Prostate Project

Clare Tempany Kemal Tuncali Fiona Fennessy Junichi Tokuda Andrey Fedorov
Clare M. Tempany, MD
Core Lead
Kemal Tuncali, MD
Co-Investigator
Fiona Fennessy, MD, PhD
Project Lead
Junichi Tokuda, PhD
Project Lead
Andriy Fedorov, PhD
Project Lead

There are two complex issues that drive the clinical need to change current paradigms for prostate cancer (PCa): The inability to predict aggressiveness of a given cancer, which in turn leads to over treatment, and the increasing evidence that disease progression in men with seemingly low-risk PCa is due to inadequate biopsy sampling. Recent trends indicate that the treatment of patients with localized PCa is shifting more and more towards either active surveillance or focal therapy. Technical solutions to address these challenges, and their validation in clinic, are lacking. We are working to address these challenges by integrating innovative MR image acquisition and analysis with the MR targeted biopsy platform we developed in the previous cycle. We are developing a diagnostic biomedical imaging platform to detect, characterize and diagnose prostate cancer and will provide new opportunities to understand the aggressiveness and heterogeneity of prostate cancer and ultimately allow for development and testing of new predictive markers in focal therapy. Our projects are:

Platform for validating novel imaging biomarkers with molecular and routine pathology.  We are developing methods of assessment of tumor heterogeneity by supplementing mpMRI with new hypoxia and multi b value MR imaging and add molecular profiling to the pathology options for core biopsy tissue, thus provide a unique platform for imaging, biopsy and both routine and molecular pathology. We will correlate genomic diversity with MR imaging parameters. We will propose novel motion compensation techniques combined with hypoxia imaging that will be applied jointly with the multi-b-value diffusion weighted imaging (DWI) for improved characterization of PCa. These novel-imaging approaches will be validated in biopsy and cryotherapy patient cohorts. (Contact: Clare M. Tempany, Fiona Fennessy)

Platform for focal cryoablation of PCa with accurate temperature mapping and motion compensation. Our goal is to develop and evaluate thermometry methods to monitor MR-guided focal cryoablation for localized prostate cancer, by internal ice ball thermometry using a “voxelwise thermal history” method. We will develop and test a new method for tracking the prostate gland motion, using active MR tracking coils embedded in a urethral warming catheter, investigate Ultrashort TE (UTE) MRI to monitor the internal thermal dosimetry within the ice-ball, and develop and evaluate software for voxel-wise thermal history tracking during all stages of the procedure. (Contact: Junichi Tokuda)

Informatics solution in support of targeted prostate biopsy and focal therapy for localized prostate cancer. This aim will have three tasks: 1) develop software tools to support structured PCa reporting and image registration for biopsy and focal therapy applications; 2) investigate and implement improved practices for structured data collection and provenance, prepare and disseminate curated validation datasets to facilitate validation of the role of mpMRI in cancer characterization and the evaluation of image registration accuracy/reliability; 3) investigate methods for non-rigid registration to enable recovery of prostate gland deformation for treatment response assessment and propose and apply methodologies for statistical assessment of the reliability of the registration tools. All three aims are interconnected, and leverage unique resources provided by the Center to enable development and validation of novel solutions, which will enable subsequent dissemination and application in other institutions, academic and community hospital settings. In addition to developing novel technologies, we will create platform for collecting validation imaging datasets annotated with the analysis results, molecular and pathology markers, which will be one of a kind resource for investigating the role of imaging and development of novel image analysis tools for PCa. In summary we will design, develop and test a comprehensive platform to provide a MR imaging biomarker for prostate cancer detection, characterization and provide techniques to supplement routine diagnostics with molecular profiling and generalizable image processing tools.(Contact: Andriy Fedorov)

Software and Documentation

3D Slicer, a comprehensive open source platform for medical image analysis, contains several modules that have been contributed by us for Image-Guided Prostate Interventions. These include:

Data

Presentations

These presentations have been selected as tutorials for readers interested in learning about the clinical science and technology of the Prostate Core.

