Prostate Core

C Tempany K Tuncali F Fennessy Junichi Tokuda A 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 projects are interconnected, and leverage unique resources provided by this Center. In addition to developing novel technologies, we are creating a platform for collecting validation imaging datasets annotated with the analysis results, molecular and pathology markers, to build a unique resource for investigating the role of imaging and development of novel image analysis tools for prostate cancer. (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 PubMed

 

Select Recent Publications

Pedro Moreira, Kemal Tuncali, Clare M Tempany, and Junichi Tokuda. 8/2020. “The Impact of Placement Errors on the Tumor Coverage in MRI-Guided Focal Cryoablation of Prostate Cancer.” Acad Radiol, S1076, Pp. 6332(20)30429-3.Abstract
RATIONALE AND OBJECTIVES: There have been multiple investigations defining and reporting the effectiveness of focal cryoablation as a treatment option for organ-confined prostate cancer. However, the impact of cryo-needle/probe placement accuracy within the tumor and gland has not been extensively studied. We analyzed how variations in the placement of the cryo-needles, specifically errors leading to incomplete ablation, may affect prostate cancer's resulting cryoablation. MATERIALS AND METHODS: We performed a study based on isothermal models using Monte Carlo simulations to analyze the impact of needle placement errors on tumor coverage and the probability of positive ablation margin. We modeled the placement error as a Gaussian noise on the cryo-needle position. The analysis used retrospective MRI data of 15 patients with biopsy-proven, unifocal, and MRI visible prostate cancer to calculate the impact of placement error on the volume of the tumor encompassed by the -40°C and -20°C isotherms using one to four cryo-needles. RESULTS: When the standard deviation of the placement error reached 3 mm, the tumor coverage was still above 97% with the -20°C isotherm, and above 81% with the -40°C isotherm using two cryo-needles or more. The probability of positive margin was significantly lower considering the -20°C isotherm (0.04 for three needles) than using the -40°C isotherm (0.66 for three needles). CONCLUSION: The results indicated that accurate cryo-needle placement is essential for the success of focal cryoablation of prostate cancer. The analysis shows that an admissible targeting error depends on the lethal temperature considered and the number of cryo-needles used.
Aida Steiner, Gabriela Alban, Teresa Cheng, Tina Kapur, Camden Bay, Pierre-Yves McLaughlin, Martin King, Clare Tempany, and Larissa J Lee. 4/2020. “Vaginal Recurrence of Endometrial Cancer: MRI Characteristics and Correlation With Patient Outcome After Salvage Radiation Therapy.” Abdom Radiol (NY), 45, 4, Pp. 1122-31.Abstract
PURPOSE: To evaluate MRI characteristics in vaginal recurrence of endometrial cancer (EC) including tumor volume shrinkage during salvage radiotherapy, and to identify imaging features associated with survival. METHODS: Patients with vaginal recurrence of EC treated with external beam radiotherapy (EBRT) followed by brachytherapy (BT), and with available pelvic MRI at two time points: baseline and/or before BT were retrospectively identified from 2004 to 2017. MRI features including recurrence location and tissue characteristics on T2- and T1-weighted images were evaluated at baseline only. Tumor volumes were measured both at baseline and pre-BT. Survival rates and associations were evaluated by Cox regression and Fisher's exact test, respectively. RESULTS: Sixty-two patients with 36 baseline and 50 pre-BT pelvic MRIs were included (24/62 with both MRIs). Vaginal recurrence of EC was most commonly located in the vaginal apex (27/36, 75%). Tumors with a post-contrast enhancing peripheral rim or low T2 signal rim at baseline showed longer recurrence-free survival (RFS) (HR 0.2, 95% CI 0.1-0.9, P < 0.05 adjusted for histology; HR 0.2, 95% CI 0.1-0.8, P < 0.05, respectively). The median tumor shrinkage at pre-BT was 69% (range 1-99%). Neither absolute tumor volumes nor volume regression at pre-BT were associated with RFS. Lymphovascular space invasion (LVSI) at hysterectomy and adjuvant RT were associated with recurrence involving the distal vagina (both P < 0.05). CONCLUSION: Vaginal recurrences with rim enhancement at baseline MRI predicted improved RFS, while tumor volume shrinkage at pre-BT did not. Distal vaginal recurrence was more common in patients with LVSI and adjuvant RT at EC diagnosis.
