Deep learning and radiomics: the utility of Google TensorFlow™ Inception in classifying clear cell renal cell carcinoma and oncocytoma on multiphasic CT

PurposeCurrently, all solid enhancing renal masses without microscopic fat are considered malignant until proven otherwise and there is substantial overlap in the imaging findings of benign and malignant renal masses, particularly between clear cell RCC (ccRCC) and benign oncocytoma (ONC). Radiomics has attracted increased attention for its utility in pre-operative work-up on routine clinical images. Radiomics based approaches have converted medical images into mineable data and identified prognostic imaging signatures that machine learning algorithms can use to construct predictive models by learning the decision boundaries of the underlying data distribution. The TensorFlow™ framework from Google is a state-of-the-art open-source software library that can be used for training deep learning neural networks for performing machine learning tasks. The purpose of this study was to investigate the diagnostic value and feasibility of a deep learning-based renal lesion classifier using open-source Google TensorFlow™ Inception in differentiating ccRCC from ONC on routine four-phase MDCT in patients with pathologically confirmed renal masses.MethodsWith institutional review board approval for this 1996 Health Insurance Portability and Accountability Act compliant retrospective study and a waiver of informed consent, we queried our institution’s pathology, clinical, and radiology databases for histologically proven cases of ccRCC and ONC obtained between January 2000 and January 2016 scanned with a an intravenous contrast-enhanced four-phase renal mass protocol (unenhanced (UN), corticomedullary (CM), nephrographic (NP), and excretory (EX) phases). To extract features to be used for the machine learning model, the entire renal mass was contoured in the axial plane in each of the four phases, resulting in a 3D volume of interest (VOI) representative of the entire renal mass. We investigated thirteen different approaches to convert the acquired VOI data into a set of images that adequately represented each tumor which was used to train the final layer of the neural network model. Training was performed over 4000 iterations. In each iteration, 90% of the data were designated as training data and the remaining 10% served as validation data and a leave-one-out cross-validation scheme was implemented. Accuracy, sensitivity, specificity, positive (PPV) and negative predictive (NPV) values, and CIs were calculated for the classification of the thirteen processing modes.ResultsWe analyzed 179 consecutive patients with 179 lesions (128 ccRCC and 51 ONC). The ccRCC cohort had a mean size of 3.8 cm (range 0.8–14.6 cm) and the ONC cohort had a mean lesion size of 3.9 cm (range 1.0–13.1 cm). The highest specificity and PPV (52.9% and 80.3%, respectively) were achieved in the EX phase when we analyzed the single mid-slice of the tumor in the axial, coronal and sagittal plane, and when we increased the number of mid-slices of the tumor to three, with an accuracy of 75.4%, which also increased the sensitivity to 88.3% and the PPV to 79.6%. Using the entire tumor volume also showed that classification performance was best in the EX phase with an accuracy of 74.4%, a sensitivity of 85.8% and a PPV of 80.1%. When the entire tumor volume, plus mid-slices from all phases and all planes presented as tiled images, were submitted to the final layer of the neural network we achieved a PPV of 82.5%.ConclusionsThe best classification result was obtained in the EX phase among the thirteen classification methods tested. Our proof of concept study is the first step towards understanding the utility of machine learning in the differentiation of ccRCC from ONC on routine CT images. We hope this could lead to future investigation into the development of a multivariate machine learning model which may augment our ability to accurately predict renal lesion histology on imaging.

[1]  Nobhojit Roy,et al.  The Global Burden of Cancer 2013. , 2015, JAMA oncology.

[2]  Isabelle Guyon,et al.  An Introduction to Variable and Feature Selection , 2003, J. Mach. Learn. Res..

[3]  Kousei Ishigami,et al.  Imaging spectrum of renal oncocytomas: a pictorial review with pathologic correlation , 2014, Insights into Imaging.

[4]  E. Wallen,et al.  Associations between Tumor Vascularity, Vascular Endothelial Growth Factor Expression and PET/MRI Radiomic Signatures in Primary Clear-Cell–Renal-Cell-Carcinoma: Proof-of-Concept Study , 2017, Scientific Reports.

[5]  Gangning Liang,et al.  Quantitative Contour Analysis as an Image-based Discriminator Between Benign and Malignant Renal Tumors. , 2018, Urology.

[6]  Zeenia Jagga,et al.  Classification models for clear cell renal carcinoma stage progression, based on tumor RNAseq expression trained supervised machine learning algorithms , 2014, BMC Proceedings.

[7]  Brian R Herts,et al.  Management of the incidental renal mass. , 2008, Radiology.

[8]  H. Aerts,et al.  Applications and limitations of radiomics , 2016, Physics in medicine and biology.

[9]  Steven S Raman,et al.  Qualitative and quantitative MDCT features for differentiating clear cell renal cell carcinoma from other solid renal cortical masses. , 2014, AJR. American journal of roentgenology.

[10]  Sergey Ioffe,et al.  Rethinking the Inception Architecture for Computer Vision , 2015, 2016 IEEE Conference on Computer Vision and Pattern Recognition (CVPR).

[11]  Simukayi Mutasa,et al.  Convolutional Neural Network Based Breast Cancer Risk Stratification Using a Mammographic Dataset. , 2019, Academic radiology.

[12]  Hongqian Guo,et al.  Percutaneous radiofrequency ablation for renal cell carcinoma vs. partial nephrectomy: Comparison of long-term oncologic outcomes in both clear cell and non-clear cell of the most common subtype. , 2017, Urologic oncology.

