ProsRegNet: A deep learning framework for registration of MRI and histopathology images of the prostate

Magnetic resonance imaging (MRI) is an increasingly important tool for the diagnosis and treatment of prostate cancer. However, interpretation of MRI suffers from high inter-observer variability across radiologists, thereby contributing to missed clinically significant cancers, overdiagnosed low-risk cancers, and frequent false positives. Interpretation of MRI could be greatly improved by providing radiologists with an answer key that clearly shows cancer locations on MRI. Registration of histopathology images from patients who had radical prostatectomy to pre-operative MRI allows such mapping of ground truth cancer labels onto MRI. However, traditional MRI-histopathology registration approaches are computationally expensive and require careful choices of the cost function and registration hyperparameters. This paper presents ProsRegNet, a deep learning-based pipeline to accelerate and simplify MRI-histopathology image registration in prostate cancer. Our pipeline consists of image preprocessing, estimation of affine and deformable transformations by deep neural networks, and mapping cancer labels from histopathology images onto MRI using estimated transformations. We trained our neural network using MR and histopathology images of 99 patients from our internal cohort (Cohort 1) and evaluated its performance using 53 patients from three different cohorts (an additional 12 from Cohort 1 and 41 from two public cohorts). Results show that our deep learning pipeline has achieved more accurate registration results and is at least 20 times faster than a state-of-the-art registration algorithm. This important advance will provide radiologists with highly accurate prostate MRI answer keys, thereby facilitating improvements in the detection of prostate cancer on MRI. Our code is freely available at https://github.com/pimed//ProsRegNet.

[1]  Kristy K. Brock,et al.  Biomechanical model-based deformable registration of MRI and histopathology for clinical prostatectomy , 2011, Journal of pathology informatics.

[2]  Max A. Viergever,et al.  A deep learning framework for unsupervised affine and deformable image registration , 2018, Medical Image Anal..

[3]  Orith Portnoy,et al.  Effects of "real life" prostate MRI inter-observer variability on total needle samples and indication for biopsy. , 2020, Urologic oncology.

[4]  Virginia E Rogers,et al.  Accuracy of tumor segmentation from multi-parametric prostate MRI and 18F-choline PET/CT for focal prostate cancer therapy applications , 2018, EJNMMI Research.

[5]  Shyam Natarajan,et al.  A system for evaluating magnetic resonance imaging of prostate cancer using patient-specific 3D printed molds. , 2014, American journal of clinical and experimental urology.

[6]  Xu Han,et al.  Networks for Joint Affine and Non-Parametric Image Registration , 2019, 2019 IEEE/CVF Conference on Computer Vision and Pattern Recognition (CVPR).

[7]  G. Metzger,et al.  Registration of in vivo prostate MRI and pseudo‐whole mount histology using Local Affine Transformations guided by Internal Structures (LATIS) , 2015, Journal of magnetic resonance imaging : JMRI.

[8]  Xin Yang,et al.  Automated Detection of Clinically Significant Prostate Cancer in mp-MRI Images Based on an End-to-End Deep Neural Network , 2018, IEEE Transactions on Medical Imaging.

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

[10]  Andriy Fedorov,et al.  The Role of Pathology Correlation Approach in Prostate Cancer Index Lesion Detection and Quantitative Analysis with Multiparametric MRI , 2015, Academic radiology.

[11]  Christian Kunder,et al.  Framework for the co-registration of MRI and histology images in prostate cancer patients with radical prostatectomy , 2019, Medical Imaging: Image Processing.

[12]  Baris Turkbey,et al.  Multiparametric 3T prostate magnetic resonance imaging to detect cancer: histopathological correlation using prostatectomy specimens processed in customized magnetic resonance imaging based molds. , 2011, The Journal of urology.

[13]  Mert R. Sabuncu,et al.  An Unsupervised Learning Model for Deformable Medical Image Registration , 2018, 2018 IEEE/CVF Conference on Computer Vision and Pattern Recognition.

[14]  Anant Madabhushi,et al.  Histostitcher™: An informatics software platform for reconstructing whole-mount prostate histology using the extensible imaging platform framework , 2014, Journal of pathology informatics.

[15]  Ruiming Cao,et al.  Joint Prostate Cancer Detection and Gleason Score Prediction in mp-MRI via FocalNet , 2019, IEEE Transactions on Medical Imaging.

[16]  Josef Sivic,et al.  Convolutional Neural Network Architecture for Geometric Matching , 2019, IEEE Transactions on Pattern Analysis and Machine Intelligence.

[17]  Richard E. Fan,et al.  Prostate Magnetic Resonance Imaging Interpretation Varies Substantially Across Radiologists. , 2017, European urology focus.

[18]  Nathan Lay,et al.  Prostate cancer detection from multi-institution multiparametric MRIs using deep convolutional neural networks , 2018, Journal of medical imaging.

