H. Abdollahi,et al.  Test-Retest Reproducibility and Robustness Analysis of Recurrent Glioblastoma MRI Radiomics Texture Features , 2017 .

[2]  Hannah C. Beird,et al.  Genomic and immune heterogeneity are associated with differential responses to therapy in melanoma , 2017, npj Genomic Medicine.

[3]  Raymond Y Huang,et al.  Multimodal MRI features predict isocitrate dehydrogenase genotype in high-grade gliomas , 2017, Neuro-oncology.

[4]  Edward F. Chang,et al.  Tumor evolution of glioma intrinsic gene expression subtype associates with immunological changes in the microenvironment , 2016, bioRxiv.

[5]  Juan J. Martinez,et al.  Evaluation of tumor-derived MRI-texture features for discrimination of molecular subtypes and prediction of 12-month survival status in glioblastoma. , 2015, Medical physics.

[6]  Arvind Rao,et al.  Imaging-genomic pipeline for identifying gene mutations using three-dimensional intra-tumor heterogeneity features , 2015, Journal of medical imaging.

[7]  Lars J. Grimm,et al.  Computational approach to radiogenomics of breast cancer: Luminal A and luminal B molecular subtypes are associated with imaging features on routine breast MRI extracted using computer vision algorithms , 2015, Journal of magnetic resonance imaging : JMRI.

[8]  Philippe Lambin,et al.  Is there a causal relationship between genetic changes and radiomics-based image features? An in vivo preclinical experiment with doxycycline inducible GADD34 tumor cells. , 2015, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[9]  Benjamin Haibe-Kains,et al.  Radiomic feature clusters and Prognostic Signatures specific for Lung and Head & Neck cancer , 2015, Scientific Reports.

[10]  W. Pope Genomics of brain tumor imaging. , 2015, Neuroimaging clinics of North America.

[11]  J.R. Mitchell,et al.  MRI Texture Analysis Predicts p53 Status in Head and Neck Squamous Cell Carcinoma , 2015, American Journal of Neuroradiology.

[12]  Andrea Giovagnoni,et al.  Open source software in a practical approach for post processing of radiologic images , 2015, La radiologia medica.

[13]  R. Korn,et al.  Noninvasive Image Texture Analysis Differentiates K-ras Mutation from Pan-Wildtype NSCLC and Is Prognostic , 2014, PloS one.

[14]  Alejandra Gonzalez-Beltran,et al.  Version 1.1 , 1997 .

[15]  P. Lambin,et al.  Decoding tumour phenotype by noninvasive imaging using a quantitative radiomics approach , 2014, Nature Communications.

[16]  S. Plevritis,et al.  Glioblastoma multiforme: exploratory radiogenomic analysis by using quantitative image features. , 2014, Radiology.

[17]  Peter J. Ell,et al.  Multifunctional Imaging Signature for V-KI-RAS2 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) Mutations in Colorectal Cancer , 2014, The Journal of Nuclear Medicine.

[18]  R. Buist,et al.  Active inflammation increases the heterogeneity of MRI texture in mice with relapsing experimental allergic encephalomyelitis. , 2014, Magnetic resonance imaging.

[19]  R. Gillies,et al.  Radiologically defined ecological dynamics and clinical outcomes in glioblastoma multiforme: preliminary results. , 2014, Translational oncology.

[20]  Neema Jamshidi,et al.  Illuminating radiogenomic characteristics of glioblastoma multiforme through integration of MR imaging, messenger RNA expression, and DNA copy number variation. , 2013, Radiology.

[21]  Chun-Ta Liao,et al.  Textural Features of Pretreatment 18F-FDG PET/CT Images: Prognostic Significance in Patients with Advanced T-Stage Oropharyngeal Squamous Cell Carcinoma , 2013, The Journal of Nuclear Medicine.

[22]  P. Lambin,et al.  Stability of FDG-PET Radiomics features: An integrated analysis of test-retest and inter-observer variability , 2013, Acta oncologica.

[23]  K. Aldape,et al.  Immune Heterogeneity of Glioblastoma Subtypes: Extrapolation from the Cancer Genome Atlas , 2013, Cancer Immunology Research.

[24]  Benjamin M Ellingson,et al.  Identifying the mesenchymal molecular subtype of glioblastoma using quantitative volumetric analysis of anatomic magnetic resonance images. , 2013, Neuro-oncology.

[25]  Klaus H. Maier-Hein,et al.  The Medical Imaging Interaction Toolkit: challenges and advances , 2013, International Journal of Computer Assisted Radiology and Surgery.