Links

Full Publication List

In NIH/NLM database and in our Abstracts Database

Select Recent Publications

Glazer DI, Mayo-Smith WW, Sainani NI, Sadow CA, Vangel MG, Tempany CM, Dunne RM. Interreader Agreement of Prostate Imaging Reporting and Data System Version 2 Using an In-Bore MRI-Guided Prostate Biopsy Cohort: A Single Institution's Initial Experience. AJR Am J Roentgenol. 2017 :W1-W7.Abstract
OBJECTIVE: The purpose of this study is to determine the interobserver agreement of the Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) for diagnosing prostate cancer using in-bore MRI-guided prostate biopsy as the reference standard. MATERIALS AND METHODS: Fifty-nine patients underwent in-bore MRI-guided prostate biopsy between January 21, 2010, and August 21, 2013, and underwent diagnostic multiparametric MRI 6 months or less before biopsy. A single index lesion per patient was selected after retrospective review of MR images. Three fellowship-trained abdominal radiologists (with 1-11 years' experience) blinded to clinical information interpreted all studies according to PI-RADSv2. Interobserver agreement was assessed using Cohen kappa statistics. RESULTS: Thirty-eight lesions were in the peripheral zone and 21 were in the transition zone. Cancer was diagnosed in 26 patients (44%). Overall PI-RADS scores were higher for all biopsy-positive lesions (mean ± SD, 3.9 ± 1.1) than for biopsy-negative lesions (3.1 ± 1.0; p < 0.0001) and for clinically significant lesions (4.2 ± 1.0) than for clinically insignificant lesions (3.1 ± 1.0; p < 0.0001). Overall suspicion score interobserver agreement was moderate (κ = 0.45). There was moderate interobserver agreement among overall PI-RADS scores in the peripheral zone (κ = 0.46) and fair agreement in the transition zone (κ = 0.36). CONCLUSION: PI-RADSv2 scores were higher in the biopsy-positive group. PI-RADSv2 showed moderate interobserver agreement among abdominal radiologists with no prior experience using the scoring system.
Fedorov A, Vangel MG, Tempany CM, Fennessy FM. Multiparametric Magnetic Resonance Imaging of the Prostate: Repeatability of Volume and Apparent Diffusion Coefficient Quantification. Invest Radiol. 2017;52 (9) :538-46.Abstract
OBJECTIVES: The aim of this study was to evaluate the repeatability of a region of interest (ROI) volume and mean apparent diffusion coefficient (ADC) in standard-of-care 3 T multiparametric magnetic resonance imaging (mpMRI) of the prostate obtained with the use of endorectal coil. MATERIALS AND METHODS: This prospective study was Health Insurance Portability and Accountability Act compliant, with institutional review board approval and written informed consent. Men with confirmed or suspected treatment-naive prostate cancer scheduled for mpMRI were offered a repeat mpMRI within 2 weeks. Regions of interest corresponding to the whole prostate gland, the entire peripheral zone (PZ), normal PZ, and suspected tumor ROI (tROI) on axial T2-weighted, dynamic contrast-enhanced subtract, and ADC images were annotated and assessed using Prostate Imaging Reporting and Data System (PI-RADS) v2. Repeatability of the ROI volume for each of the analyzed image types and mean ROI ADC was summarized with repeatability coefficient (RC) and RC%. RESULTS: A total of 189 subjects were approached to participate in the study. Of 40 patients that gave initial agreement, 15 men underwent 2 mpMRI examinations and completed the study. Peripheral zone tROIs were identified in 11 subjects. Tumor ROI volume was less than 0.5 mL in 8 of 11 subjects. PI-RADS categories were identical between baseline-repeat studies in 11/15 subjects and differed by 1 point in 4/15. Peripheral zone tROI volume RC (RC%) was 233 mm (71%) on axial T2-weighted, 422 mm (112%) on ADC, and 488 mm (119%) on dynamic contrast-enhanced subtract. Apparent diffusion coefficient ROI mean RC (RC%) were 447 × 10 mm/s (42%) in PZ tROI and 471 × 10 mm/s (30%) in normal PZ. Significant difference in repeatability of the tROI volume across series was observed (P < 0.005). The mean ADC RC% was lower than volume RC% for tROI ADC (P < 0.05). CONCLUSIONS: PI-RADS v2 overall assessment was highly repeatable. Multiparametric magnetic resonance imaging sequences differ in volume measurement repeatability. The mean tROI ADC is more repeatable compared with tROI volume in ADC. Repeatability of prostate ADC is comparable with that in other abdominal organs.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
Velez E, Fedorov A, Tuncali K, Olubiyi O, Allard CB, Kibel AS, Tempany CM. Pathologic Correlation of Transperineal In-Bore 3-Tesla Magnetic Resonance Imaging-Guided Prostate Biopsy Samples with Radical Prostatectomy Specimen. Abdom Radiol (NY). 2017;42 (8) :2154-9.Abstract

