Cancer imaging phenomics toolkit: quantitative imaging analytics for precision diagnostics and predictive modeling of clinical outcome

Abstract. The growth of multiparametric imaging protocols has paved the way for quantitative imaging phenotypes that predict treatment response and clinical outcome, reflect underlying cancer molecular characteristics and spatiotemporal heterogeneity, and can guide personalized treatment planning. This growth has underlined the need for efficient quantitative analytics to derive high-dimensional imaging signatures of diagnostic and predictive value in this emerging era of integrated precision diagnostics. This paper presents cancer imaging phenomics toolkit (CaPTk), a new and dynamically growing software platform for analysis of radiographic images of cancer, currently focusing on brain, breast, and lung cancer. CaPTk leverages the value of quantitative imaging analytics along with machine learning to derive phenotypic imaging signatures, based on two-level functionality. First, image analysis algorithms are used to extract comprehensive panels of diverse and complementary features, such as multiparametric intensity histogram distributions, texture, shape, kinetics, connectomics, and spatial patterns. At the second level, these quantitative imaging signatures are fed into multivariate machine learning models to produce diagnostic, prognostic, and predictive biomarkers. Results from clinical studies in three areas are shown: (i) computational neuro-oncology of brain gliomas for precision diagnostics, prediction of outcome, and treatment planning; (ii) prediction of treatment response for breast and lung cancer, and (iii) risk assessment for breast cancer.

[1]  Ragini Verma,et al.  Assessing connectivity related injury burden in diffuse traumatic brain injury , 2017, Human brain mapping.

[2]  B. Keller,et al.  Preliminary evaluation of the publicly available Laboratory for Breast Radiodensity Assessment (LIBRA) software tool: comparison of fully automated area and volumetric density measures in a case–control study with digital mammography , 2015, Breast Cancer Research.

[3]  Bjoern H. Menze,et al.  Brainlesion: Glioma, Multiple Sclerosis, Stroke and Traumatic Brain Injuries , 2015, Lecture Notes in Computer Science.

[4]  Christos Davatzikos,et al.  NIMG-11. HIGHLY-EXPRESSED WILD-TYPE EGFR AND EGFRvIII MUTANT GLIOBLASTOMAS HAVE SIMILAR MRI SIGNATURE, CONSISTENT WITH DEEP PERITUMORAL INFILTRATION , 2016 .

[5]  S. Gabriel,et al.  Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. , 2010, Cancer cell.

[6]  Luke Macyszyn,et al.  Individualized Map of White Matter Pathways: Connectivity-Based Paradigm for Neurosurgical Planning. , 2016, Neurosurgery.

[7]  J. Friedman Greedy function approximation: A gradient boosting machine. , 2001 .

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

[9]  J. Friedman Stochastic gradient boosting , 2002 .

[10]  Ahmed Bilal Ashraf,et al.  Identification of intrinsic imaging phenotypes for breast cancer tumors: preliminary associations with gene expression profiles. , 2014, Radiology.

[11]  Christos Davatzikos,et al.  Population-based MRI atlases of spatial distribution are specific to patient and tumor characteristics in glioblastoma , 2016, NeuroImage: Clinical.

[12]  Dimitrios Makris,et al.  Fast semi-automatic segmentation of focal liver lesions in contrast-enhanced ultrasound, based on a probabilistic model , 2017, Comput. methods Biomech. Biomed. Eng. Imaging Vis..

[13]  Luke Macyszyn,et al.  Imaging patterns predict patient survival and molecular subtype in glioblastoma via machine learning techniques. , 2016, Neuro-oncology.

[14]  Christos Davatzikos,et al.  MPTH-02. EXTRACELLULAR EGFR289 ACTIVATING MUTATIONS CONFER POORER SURVIVAL AND SUGGEST ENHANCED MOTILITY IN PRIMARY GBMs , 2016 .

[15]  Rachid Deriche,et al.  Unsupervised white matter fiber clustering and tract probability map generation: Applications of a Gaussian process framework for white matter fibers , 2010, NeuroImage.

[16]  Jayaram K. Udupa,et al.  New variants of a method of MRI scale standardization , 2000, IEEE Transactions on Medical Imaging.

[17]  Bilwaj Gaonkar,et al.  Breast DCE-MRI Kinetic Heterogeneity Tumor Markers: Preliminary Associations With Neoadjuvant Chemotherapy Response1 , 2015, Translational oncology.