Fiona M Fennessy, Andriy Fedorov, Mark G Vangel, Robert V. Mulkern, Maria Tretiakova, Rosina T Lis, Clare Tempany, and Mary-Ellen Taplin. 10/2020. “Multiparametric MRI as a Biomarker of Response to Neoadjuvant Therapy for Localized Prostate Cancer-A Pilot Study.” Acad Radiol, 27, 10, Pp. 1432-9.Abstract
RATIONALE AND OBJECTIVES: To explore a role for multiparametric MRI (mpMRI) as a biomarker of response to neoadjuvant androgen deprivation therapy (ADT) for prostate cancer (PCa). MATERIALS AND METHODS: This prospective study was approved by the institutional review board and was HIPAA compliant. Eight patients with localized PCa had a baseline mpMRI, repeated after 6-months of ADT, followed by prostatectomy. mpMRI indices were extracted from tumor and normal regions of interest (TROI/NROI). Residual cancer burden (RCB) was measured on mpMRI and on the prostatectomy specimen. Paired t-tests compared TROI/NROI mpMRI indices and pre/post-treatment TROI mpMRI indices. Spearman's rank tested for correlations between MRI/pathology-based RCB, and between pathological RCB and mpMRI indices. RESULTS: At baseline, TROI apparent diffusion coefficient (ADC) was lower and dynamic contrast enhanced (DCE) metrics were higher, compared to NROI (ADC: 806 ± 137 × 10 vs. 1277 ± 213 × 10 mm/sec, p = 0.0005; K: 0.346 ± 0.16 vs. 0.144 ± 0.06 min, p = 0.002; AUC: 0.213 ± 0.08 vs. 0.11 ± 0.03, p = 0.002). Post-treatment, there was no change in TROI ADC, but a decrease in TROI K (0.346 ± 0.16 to 0.188 ± 0.08 min; p = 0.02) and AUC (0.213 ± 0.08 to 0.13 ± 0.06; p = 0.02). Tumor volume decreased with ADT. There was no difference between mpMRI-based and pathology-based RCB, which positively correlated (⍴ = 0.74-0.81, p < 0.05). Pathology-based RCB positively correlated with post-treatment DCE metrics (⍴ = 0.76-0.70, p < 0.05) and negatively with ADC (⍴ = -0.79, p = 0.03). CONCLUSION: Given the heterogeneity of PCa, an individualized approach to ADT may maximize potential benefit. This pilot study suggests that mpMRI may serve as a biomarker of ADT response and as a surrogate for RCB at prostatectomy.
Junichi Tokuda, Qun Wang, Kemal Tuncali, Ravi T Seethamraju, Clare M Tempany, and Ehud J Schmidt. 5/2020. “Temperature-Sensitive Frozen-Tissue Imaging for Cryoablation Monitoring Using STIR-UTE MRI.” Invest Radiol, 55, 5, Pp. 310-7.Abstract
PURPOSE: The aim of this study was to develop a method to delineate the lethally frozen-tissue region (temperature less than -40°C) arising from interventional cryoablation procedures using a short tau inversion-recovery ultrashort echo-time (STIR-UTE) magnetic resonance (MR) imaging sequence. This method could serve as an intraprocedural validation of the completion of tumor ablation, reducing the number of local recurrences after cryoablation procedures. MATERIALS AND METHODS: The method relies on the short T1 and T2* relaxation times of frozen soft tissue. Pointwise Encoding Time with Radial Acquisition, a 3-dimensional UTE sequence with TE = 70 microseconds, was optimized with STIR to null tissues with a T1 of approximately 271 milliseconds, the threshold T1. Because the T1 relaxation time of frozen tissue in the temperature range of -40°C < temperature < -8°C is shorter than the threshold T1 at the 3-tesla magnetic field, tissues in this range should appear hyperintense. The sequence was evaluated in ex vivo frozen tissue, where image intensity and actual tissue temperatures, measured by thermocouples, were correlated. Thereafter, the sequence was evaluated clinically in 12 MR-guided prostate cancer cryoablations, where MR-compatible cryoprobes were used to destroy cancerous tissue and preserve surrounding normal tissue. RESULTS: The ex vivo experiment using a bovine muscle demonstrated that STIR-UTE images showed regions approximately between -40°C and -8°C as hyperintense, with tissues at lower and higher temperatures appearing dark, making it possible to identify the region likely to be above the lethal temperature inside the frozen tissue. In the clinical cases, the STIR-UTE images showed a dark volume centered on the cryoprobe shaft, Vinner, where the temperature is likely below -40°C, surrounded by a doughnut-shaped hyperintense volume, where the temperature is likely between -40°C and -8°C. The hyperintense region was itself surrounded by a dark volume, where the temperature is likely above -8°C, permitting calculation of Vouter. The STIR-UTE frozen-tissue volumes, Vinner and Vouter, appeared significantly smaller than signal voids on turbo spin echo images (P < 1.0 × 10), which are currently used to quantify the frozen-tissue volume ("the iceball"). The ratios of the Vinner and Vouter volumes to the iceball were 0.92 ± 0.08 and 0.29 ± 0.07, respectively. In a single postablation follow-up case, a strong correlation was seen between Vinner and the necrotic volume. CONCLUSIONS: Short tau inversion-recovery ultrashort echo-time MR imaging successfully delineated the area approximately between -40°C and -8°C isotherms in the frozen tissue, demonstrating its potential to monitor the lethal ablation volume during MR-guided cryoablation.