PURPOSE: To determine the accuracy of in-bore transperineal 3-Tesla (T) magnetic resonance (MR) imaging-guided prostate biopsies for predicting final Gleason grades in patients who subsequently underwent radical prostatectomy (RP). METHODS: A retrospective review of men who underwent transperineal MR imaging-guided prostate biopsy (tpMRGB) with subsequent radical prostatectomy within 1 year was conducted from 2010 to 2015. All patients underwent a baseline 3-T multiparametric MRI (mpMRI) with endorectal coil and were selected for biopsy based on MR findings of a suspicious prostate lesion and high degree of clinical suspicion for cancer. Spearman correlation was performed to assess concordance between tpMRGB and final RP pathology among patients with and without previous transrectal ultrasound (TRUS)-guided biopsies. RESULTS: A total of 24 men met all eligibility requirements, with a median age of 65 years (interquartile range [IQR] 11.7). The median time from biopsy to RP was 85 days (IQR 50.5). Final pathology revealed Gleason 3 + 4 = 7 in 12 patients, 4 + 3 = 7 in 10 patients, and 4 + 4 = 8 in 2 patients. A strong correlation (ρ: +0.75, p < 0.001) between tpMRGB and RP results was observed, with Gleason scores concordant in 17 cases (71%). 16 of the 24 patients underwent prior TRUS biopsies. Subsequent tpMRGB revealed Gleason upgrading in 88% of cases, which was concordant with RP Gleason scores in 69% of cases (ρ: +0.75, p < 0.001). CONCLUSION: Final Gleason scores diagnosed by tpMRGB at 3-T correlate strongly with final RP surgical pathology. This may facilitate prostate cancer diagnosis, particularly in patients with negative or low-grade TRUS biopsy results in whom clinically significant cancer is suspected or detected on mpMRI.

Glazer DI, Hassanzadeh E, Fedorov A, Olubiyi OI, Goldberger SS, Penzkofer T, Flood TA, Masry P, Mulkern RV, Hirsch MS, et al. Diffusion-weighted Endorectal MR Imaging at 3T for Prostate Cancer: Correlation with Tumor Cell Density and Percentage Gleason Pattern on Whole Mount Pathology. Abdom Radiol (NY). 2017;42 (3) :918-25.Abstract