[18]  Christos Davatzikos,et al.  An image-driven parameter estimation problem for a reaction–diffusion glioma growth model with mass effects , 2008, Journal of mathematical biology.

[19]  Carsten Denkert,et al.  Response-guided neoadjuvant chemotherapy for breast cancer. , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[20]  Christos Davatzikos,et al.  In Vivo Detection of EGFRvIII in Glioblastoma via Perfusion Magnetic Resonance Imaging Signature Consistent with Deep Peritumoral Infiltration: The ϕ-Index , 2017, Clinical Cancer Research.

[21]  Christos Davatzikos,et al.  NIMG-05IDENTIFICATION OF IMAGING SIGNATURES OF THE EPIDERMAL GROWTH FACTOR RECEPTOR VARIANT III (EGFRvIII) IN GLIOBLASTOMA , 2015 .

[22]  T. Cloughesy,et al.  Probabilistic Radiographic Atlas of Glioblastoma Phenotypes , 2013, American Journal of Neuroradiology.

[23]  Julia White,et al.  Neoadjuvant therapy for breast cancer: controversies in clinical trial design and standard of care. , 2015, American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting.

[24]  Christos Davatzikos,et al.  NIMG-20. IMAGING PATTERN ANALYSIS REVEALS THREE DISTINCT PHENOTYPIC SUBTYPES OF GBM WITH DIFFERENT SURVIVAL RATES , 2016 .

[25]  Matti Pietikäinen,et al.  Multiresolution Gray-Scale and Rotation Invariant Texture Classification with Local Binary Patterns , 2002, IEEE Trans. Pattern Anal. Mach. Intell..

[26]  Yuanjie Zheng,et al.  Parenchymal texture analysis in digital mammography: robust texture feature identification and equivalence across devices , 2015, Journal of medical imaging.

[27]  Luke Macyszyn,et al.  Pattern analysis of dynamic susceptibility contrast-enhanced MR imaging demonstrates peritumoral tissue heterogeneity. , 2014, Radiology.

[28]  Christos Davatzikos,et al.  Brain--Tumor Interaction Biophysical Models for Medical Image Registration , 2008, SIAM J. Sci. Comput..

[29]  Xiaoou Tang,et al.  Texture information in run-length matrices , 1998, IEEE Trans. Image Process..

[30]  Xavier Geets,et al.  Radiomics applied to lung cancer: a review , 2016 .

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

[32]  Vandana Dialani,et al.  Role of Imaging in Neoadjuvant Therapy for Breast Cancer , 2015, Annals of Surgical Oncology.

[33]  G. Biros,et al.  Imaging Surrogates of Infiltration Obtained Via Multiparametric Imaging Pattern Analysis Predict Subsequent Location of Recurrence of Glioblastoma. , 2016, Neurosurgery.

[34]  Mitchell D Schnall,et al.  Neoadjuvant Chemotherapy for Breast Cancer: Functional Tumor Volume by MR Imaging Predicts Recurrence-free Survival-Results from the ACRIN 6657/CALGB 150007 I-SPY 1 TRIAL. , 2016, Radiology.

[35]  Christos Davatzikos,et al.  Advancing The Cancer Genome Atlas glioma MRI collections with expert segmentation labels and radiomic features , 2017, Scientific Data.

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

[37]  L. Esserman,et al.  Locally advanced breast cancer: MR imaging for prediction of response to neoadjuvant chemotherapy--results from ACRIN 6657/I-SPY TRIAL. , 2012, Radiology.

[38]  Thomas E. Yankeelov,et al.  Current and Future Trends in Magnetic Resonance Imaging Assessments of the Response of Breast Tumors to Neoadjuvant Chemotherapy , 2010, Journal of oncology.

[39]  E. V. van Beek,et al.  Radiomics and its emerging role in lung cancer research, imaging biomarkers and clinical management: State of the art. , 2017, European journal of radiology.

[40]  M. Cronin,et al.  Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[41]  Tej D. Azad,et al.  Magnetic resonance image features identify glioblastoma phenotypic subtypes with distinct molecular pathway activities , 2015, Science Translational Medicine.

[42]  B. Keller,et al.  Estimation of breast percent density in raw and processed full field digital mammography images via adaptive fuzzy c-means clustering and support vector machine segmentation. , 2012, Medical physics.

[43]  Ragini Verma,et al.  Automated tract extraction via atlas based Adaptive Clustering , 2014, NeuroImage.