[19]  Terry M. Peters,et al.  Registration of in-vivo to ex-vivo MRI of surgically resected specimens: A pipeline for histology to in-vivo registration , 2015, Journal of Neuroscience Methods.

[20]  Maik Stille,et al.  3D reconstruction of 2D fluorescence histology images and registration with in vivo MR images: Application in a rodent stroke model , 2013, Journal of Neuroscience Methods.

[21]  Jun Zhang,et al.  Inverse-Consistent Deep Networks for Unsupervised Deformable Image Registration , 2018, ArXiv.

[22]  Terry M. Peters,et al.  Image registration of ex-vivo MRI to sparsely sectioned histology of hippocampal and neocortical temporal lobe specimens , 2013, NeuroImage.

[23]  Hyunjin Park,et al.  Registration methodology for histological sections and in vivo imaging of human prostate. , 2008, Academic radiology.

[24]  Joseph S Koopmeiners,et al.  Detection of Prostate Cancer: Quantitative Multiparametric MR Imaging Models Developed Using Registered Correlative Histopathology. , 2016, Radiology.

[25]  Jian Sun,et al.  Deep Residual Learning for Image Recognition , 2015, 2016 IEEE Conference on Computer Vision and Pattern Recognition (CVPR).

[26]  Nilanjan Ray,et al.  Deep deformable registration: Enhancing accuracy by fully convolutional neural net , 2016, Pattern Recognit. Lett..

[27]  Anant Madabhushi,et al.  Co-registration of pre-operative CT with ex vivo surgically excised ground glass nodules to define spatial extent of invasive adenocarcinoma on in vivo imaging: a proof-of-concept study , 2017, European Radiology.

[28]  Arvid Lundervold,et al.  Intensity-based volumetric registration of magnetic resonance images and whole-mount sections of the prostate , 2017, Comput. Medical Imaging Graph..

[29]  M. Parmar,et al.  Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confi rmatory study , 2018 .

[30]  Wei Shao,et al.  Registration of presurgical MRI and histopathology images from radical prostatectomy via RAPSODI , 2020, Medical physics.

[31]  Aaron Fenster,et al.  Prostate: registration of digital histopathologic images to in vivo MR images acquired by using endorectal receive coil. , 2012, Radiology.

[32]  Marc Niethammer,et al.  Quicksilver: Fast predictive image registration – A deep learning approach , 2017, NeuroImage.

[33]  Baris Turkbey,et al.  Multiparametric MRI and prostate cancer diagnosis and risk stratification , 2012, Current opinion in urology.

[34]  Anant Madabhushi,et al.  Co-Registration of ex vivo Surgical Histopathology and in vivo T2 weighted MRI of the Prostate via multi-scale spectral embedding representation , 2017, Scientific Reports.

[35]  R. Lenkinski,et al.  Elastic registration of multimodal prostate MRI and histology via multiattribute combined mutual information. , 2011, Medical physics.

[36]  Hervé Delingette,et al.  Learning a Probabilistic Model for Diffeomorphic Registration , 2018, IEEE Transactions on Medical Imaging.

[37]  Baris Turkbey,et al.  Overview of dynamic contrast-enhanced MRI in prostate cancer diagnosis and management. , 2012, AJR. American journal of roentgenology.

[38]  Jimmy Ba,et al.  Adam: A Method for Stochastic Optimization , 2014, ICLR.

[39]  Cheng Soon Ong,et al.  Development of a registration framework to validate MRI with histology for prostate focal therapy. , 2015, Medical physics.

[40]  Mert R. Sabuncu,et al.  Unsupervised Learning for Fast Probabilistic Diffeomorphic Registration , 2018, MICCAI.

[41]  Baris Turkbey,et al.  Variability of the Positive Predictive Value of PI-RADS for Prostate MRI across 26 Centers: Experience of the Society of Abdominal Radiology Prostate Cancer Disease-focused Panel. , 2020, Radiology.

[42]  Wei Shao,et al.  Population Shape Collapse in Large Deformation Registration of MR Brain Images , 2016, 2016 IEEE Conference on Computer Vision and Pattern Recognition Workshops (CVPRW).

[43]  Mert R. Sabuncu,et al.  VoxelMorph: A Learning Framework for Deformable Medical Image Registration , 2018, IEEE Transactions on Medical Imaging.

[44]  Indrani Bhattacharya,et al.  CorrSigNet: Learning CORRelated Prostate Cancer SIGnatures from Radiology and Pathology Images for Improved Computer Aided Diagnosis , 2020, MICCAI.

[45]  Holden H. Wu,et al.  A system using patient‐specific 3D‐printed molds to spatially align in vivo MRI with ex vivo MRI and whole‐mount histopathology for prostate cancer research , 2018, Journal of magnetic resonance imaging : JMRI.