Signal intensity analysis of ecological defined habitat in soft tissue sarcomas to predict metastasis development

Magnetic Resonance Imaging (MRI) is the standard of care in the clinic for diagnosis and follow up of Soft Tissue Sarcomas (STS) which presents an opportunity to explore the heterogeneity inherent in these rare tumors. Tumor heterogeneity is a challenging problem to quantify and has been shown to exist at many scales, from genomic to radiomic, existing both within an individual tumor, between tumors from the same primary in the same patient and across different patients. In this paper, we propose a method which focuses on spatially distinct sub-regions or habitats in the diagnostic MRI of patients with STS by using pixel signal intensity. Habitat characteristics likely represent areas of differing underlying biology within the tumor, and delineation of these differences could provide clinically relevant information to aid in selecting a therapeutic regimen (chemotherapy or radiation). To quantify tumor heterogeneity, first we assay intra-tumoral segmentations based on signal intensity and then build a spatial mapping scheme from various MRI modalities. Finally, we predict clinical outcomes, using in this paper the appearance of distant metastasis - the most clinically meaningful endpoint. After tumor segmentation into high and low signal intensities, a set of quantitative imaging features based on signal intensity is proposed to represent variation in habitat characteristics. This set of features is utilized to predict metastasis in a cohort of STS patients. We show that this framework, using only pre-therapy MRI, predicts the development of metastasis in STS patients with 72.41% accuracy, providing a starting point for a number of clinical hypotheses.

[1]  Pawel Badura,et al.  4D Segmentation of Ewing’s Sarcoma in MR Images , 2010 .

[2]  D. Longo,et al.  Tumor heterogeneity and personalized medicine. , 2012, The New England journal of medicine.

[3]  Robert J. Gillies,et al.  Using features from tumor subregions of breast DCE-MRI for estrogen receptor status prediction , 2014, 2014 IEEE International Conference on Systems, Man, and Cybernetics (SMC).

[4]  Mukesh A. Zaveri,et al.  Region Based Image Fusion for Detection of Ewing Sarcoma , 2009, 2009 Seventh International Conference on Advances in Pattern Recognition.

[5]  Hiroyuki Honda,et al.  Cancer diagnosis marker extraction for soft tissue sarcomas based on gene expression profiling data by using projective adaptive resonance theory (PART) filtering method , 2006, BMC Bioinformatics.

[6]  Sheila Weinmann,et al.  Use of diagnostic imaging studies and associated radiation exposure for patients enrolled in large integrated health care systems, 1996-2010. , 2012, JAMA.

[7]  N. Otsu A threshold selection method from gray level histograms , 1979 .

[8]  Hans-Peter Meinzer,et al.  Bildverarbeitung für die Medizin 1999 , 1999 .

[9]  Jan Sijbers,et al.  Machine learning study of several classifiers trained with texture analysis features to differentiate benign from malignant soft‐tissue tumors in T1‐MRI images , 2010, Journal of magnetic resonance imaging : JMRI.

[10]  William Stafford Noble,et al.  Classification of clear-cell sarcoma as a subtype of melanoma by genomic profiling. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[11]  Michael Egmont-Petersen,et al.  Segmentation of Dynamic Contrast-Enhanced MR-Images of Post Chemotherapy Ewing's Sarcoma with a Pharmacokinetic Model and a Neural Network , 1999, Bildverarbeitung für die Medizin.

[12]  Robert J. Gillies,et al.  Prediction of treatment outcome in soft tissue sarcoma based on radiologically defined habitats , 2015, Medical Imaging.

[13]  I. 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, Physics in medicine and biology.

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

[15]  Debyani Chakravarty,et al.  Intratumoral heterogeneity of receptor tyrosine kinases EGFR and PDGFRA amplification in glioblastoma defines subpopulations with distinct growth factor response , 2012, Proceedings of the National Academy of Sciences.

[16]  Robert J. Gillies,et al.  Decoding brain cancer dynamics: a quantitative histogram-based approach using temporal MRI , 2015, Medical Imaging.

[17]  Wilson Roa,et al.  A local contrast based approach to threshold segmentation for PET target volume delineation. , 2006, Medical physics.

[18]  L. Pusztai,et al.  Cancer heterogeneity: implications for targeted therapeutics , 2013, British Journal of Cancer.

[19]  Abhijit J Chaudhari,et al.  Semi-automated volumetric quantification of tumor necrosis in soft tissue sarcoma using contrast-enhanced MRI. , 2012, Anticancer research.

[20]  N. McGranahan,et al.  The causes and consequences of genetic heterogeneity in cancer evolution , 2013, Nature.

[21]  Patrick Granton,et al.  Radiomics: extracting more information from medical images using advanced feature analysis. , 2012, European journal of cancer.

[22]  A. Skubitz,et al.  Identification of heterogeneity among soft tissue sarcomas by gene expression profiles from different tumors , 2008, Journal of Translational Medicine.

[23]  H. Hassan,et al.  Primary retroperitoneal synovial sarcoma in CT and MRI , 2010, Urology annals.

[24]  Laurel Beckett,et al.  Comparison of two-dimensional and three-dimensional iterative watershed segmentation methods in hepatic tumor volumetrics. , 2008, Medical physics.

[25]  F. Turkheimer,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 .

[26]  Hugh D. Curtin,et al.  Parapharyngeal and Masticator Space Lesions , 2011 .

[27]  R. Gillies,et al.  Quantitative imaging in cancer evolution and ecology. , 2013, Radiology.

[28]  Robert Koprowski,et al.  Machine learning, medical diagnosis, and biomedical engineering research - commentary , 2014, BioMedical Engineering OnLine.

[29]  Teruaki Oka,et al.  Cell nucleus segmentation of skin tumor using image processing , 2001, 2001 Conference Proceedings of the 23rd Annual International Conference of the IEEE Engineering in Medicine and Biology Society.