Application of hierarchical clustering to multi-parametric MR in prostate: Differentiation of tumor and normal tissue with high accuracy.

PURPOSE Hierarchical clustering (HC), an unsupervised machine learning (ML) technique, was applied to multi-parametric MR (mp-MR) for prostate cancer (PCa). The aim of this study is to demonstrate HC can diagnose PCa in a straightforward interpretable way, in contrast to deep learning (DL) techniques. METHODS HC was constructed using mp-MR including intravoxel incoherent motion, diffusion kurtosis imaging, and dynamic contrast-enhanced MRI from 40 tumor and normal tissues in peripheral zone (PZ) and 23 tumor and normal tissues in transition zone (TZ). HC model was optimized by assessing the combinations of several dissimilarity and linkage methods. Goodness of HC model was validated by internal methods. RESULTS Accuracy for differentiating tumor and normal tissue by optimal HC model was 96.3% in PZ and 97.8% in TZ, comparable to current clinical standards. Relationship between input (DWI and permeability parameters) and output (tumor and normal tissue cluster) was shown by heat maps, consistent with literature. CONCLUSION HC can accurately differentiate PCa and normal tissue, comparable to state-of-the-art diffusion based parameters. Contrary to DL techniques, HC is an operator-independent ML technique producing results that can be interpreted such that the results can be knowledgeably judged.

[1]  H. Merisaari,et al.  Evaluation of different mathematical models for diffusion‐weighted imaging of normal prostate and prostate cancer using high b‐values: A repeatability study , 2015, Magnetic resonance in medicine.

[2]  R. Tibshirani,et al.  Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[3]  Dietmar Cordes,et al.  Hierarchical clustering to measure connectivity in fMRI resting-state data. , 2002, Magnetic resonance imaging.

[4]  D. Atkinson,et al.  Multi-parametric MRI zone-specific diagnostic model performance compared with experienced radiologists for detection of prostate cancer , 2018, European Radiology.

[5]  M. Kantarci,et al.  The evaluation of prostate lesions with IVIM DWI and MR perfusion parameters at 3T MRI , 2018, La radiologia medica.

[6]  B. Taouli,et al.  Multiparametric magnetic resonance imaging for transition zone prostate cancer: essential findings, limitations, and future directions , 2017, Abdominal Radiology.

[7]  Abhishek Das,et al.  Grad-CAM: Visual Explanations from Deep Networks via Gradient-Based Localization , 2016, 2017 IEEE International Conference on Computer Vision (ICCV).

[8]  Enrico W. Coiera,et al.  Automation bias and verification complexity: a systematic review , 2017, J. Am. Medical Informatics Assoc..

[9]  Andreas Lemke,et al.  Investigation of prostate cancer using diffusion-weighted intravoxel incoherent motion imaging. , 2011, Magnetic resonance imaging.

[10]  Michalis Vazirgiannis,et al.  Cluster validity methods: part I , 2002, SGMD.

[11]  Sanjay P Prabhu,et al.  Ethical challenges of machine learning and deep learning algorithms. , 2019, The Lancet. Oncology.

[12]  Eréndira Rendón,et al.  Internal versus External cluster validation indexes , 2011 .

[13]  Hui Xiong,et al.  Understanding of Internal Clustering Validation Measures , 2010, 2010 IEEE International Conference on Data Mining.

[14]  P. Rousseeuw Silhouettes: a graphical aid to the interpretation and validation of cluster analysis , 1987 .

[15]  F. Gallagher,et al.  Diagnostic evaluation of magnetization transfer and diffusion kurtosis imaging for prostate cancer detection in a re-biopsy population , 2017, European Radiology.

[16]  Fei Wang,et al.  Deep learning for healthcare: review, opportunities and challenges , 2018, Briefings Bioinform..

[17]  D. Marquardt An Algorithm for Least-Squares Estimation of Nonlinear Parameters , 1963 .

[18]  K. Ngiam,et al.  Big data and machine learning algorithms for health-care delivery. , 2019, The Lancet. Oncology.

[19]  Sameh A. Salem,et al.  Development of assessment criteria for clustering algorithms , 2009, Pattern Analysis and Applications.

[20]  Jurgen J Fütterer,et al.  Accuracy of multiparametric MRI for prostate cancer detection: a meta-analysis. , 2014, AJR. American journal of roentgenology.

