Principal Investigator

Corey Wells
Arnold
Awardee Organization

University Of California Los Angeles
United States

Fiscal Year
2019
Activity Code
R21
Project End Date

Predicting the Presence of Clinically Significant Prostate Cancer using Multiparametric MRI and MR-US Fusion Biopsy

Prostate cancer is the second leading cause of cancer death in American men, accounting for 26% of new cancer diagnoses and 9% of cancer deaths in men. Active surveillance, radical prostatectomy and radiotherapy are commonly used treatments for clinically localized prostate cancer. However, current risk stratification methods cannot be used effectively to avoid subjecting patients with clinically indolent cancers to unnecessary interventions, causing significant morbidity and cost. The primary components currently involved in screening are the digital rectal exam (DRE) and serum biomarkers, such as PSA, PCA3, PHI, and 4Kscore. Unfortunately, despite advances in these tests, overdiagnosis remains a major problem due to limited specificity. As a result, 90% of patients diagnosed with prostate cancer receive treatment, even though up to 60% of those patients could be candidates for active surveillance. Such treatment often results in long-term reductions in functional outcomes. The research objective of this R21 is to develop novel techniques using multiparametric magnetic resonance imaging (mp-MRI) and MRI-ultrasound (US) fusion guided biopsy data that provide discriminatory power in distinguishing indolent versus clinically significant prostatic adenocarcinoma based on non-invasive imaging. We propose to implement a multi-instance learning (MIL) based convolutional neural network (CNN) model for clinical prostate mp-MRI sequences to generate new quantitative imaging features representative of the underlying tissue. Our MIL-CNN model will accommodate ground truth labels from pathology whole mount specimens, as well as MRI-US fusion biopsy results. Hierarchical CNN features will be used to predict voxellevel cancer suspicion, thereby enabling a novel method for performing “imaging biopsy.” Finally, voxel-level suspicion maps will be aggregated into patient-level quantitative imaging biomarkers and combined with clinical data to create a multimodal nomogram for performing risk stratification.

Publications

  • Li W, Li J, Sarma KV, Ho KC, Shen S, Knudsen BS, Gertych A, Arnold CW. Path R-CNN for Prostate Cancer Diagnosis and Gleason Grading of Histological Images. IEEE transactions on medical imaging. 2019 Apr;38(4):945-954. Epub 2018 Oct 12. PMID: 30334752
  • Raman AG, Sarma KV, Raman SS, Priester AM, Mirak SA, Riskin-Jones HH, Dhinagar N, Speier W, Felker E, Sisk AE, Lu D, Kinnaird A, Reiter RE, Marks LS, Arnold CW. Optimizing Spatial Biopsy Sampling for the Detection of Prostate Cancer. The Journal of urology. 2021 Sep;206(3):595-603. Epub 2021 Apr 28. PMID: 33908801
  • Li W, Li J, Wang Z, Polson J, Sisk AE, Sajed DP, Speier W, Arnold CW. PathAL: An Active Learning Framework for Histopathology Image Analysis. IEEE transactions on medical imaging. 2022 May;41(5):1176-1187. Epub 2022 May 2. PMID: 34898432
  • Rajagopal A, Redekop E, Kemisetti A, Kulkarni R, Raman S, Sarma K, Magudia K, Arnold CW, Larson PEZ. Federated Learning with Research Prototypes: Application to Multi-Center MRI-based Detection of Prostate Cancer with Diverse Histopathology. Academic radiology. 2023 Apr;30(4):644-657. Epub 2023 Mar 12. PMID: 36914501
  • Dhinagar NJ, Speier W, Sarma KV, Raman A, Kinnaird A, Raman SS, Marks LS, Arnold CW. Semi-automated PIRADS scoring via mpMRI analysis. Journal of medical imaging (Bellingham, Wash.). 2020 Nov;7(6):064501. Epub 2020 Dec 29. PMID: 33392358
  • Sarma KV, Harmon S, Sanford T, Roth HR, Xu Z, Tetreault J, Xu D, Flores MG, Raman AG, Kulkarni R, Wood BJ, Choyke PL, Priester AM, Marks LS, Raman SS, Enzmann D, Turkbey B, Speier W, Arnold CW. Federated learning improves site performance in multicenter deep learning without data sharing. Journal of the American Medical Informatics Association : JAMIA. 2021 Jun 12;28(6):1259-1264. PMID: 33537772
  • Sarma KV, Raman AG, Dhinagar NJ, Priester AM, Harmon S, Sanford T, Mehralivand S, Turkbey B, Marks LS, Raman SS, Speier W, Arnold CW. Harnessing clinical annotations to improve deep learning performance in prostate segmentation. PloS one. 2021 Jun 25;16(6):e0253829. doi: 10.1371/journal.pone.0253829. eCollection 2021. PMID: 34170972
  • Li J, Speier W, Ho KC, Sarma KV, Gertych A, Knudsen BS, Arnold CW. An EM-based semi-supervised deep learning approach for semantic segmentation of histopathological images from radical prostatectomies. Computerized medical imaging and graphics : the official journal of the Computerized Medical Imaging Society. 2018 Nov;69:125-133. Epub 2018 Sep 3. PMID: 30243216
  • Li J, Li W, Sisk A, Ye H, Wallace WD, Speier W, Arnold CW. A multi-resolution model for histopathology image classification and localization with multiple instance learning. Computers in biology and medicine. 2021 Apr;131:104253. Epub 2021 Feb 10. PMID: 33601084