[13]  H. Hricak,et al.  Radiogenomics of clear cell renal cell carcinoma: associations between CT imaging features and mutations. , 2013, Radiology.

[14]  P. A. Futreal,et al.  Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. , 2012, The New England journal of medicine.

[15]  Daniel Margolis,et al.  Clear cell renal cell carcinoma: discrimination from other renal cell carcinoma subtypes and oncocytoma at multiphasic multidetector CT. , 2013, Radiology.

[16]  Dimitris Visvikis,et al.  Characterization of PET/CT images using texture analysis: the past, the present… any future? , 2016, European Journal of Nuclear Medicine and Molecular Imaging.

[17]  Jonathan Scalera,et al.  Texture analysis as a radiomic marker for differentiating renal tumors , 2017, Abdominal Radiology.

[18]  Michael S. Bernstein,et al.  ImageNet Large Scale Visual Recognition Challenge , 2014, International Journal of Computer Vision.

[19]  N. Takahashi,et al.  CT and MR imaging for solid renal mass characterization. , 2018, European journal of radiology.

[20]  Erich P Huang,et al.  Radiogenomics of clear cell renal cell carcinoma: preliminary findings of The Cancer Genome Atlas–Renal Cell Carcinoma (TCGA–RCC) Imaging Research Group , 2015, Abdominal Imaging.

[21]  Paul Kinahan,et al.  Radiomics: Images Are More than Pictures, They Are Data , 2015, Radiology.

[22]  C. Nicolau,et al.  Usefulness of MDCT to Differentiate Between Renal Cell Carcinoma and Oncocytoma: Development of a Predictive Model. , 2016, AJR. American journal of roentgenology.

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

[24]  J. Cheville,et al.  Solid renal tumors: an analysis of pathological features related to tumor size. , 2003, The Journal of urology.

[25]  Steven Y Cen,et al.  Differentiation of Predominantly Solid Enhancing Lipid-Poor Renal Cell Masses by Use of Contrast-Enhanced CT: Evaluating the Role of Texture in Tumor Subtyping. , 2018, AJR. American journal of roentgenology.

[26]  R. Leveillee,et al.  Differentiation of oncocytoma and renal cell carcinoma in small renal masses (<4 cm): the role of 4-phase computerized tomography , 2011, World Journal of Urology.

[27]  A. Shinagare,et al.  Advanced Renal Cell Carcinoma: Role of the Radiologist in the Era of Precision Medicine. , 2017, Radiology.

[28]  Yi C. Zhang,et al.  Machine Learning Interface for Medical Image Analysis , 2016, Journal of Digital Imaging.

[29]  Chaya S Moskowitz,et al.  Solid renal cortical tumors: differentiation with CT. , 2007, Radiology.

[30]  P. Lambin,et al.  Machine Learning methods for Quantitative Radiomic Biomarkers , 2015, Scientific Reports.

[31]  Elliot K Fishman,et al.  CT texture analysis of renal masses: pilot study using random forest classification for prediction of pathology. , 2014, Academic radiology.

[32]  P. Pickhardt,et al.  CT Textural Analysis of Large Primary Renal Cell Carcinomas: Pretreatment Tumor Heterogeneity Correlates With Histologic Findings and Clinical Outcomes. , 2016, AJR. American journal of roentgenology.

[33]  Bino Varghese,et al.  Voxel-based whole-lesion enhancement parameters: a study of its clinical value in differentiating clear cell renal cell carcinoma from renal oncocytoma , 2017, Abdominal Radiology.

[34]  Matthew S. Brown,et al.  Quantitative computer-aided diagnostic algorithm for automated detection of peak lesion attenuation in differentiating clear cell from papillary and chromophobe renal cell carcinoma, oncocytoma, and fat-poor angiomyolipoma on multiphasic multidetector computed tomography , 2017, Abdominal Radiology.

[35]  Matthew A. Zapala,et al.  The Radiogenomic Risk Score: Construction of a Prognostic Quantitative, Noninvasive Image-based Molecular Assay for Renal Cell Carcinoma. , 2015, Radiology.

[36]  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.

[37]  M. Götz,et al.  Radiomic Profiling of Glioblastoma: Identifying an Imaging Predictor of Patient Survival with Improved Performance over Established Clinical and Radiologic Risk Models. , 2016, Radiology.

[38]  E. J. Yates,et al.  Machine learning "red dot": open-source, cloud, deep convolutional neural networks in chest radiograph binary normality classification. , 2018, Clinical radiology.

[39]  R. Real,et al.  AUC: a misleading measure of the performance of predictive distribution models , 2008 .

[40]  B. Trock,et al.  Multiphasic enhancement patterns of small renal masses (≤4 cm) on preoperative computed tomography: utility for distinguishing subtypes of renal cell carcinoma, angiomyolipoma, and oncocytoma. , 2012, Urology.

[41]  Andre Dekker,et al.  Radiomics: the process and the challenges. , 2012, Magnetic resonance imaging.

[42]  김종영 구글 TensorFlow 소개 , 2015 .

[43]  Di Dong,et al.  Non-small cell lung cancer: quantitative phenotypic analysis of CT images as a potential marker of prognosis , 2016, Scientific Reports.

[44]  Junmo Kim,et al.  Differentiation of fat‐poor angiomyolipoma from clear cell renal cell carcinoma in contrast‐enhanced MDCT images using quantitative feature classification , 2017, Medical physics.