[21]  Tristan Barrett,et al.  Dynamic contrast-enhanced MRI of prostate cancer at 3 T: a study of pharmacokinetic parameters. , 2007, AJR. American journal of roentgenology.

[22]  Silvia D. Chang,et al.  Combined diffusion‐weighted and dynamic contrast‐enhanced MRI for prostate cancer diagnosis—Correlation with biopsy and histopathology , 2006, Journal of magnetic resonance imaging : JMRI.

[23]  Makoto Obara,et al.  Salivary gland tumors: use of intravoxel incoherent motion MR imaging for assessment of diffusion and perfusion for the differentiation of benign from malignant tumors. , 2012, Radiology.

[24]  F. Cabitza,et al.  Unintended Consequences of Machine Learning in Medicine , 2017, JAMA.

[25]  Tao Liu,et al.  Searching for prostate cancer by fully automated magnetic resonance imaging classification: deep learning versus non-deep learning , 2017, Scientific Reports.

[26]  L. McDonald,et al.  Unintended consequences of machine learning in medicine? , 2017, F1000Research.

[27]  S. Iwata,et al.  Clustering procedures for the optimal selection of data sets from multiple crystals in macromolecular crystallography , 2012, Acta crystallographica. Section D, Biological crystallography.

[28]  Stuart A. Taylor,et al.  Zone-specific logistic regression models improve classification of prostate cancer on multi-parametric MRI , 2015, European Radiology.

[29]  Chunhong Hu,et al.  Differentiation of prostate cancer lesions in the Transition Zone by diffusion-weighted MRI , 2017, European journal of radiology open.

[30]  Xuna Zhao,et al.  Detection of prostate cancer in peripheral zone: comparison of MR diffusion tensor imaging, quantitative dynamic contrast-enhanced MRI, and the two techniques combined at 3.0 T , 2014, Acta radiologica.

[31]  D. Margolis,et al.  PI-RADS Prostate Imaging - Reporting and Data System: 2015, Version 2. , 2016, European urology.

[32]  Fionn Murtagh,et al.  Algorithms for hierarchical clustering: an overview , 2012, WIREs Data Mining Knowl. Discov..

[33]  P. Choyke,et al.  Decision support system for localizing prostate cancer based on multiparametric magnetic resonance imaging. , 2012, Medical physics.

[34]  Bram van Ginneken,et al.  A survey on deep learning in medical image analysis , 2017, Medical Image Anal..

[35]  M. Knopp,et al.  Estimating kinetic parameters from dynamic contrast‐enhanced t1‐weighted MRI of a diffusable tracer: Standardized quantities and symbols , 1999, Journal of magnetic resonance imaging : JMRI.

[36]  D. Margolis,et al.  Influence of the Location and Zone of Tumor in Prostate Cancer Detection and Localization on 3-T Multiparametric MRI Based on PI-RADS Version 2. , 2020, AJR. American journal of roentgenology.

[37]  David Atkinson,et al.  Machine learning classifiers can predict Gleason pattern 4 prostate cancer with greater accuracy than experienced radiologists , 2019, European Radiology.

[38]  Tosiaki Miyati,et al.  Triexponential function analysis of diffusion‐weighted MRI for diagnosing prostate cancer , 2016, Journal of magnetic resonance imaging : JMRI.

[39]  T. Yamasaki,et al.  Detectability of prostate cancer in different parts of the gland with 3-Tesla multiparametric magnetic resonance imaging: correlation with whole-mount histopathology , 2019, International Journal of Clinical Oncology.

[40]  Oleg S. Pianykh,et al.  Current Applications and Future Impact of Machine Learning in Radiology. , 2018, Radiology.

[41]  D. Le Bihan,et al.  Separation of diffusion and perfusion in intravoxel incoherent motion MR imaging. , 1988, Radiology.

[42]  Xiaohan Liu,et al.  Biexponential Apparent Diffusion Coefficients Values in the Prostate: Comparison among Normal Tissue, Prostate Cancer, Benign Prostatic Hyperplasia and Prostatitis , 2013, Korean journal of radiology.

[43]  J. C. Dunn,et al.  A Fuzzy Relative of the ISODATA Process and Its Use in Detecting Compact Well-Separated Clusters , 1973 .