[26]  Bernard Fertil,et al.  Shape and Texture Indexes Application to Cell nuclei Classification , 2013, Int. J. Pattern Recognit. Artif. Intell..

[27]  T. Cloughesy,et al.  Relationship between Tumor Enhancement, Edema, IDH1 Mutational Status, MGMT Promoter Methylation, and Survival in Glioblastoma , 2012, American Journal of Neuroradiology.

[28]  Lynda Chin,et al.  Emerging insights into the molecular and cellular basis of glioblastoma. , 2012, Genes & development.

[29]  M. Guiou,et al.  Novel Therapies in Glioblastoma , 2012, Neurology research international.

[30]  C. Good,et al.  Measurements of heterogeneity in gliomas on computed tomography relationship to tumour grade , 2012, Journal of Neuro-Oncology.

[31]  G. D. de Bock,et al.  The prognostic influence of tumour-infiltrating lymphocytes in cancer: a systematic review with meta-analysis , 2011, British Journal of Cancer.

[32]  Xavier Robin,et al.  pROC: an open-source package for R and S+ to analyze and compare ROC curves , 2011, BMC Bioinformatics.

[33]  S. Nelson,et al.  Gene Expression Profile Correlates with T-Cell Infiltration and Relative Survival in Glioblastoma Patients Vaccinated with Dendritic Cell Immunotherapy , 2010, Clinical Cancer Research.

[34]  I. Yang,et al.  CD8+ T-cell infiltrate in newly diagnosed glioblastoma is associated with long-term survival , 2010, Journal of Clinical Neuroscience.

[35]  Witold R. Rudnicki,et al.  Feature Selection with the Boruta Package , 2010 .

[36]  T. Gajewski,et al.  Gene Signature in Melanoma Associated With Clinical Activity: A Potential Clue to Unlock Cancer Immunotherapy , 2010, Cancer journal.

[37]  Susan M. Chang,et al.  Recent advances in therapy for glioblastoma. , 2010, Archives of neurology.

[38]  Sylvia Drabycz,et al.  An analysis of image texture, tumor location, and MGMT promoter methylation in glioblastoma using magnetic resonance imaging , 2010, NeuroImage.

[39]  Hod Lipson,et al.  Distilling Free-Form Natural Laws from Experimental Data , 2009, Science.

[40]  Balaji Ganeshan,et al.  Colorectal cancer: texture analysis of portal phase hepatic CT images as a potential marker of survival. , 2009, Radiology.

[41]  David S. Yang,et al.  Incidence and Prognostic Impact of FoxP3+ Regulatory T Cells in Human Gliomas , 2008, Clinical Cancer Research.

[42]  R. Jacobs,et al.  Imaging Immune Response In vivo: Cytolytic Action of Genetically Altered T Cells Directed to Glioblastoma Multiforme , 2008, Clinical Cancer Research.

[43]  D. Demetrick,et al.  The Use of Magnetic Resonance Imaging to Noninvasively Detect Genetic Signatures in Oligodendroglioma , 2008, Clinical Cancer Research.

[44]  K. Aldape,et al.  Identification of noninvasive imaging surrogates for brain tumor gene-expression modules , 2008, Proceedings of the National Academy of Sciences.

[45]  Florian Jäger,et al.  A Comparison of Five Methods for Signal Intensity Standardization in MRI , 2008, Bildverarbeitung für die Medizin.

[46]  J. Smirniotopoulos,et al.  Patterns of contrast enhancement in the brain and meninges. , 2007, Radiographics : a review publication of the Radiological Society of North America, Inc.

[47]  M. Lesniak,et al.  CD4+CD25+FoxP3+ T-cell infiltration and heme oxygenase-1 expression correlate with tumor grade in human gliomas , 2007, Journal of Neuro-Oncology.

[48]  L. Hakansson,et al.  Biochemotherapy of metastatic malignant melanoma. Predictive value of tumour-infiltrating lymphocytes , 2001, British Journal of Cancer.

[49]  Matthew J. McAuliffe,et al.  Medical Image Processing, Analysis and Visualization in clinical research , 2001, Proceedings 14th IEEE Symposium on Computer-Based Medical Systems. CBMS 2001.

[50]  Ron Kikinis,et al.  Markov random field segmentation of brain MR images , 1997, IEEE Transactions on Medical Imaging.

[51]  Robert King,et al.  Textural features corresponding to textural properties , 1989, IEEE Trans. Syst. Man Cybern..

[52]  Mary M. Galloway,et al.  Texture analysis using gray level run lengths , 1974 .