[44]  Rachid Deriche,et al.  Unsupervised automatic white matter fiber clustering using a Gaussian mixture model , 2012, 2012 9th IEEE International Symposium on Biomedical Imaging (ISBI).

[45]  Robert M. Haralick,et al.  Textural Features for Image Classification , 1973, IEEE Trans. Syst. Man Cybern..

[46]  Dinggang Shen,et al.  Hierarchical Fiber Clustering Based on Multi-Scale Neuroanatomical Features , 2010, MIAR.

[47]  Michael D. Feldman,et al.  A Multichannel Markov Random Field Approach for Automated Segmentation of Breast Cancer Tumor in DCE-MRI Data Using Kinetic Observation Model , 2011, MICCAI.

[48]  C. Crainiceanu,et al.  Statistical normalization techniques for magnetic resonance imaging , 2014, NeuroImage: Clinical.

[49]  El Naqa,et al.  A radiomics model from joint FDG-PET and MRI texture features for the prediction of lung metastases in soft-tissue sarcomas of the extremities , 2015 .

[50]  Luke Macyszyn,et al.  Addressing the Challenge of Edema in Fiber Tracking , 2014 .

[51]  Bilwaj Gaonkar,et al.  GLISTRboost: Combining Multimodal MRI Segmentation, Registration, and Biophysical Tumor Growth Modeling with Gradient Boosting Machines for Glioma Segmentation , 2015, Brainles@MICCAI.

[52]  W. Eric L. Grimson,et al.  A unified framework for clustering and quantitative analysis of white matter fiber tracts , 2008, Medical Image Anal..

[53]  Yuanjie Zheng,et al.  Parenchymal texture analysis in digital mammography: A fully automated pipeline for breast cancer risk assessment. , 2015, Medical physics.

[54]  Christos Davatzikos,et al.  Segmentation of Gliomas in Pre-operative and Post-operative Multimodal Magnetic Resonance Imaging Volumes Based on a Hybrid Generative-Discriminative Framework , 2016, BrainLes@MICCAI.

[55]  Carl-Fredrik Westin,et al.  Clustering Fiber Traces Using Normalized Cuts , 2004, MICCAI.

[56]  E. Conant,et al.  Deformable registration for quantifying longitudinal tumor changes during neoadjuvant chemotherapy , 2015, Magnetic resonance in medicine.

[57]  Luke Macyszyn,et al.  Improving White Matter Tractography by Resolving the Challenges of Edema , 2013 .

[58]  Gideon Blumenthal,et al.  Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis , 2014, The Lancet.

[59]  Douglas G Altman,et al.  The logrank test , 2004, BMJ : British Medical Journal.

[60]  M. Pencina,et al.  On the C‐statistics for evaluating overall adequacy of risk prediction procedures with censored survival data , 2011, Statistics in medicine.

[61]  Christos Davatzikos,et al.  GLISTR: Glioma Image Segmentation and Registration , 2012, IEEE Transactions on Medical Imaging.

[62]  H. Aerts The Potential of Radiomic-Based Phenotyping in Precision Medicine: A Review. , 2016, JAMA oncology.

[63]  Christos Davatzikos,et al.  Deformable Registration of Glioma Images Using EM Algorithm and Diffusion Reaction Modeling , 2011, IEEE Transactions on Medical Imaging.

[64]  C. Westin,et al.  A method for clustering white matter fiber tracts. , 2006, AJNR. American journal of neuroradiology.

[65]  Elisa Sayrol Clols,et al.  3D convolutional neural networks for brain tumor segmentation , 2016 .

[66]  E. Conant,et al.  Beyond breast density: a review on the advancing role of parenchymal texture analysis in breast cancer risk assessment , 2016, Breast Cancer Research.

[67]  Christos Davatzikos,et al.  NIMG-59. RADIOLOGIC SUBTYPES OF GLIOBLASTOMA CALCULATED VIA MULTI-PARAMETRIC IMAGING SIGNATURES REVEAL COMPLEMENTARY INFORMATION TO CURRENT WHO CLASSIFICATION , 2017 .

[68]  Stephen M. Smith,et al.  SUSAN—A New Approach to Low Level Image Processing , 1997, International Journal of Computer Vision.

[69]  Nikos Paragios,et al.  DRAMMS: Deformable Registration via Attribute Matching and Mutual-Saliency Weighting , 2009, IPMI.

[70]  Stuart A. Taylor,et al.  Imaging biomarker roadmap for cancer studies , 2016, Nature Reviews Clinical Oncology.