Christian Herz, Kyle MacNeil, Peter A Behringer, Junichi Tokuda, Alireza Mehrtash, Parvin Mousavi, Ron Kikinis, Fiona M Fennessy, Clare M Tempany, Kemal Tuncali, and Andriy Fedorov. 2/2020. “Open Source Platform for Transperineal In-Bore MRI-Guided Targeted Prostate Biopsy.” IEEE Trans Biomed Eng, 67, 2, Pp. 565-76.Abstract
OBJECTIVE: Accurate biopsy sampling of the suspected lesions is critical for the diagnosis and clinical management of prostate cancer. Transperineal in-bore MRI-guided prostate biopsy (tpMRgBx) is a targeted biopsy technique that was shown to be safe, efficient, and accurate. Our goal was to develop an open source software platform to support evaluation, refinement, and translation of this biopsy approach. METHODS: We developed SliceTracker, a 3D Slicer extension to support tpMRgBx. We followed modular design of the implementation to enable customization of the interface and interchange of image segmentation and registration components to assess their effect on the processing time, precision, and accuracy of the biopsy needle placement. The platform and supporting documentation were developed to enable the use of software by an operator with minimal technical training to facilitate translation. Retrospective evaluation studied registration accuracy, effect of the prostate segmentation approach, and re-identification time of biopsy targets. Prospective evaluation focused on the total procedure time and biopsy targeting error (BTE). RESULTS: Evaluation utilized data from 73 retrospective and ten prospective tpMRgBx cases. Mean landmark registration error for retrospective evaluation was 1.88 ± 2.63 mm, and was not sensitive to the approach used for prostate gland segmentation. Prospectively, we observed target re-identification time of 4.60 ± 2.40 min and BTE of 2.40 ± 0.98 mm. CONCLUSION: SliceTracker is modular and extensible open source platform for supporting image processing aspects of the tpMRgBx procedure. It has been successfully utilized to support clinical research procedures at our site.
Ananya Panda, Verena C Obmann, Wei-Ching Lo, Seunghee Margevicius, Yun Jiang, Mark Schluchter, Indravadan J Patel, Dean Nakamoto, Chaitra Badve, Mark A Griswold, Irina Jaeger, Lee E Ponsky, and Vikas Gulani. 9/2019. “MR Fingerprinting and ADC Mapping for Characterization of Lesions in the Transition Zone of the Prostate Gland.” Radiology, 292, 3, Pp. 685-94.Abstract
BackgroundPreliminary studies have shown that MR fingerprinting-based relaxometry combined with apparent diffusion coefficient (ADC) mapping can be used to differentiate normal peripheral zone from prostate cancer and prostatitis. The utility of relaxometry and ADC mapping for the transition zone (TZ) is unknown.PurposeTo evaluate the utility of MR fingerprinting combined with ADC mapping for characterizing TZ lesions.Materials and MethodsTZ lesions that were suspicious for cancer in men who underwent MRI with T2-weighted imaging and ADC mapping ( values, 50-1400 sec/mm), MR fingerprinting with steady-state free precession, and targeted biopsy (60 in-gantry and 15 cognitive targeting) between September 2014 and August 2018 in a single university hospital were retrospectively analyzed. Two radiologists blinded to Prostate Imaging Reporting and Data System (PI-RADS) scores and pathologic diagnosis drew regions of interest on cancer-suspicious lesions and contralateral visually normal TZs (NTZs) on MR fingerprinting and ADC maps. Linear mixed models compared two-reader means of T1, T2, and ADC. Generalized estimating equations logistic regression analysis was used to evaluate both MR fingerprinting and ADC in differentiating NTZ, cancers and noncancers, clinically significant (Gleason score ≥ 7) cancers from clinically