OBJECTIVE: To determine if tumor cell density and percentage of Gleason pattern within an outlined volumetric tumor region of interest (TROI) on whole-mount pathology (WMP) correlate with apparent diffusion coefficient (ADC) values on corresponding TROIs outlined on pre-operative MRI. METHODS: Men with biopsy-proven prostate adenocarcinoma undergoing multiparametric MRI (mpMRI) prior to prostatectomy were consented to this prospective study. WMP and mpMRI images were viewed using 3D Slicer and each TROI from WMP was contoured on the high b-value ADC maps (b0, 1400). For each TROI outlined on WMP, TCD (tumor cell density) and the percentage of Gleason pattern 3, 4, and 5 were recorded. The ADCmean, ADC10th percentile, ADC90th percentile, and ADCratio were also calculated in each case from the ADC maps using 3D Slicer. RESULTS: Nineteen patients with 21 tumors were included in this study. ADCmean values for TROIs were 944.8 ± 327.4 vs. 1329.9 ± 201.6 mm(2)/s for adjacent non-neoplastic prostate tissue (p < 0.001). ADCmean, ADC10th percentile, and ADCratio values for higher grade tumors were lower than those of lower grade tumors (mean 809.71 and 1176.34 mm(2)/s, p = 0.014; 10th percentile 613.83 and 1018.14 mm(2)/s, p = 0.009; ratio 0.60 and 0.94, p = 0.005). TCD and ADCmean (ρ = -0.61, p = 0.005) and TCD and ADC10th percentile (ρ = -0.56, p = 0.01) were negatively correlated. No correlation was observed between percentage of Gleason pattern and ADC values. CONCLUSION: DWI MRI can characterize focal prostate cancer using ADCratio, ADC10th percentile, and ADCmean, which correlate with pathological tumor cell density.

Hassanzadeh E, Glazer DI, Dunne RM, Fennessy FM, Harisinghani MG, Tempany CM. Prostate Imaging Reporting and Data System Version 2 (PI-RADS v2): A Pictorial Review. Abdom Radiol (NY). 2017;42 (1) :278-89.Abstract

The most recent edition of the prostate imaging reporting and data system (PI-RADS version 2) was developed based on expert consensus of the international working group on prostate cancer. It provides the minimum acceptable technical standards for MR image acquisition and suggests a structured method for multiparametric prostate MRI (mpMRI) reporting. T1-weighted, T2-weighted (T2W), diffusion-weighted (DWI), and dynamic contrast-enhanced (DCE) imaging are the suggested sequences to include in mpMRI. The PI-RADS version 2 scoring system enables the reader to assess and rate all focal lesions detected at mpMRI to determine the likelihood of a clinically significant cancer. According to PI-RADS v2, a lesion with a Gleason score ≥7, volume >0.5 cc, or extraprostatic extension is considered clinically significant. PI-RADS v2 uses the concept of a dominant MR sequence based on zonal location of the lesion rather than summing each component score, as was the case in version 1. The dominant sequence in the peripheral zone is DWI and the corresponding apparent diffusion coefficient (ADC) map, with a secondary role for DCE in equivocal cases (PI-RADS score 3). For lesions in the transition zone, T2W images are the dominant sequence with DWI/ADC images playing a supporting role in the case of an equivocal lesion.

Eslami S, Shang W, Li G, Patel N, Fischer GS, Tokuda J, Hata N, Tempany CM, Iordachita I. In-bore Prostate Transperineal Interventions with an MRI-guided Parallel Manipulator: System Development and Preliminary Evaluation. Int J Med Robot. 2016;12 (2) :199-213.Abstract

BACKGROUND: Robot-assisted minimally-invasive surgery is well recognized as a feasible solution for diagnosis and treatment of prostate cancer in humans. METHODS: This paper discusses the kinematics of a parallel 4 Degrees-of-Freedom (DOF) surgical manipulator designed for minimally invasive in-bore prostate percutaneous interventions through the patient's perineum. The proposed manipulator takes advantage of four sliders actuated by MRI-compatible piezoelectric motors and incremental rotary encoders. Errors, mostly originating from the design and manufacturing process, need to be identified and reduced before the robot is deployed in clinical trials. RESULTS: The manipulator has undergone several experiments to evaluate the repeatability and accuracy (about 1 mm in air (in x or y direction) at the needle's reference point) of needle placement, which is an essential concern in percutaneous prostate interventions. CONCLUSION: The acquired results endorse the sustainability, precision and reliability of the manipulator. Copyright © 2015 John Wiley & Sons, Ltd.