insignificant lesions (noncancers and Gleason 6 cancers), and characterizing PI-RADS version 2 category 3 lesions.ResultsIn 67 men (mean age, 66 years ± 8 [standard deviation]) with 75 lesions, targeted biopsy revealed 37 cancers (six PI-RADS category 3 cancers and 31 PI-RADS category 4 or 5 cancers) and 38 noncancers (31 PI-RADS category 3 lesions and seven PI-RADS category 4 or 5 lesions). The T1, T2, and ADC of NTZ (1800 msec ± 150, 65 msec ± 22, and [1.13 ± 0.19] × 10 mm/sec, respectively) were higher than those in cancers (1450 msec ± 110, 36 msec ± 11, and [0.57 ± 0.13] × 10 mm/sec, respectively; < .001 for all). The T1, T2, and ADC in cancers were lower than those in noncancers (1620 msec ± 120, 47 msec ± 16, and [0.82 ± 0.13] × 10 mm/sec, respectively; = .001 for T1 and ADC and = .03 for T2). The area under the receiver operating characteristic curve (AUC) for T1 plus ADC was 0.94 for separation. T1 and ADC in clinically significant cancers (1440 msec ± 140 and [0.58 ± 0.14] × 10 mm/sec, respectively) were lower than those in clinically insignificant lesions (1580 msec ± 120 and [0.75 ± 0.17] × 10 mm/sec, respectively; = .001 for all). The AUC for T1 plus ADC was 0.81 for separation. Within PI-RADS category 3 lesions, T1 and ADC of cancers (1430 msec ± 220 and [0.60 ± 0.17] × 10 mm/sec, respectively) were lower than those of noncancers (1630 msec ± 120 and [0.81 ± 0.13] × 10 mm/sec, respectively; = .006 for T1 and = .004 for ADC). The AUC for T1 was 0.79 for differentiating category 3 lesions.ConclusionMR fingerprinting-based relaxometry combined with apparent diffusion coefficient mapping may improve transition zone lesion characterization.© RSNA, 2019
Martin T King, Paul L Nguyen, Ninjin Boldbaatar, David D Yang, Vinayak Muralidhar, Clare M Tempany, Robert A Cormack, Mark D Hurwitz, Warren W Suh, Mark M Pomerantz, Anthony V D'Amico, and Peter F Orio. 3/2019. “Evaluating the Influence of Prostate-specific Antigen Kinetics on Metastasis in Men with PSA Recurrence after Partial Gland Therapy.” Brachytherapy, 18, 2, Pp. 198-203.Abstract
PURPOSE: Although current Delphi Consensus guidelines do not recommend a specific definition of biochemical recurrence after partial gland therapy, these guidelines acknowledge that serial prostate-specific antigen (PSA) tests remain the best marker for monitoring disease after treatment. The purpose of this study was to determine whether PSA velocity at failure per the Phoenix (nadir + 2 ng/mL) definition is associated with metastasis and prostate cancer-specific mortality (PCSM) in a cohort of patients who experienced PSA failure after partial gland therapy. METHODS: Between 1997 and 2007, 285 patients with favorable risk prostate cancer underwent partial prostate brachytherapy to the peripheral zone. PSA velocity was calculated for 94 patients who experienced PSA failure per the Phoenix (nadir + 2) definition. Fine and Gray competing risks regression was performed to determine whether PSA velocity and other clinical factors were associated with metastasis and PCSM. RESULTS: The median time to PSA failure was 4.2 years (interquartile range: 2.2, 7.9), and the median followup time after PSA failure was 6.5 years (3.5-9.7). Seventeen patients developed metastases, and five experienced PCSM. On multivariate analysis, PSA velocity ≥3.0 ng/mL/year (adjusted hazard ratio 5.97; [2.57, 13.90]; p < 0.001) and PSA nadir (adjusted hazard ratio 0.39; [0.24, 0.64]; p < 0.001) were significantly associated with metastasis. PSA velocity ≥3.0 ng/mL/year was also associated with PCSM (HR 15.3; [1.8, 128.0]; p = 0.012) on univariate analysis. CONCLUSIONS: Rapid PSA velocity at PSA failure after partial gland treatment may be prognostic for long-term outcomes.
Wei Huang, Yiyi Chen, Andriy Fedorov, Xia Li, Guido H Jajamovich, Dariya I Malyarenko, Madhava P Aryal, Peter S LaViolette, Matthew J Oborski, Finbarr O'Sullivan, Richard G Abramson, Kourosh Jafari-Khouzani, Aneela Afzal, Alina Tudorica, Brendan Moloney, Sandeep N Gupta, Cecilia Besa, Jayashree Kalpathy-Cramer, James M Mountz, Charles M Laymon, Mark Muzi, Paul E Kinahan, Kathleen Schmainda, Yue Cao, Thomas L Chenevert, Bachir Taouli, Thomas E Yankeelov, Fiona Fennessy, and Xin Li. 3/2019. “The Impact of Arterial Input Function Determination Variations on Prostate Dynamic Contrast-Enhanced Magnetic Resonance Imaging Pharmacokinetic Modeling: A Multicenter Data Analysis Challenge, Part II.” Tomography, 5, 1, Pp. 99-109.Abstract
This multicenter study evaluated the effect of variations in arterial input function (AIF) determination on pharmacokinetic (PK) analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data using the shutter-speed model (SSM). Data acquired from eleven prostate cancer patients were shared among nine centers. Each center used a site-specific method to measure the individual AIF from each data set and submitted the results to the managing center. These AIFs, their reference tissue-adjusted variants, and a literature population-averaged AIF, were used by the managing center to perform SSM PK analysis to estimate K (volume transfer rate constant), v (extravascular, extracellular volume fraction), k (efflux rate constant), and τ (mean intracellular water lifetime). All other variables, including the definition of the tumor region of interest and precontrast T values, were kept the same to evaluate parameter variations caused by variations in only the AIF. Considerable PK parameter variations were observed with within-subject coefficient of variation (wCV) values of 0.58, 0.27, 0.42, and 0.24 for K, v, k, and τ, respectively, using the unadjusted AIFs. Use of the reference tissue-adjusted AIFs reduced variations in K and v (wCV = 0.50 and 0.10, respectively), but had smaller effects on k and τ (wCV = 0.39 and 0.22, respectively). k is less sensitive to AIF variation than K, suggesting it may be a more robust imaging biomarker of prostate microvasculature. With low sensitivity to AIF uncertainty, the SSM-unique τ parameter may have advantages over the conventional PK parameters in a longitudinal study.
Wenya Linda Bi, Ahmed Hosny, Matthew B Schabath, Maryellen L Giger, Nicolai J Birkbak, Alireza Mehrtash, Tavis Allison, Omar Arnaout, Christopher Abbosh, Ian F Dunn, Raymond H Mak, Rulla M Tamimi, Clare M Tempany, Charles Swanton, Udo Hoffmann, Lawrence H Schwartz, Robert J Gillies, Raymond Y Huang, and Hugo JWL Aerts. 3/2019. “Artificial Intelligence in Cancer Imaging: Clinical Challenges and Applications.” CA Cancer J Clin, 69, 2, Pp. 127-57.Abstract
Judgement, as one of the core tenets of medicine, relies upon the integration of multilayered data with nuanced decision making. Cancer offers a unique context for medical decisions given not only its variegated forms with evolution of disease but also the need to take into account the individual condition of patients, their ability to receive treatment, and their responses to treatment. Challenges remain in the accurate detection, characterization, and monitoring of cancers despite improved technologies. Radiographic assessment of disease most commonly relies upon visual evaluations, the interpretations of which may be augmented by advanced computational analyses. In particular, artificial intelligence (AI) promises to make great strides in the qualitative interpretation of cancer imaging by expert clinicians, including volumetric delineation of tumors over time, extrapolation of the tumor genotype and biological course from its radiographic phenotype, prediction of clinical outcome, and assessment of the impact of disease and treatment on adjacent organs. AI may automate processes in the initial interpretation of images and shift the clinical workflow of radiographic detection, management decisions on whether or not to administer an intervention, and subsequent observation to a yet to be envisioned paradigm. Here, the authors review the current state of AI as applied to medical imaging of cancer and describe advances in 4 tumor types (lung, brain, breast, and prostate) to illustrate how common clinical problems are being addressed. Although most studies evaluating AI applications in oncology to date have not been vigorously validated for reproducibility and generalizability, the results do highlight increasingly concerted efforts in pushing AI technology to clinical use and to impact future directions in cancer care.
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