Penzkofer T, Tuncali K, Fedorov A, Song S-E, Tokuda J, Fennessy FM, Vangel MG, Kibel AS, Mulkern RV, Wells WM, et al. Transperineal In-Bore 3-T MR Imaging-guided Prostate Biopsy: A Prospective Clinical Observational Study. Radiology. 2015;274 (1) :170-80.Abstract

PURPOSE: To determine the detection rate, clinical relevance, Gleason grade, and location of prostate cancer ( PCa prostate cancer ) diagnosed with and the safety of an in-bore transperineal 3-T magnetic resonance (MR) imaging-guided prostate biopsy in a clinically heterogeneous patient population. MATERIALS AND METHODS: This prospective retrospectively analyzed study was HIPAA compliant and institutional review board approved, and informed consent was obtained. Eighty-seven men (mean age, 66.2 years ± 6.9) underwent multiparametric endorectal prostate MR imaging at 3 T and transperineal MR imaging-guided biopsy. Three subgroups of patients with at least one lesion suspicious for cancer were included: men with no prior PCa prostate cancer diagnosis, men with PCa prostate cancer who were undergoing active surveillance, and men with treated PCa prostate cancer and suspected recurrence. Exclusion criteria were prior prostatectomy and/or contraindication to 3-T MR imaging. The transperineal MR imaging-guided biopsy was performed in a 70-cm wide-bore 3-T device. Overall patient biopsy outcomes, cancer detection rates, Gleason grade, and location for each subgroup were evaluated and statistically compared by using χ(2) and one-way analysis of variance followed by Tukey honestly significant difference post hoc comparisons. RESULTS: Ninety biopsy procedures were performed with no serious adverse events, with a mean of 3.7 targets sampled per gland. Cancer was detected in 51 (56.7%) men: 48.1% (25 of 52) with no prior PCa prostate cancer , 61.5% (eight of 13) under active surveillance, and 72.0% (18 of 25) in whom recurrence was suspected. Gleason pattern 4 or higher was diagnosed in 78.1% (25 of 32) in the no prior PCa prostate cancer and active surveillance groups. Gleason scores were not assigned in the suspected recurrence group. MR targets located in the anterior prostate had the highest cancer yield (40 of 64, 62.5%) compared with those for the other parts of the prostate (P < .001). CONCLUSION: In-bore 3-T transperineal MR imaging-guided biopsy, with a mean of 3.7 targets per gland, allowed detection of many clinically relevant cancers, many of which were located anteriorly.

Fedorov A, Khallaghi S, Sánchez AC, Lasso A, Fels S, Tuncali K, Sugar EN, Kapur T, Zhang C, Wells III WM, et al. Open-source Image Registration for MRI-TRUS Fusion-guided Prostate Interventions. Int J Comput Assist Radiol Surg. 2015;10 (6) :925-34.Abstract

PURPOSE: We propose two software tools for non-rigid registration of MRI and transrectal ultrasound (TRUS) images of the prostate. Our ultimate goal is to develop an open-source solution to support MRI-TRUS fusion image guidance of prostate interventions, such as targeted biopsy for prostate cancer detection and focal therapy. It is widely hypothesized that image registration is an essential component in such systems. METHODS: The two non-rigid registration methods are: (1) a deformable registration of the prostate segmentation distance maps with B-spline regularization and (2) a finite element-based deformable registration of the segmentation surfaces in the presence of partial data. We evaluate the methods retrospectively using clinical patient image data collected during standard clinical procedures. Computation time and Target Registration Error (TRE) calculated at the expert-identified anatomical landmarks were used as quantitative measures for the evaluation. RESULTS: The presented image registration tools were capable of completing deformable registration computation within 5 min. Average TRE was approximately 3 mm for both methods, which is comparable with the slice thickness in our MRI data. Both tools are available under nonrestrictive open-source license. CONCLUSIONS: We release open-source tools that may be used for registration during MRI-TRUS-guided prostate interventions. Our tools implement novel registration approaches and produce acceptable registration results. We believe these tools will lower the barriers in development and deployment of interventional research solutions and facilitate comparison with similar tools.