Prostate Research Publications

2019
Huang W, Chen Y, Fedorov A, Li X, Jajamovich GH, Malyarenko DI, Aryal MP, LaViolette PS, Oborski MJ, O'Sullivan F, et al. 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. 2019;5 (1) :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.
Bi WL, Hosny A, Schabath MB, Giger ML, Birkbak NJ, Mehrtash A, Allison T, Arnaout O, Abbosh C, Dunn IF, et al. Artificial Intelligence in Cancer Imaging: Clinical Challenges and Applications. CA Cancer J Clin. 2019;69 (2) :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.
Randall EC, Zadra G, Chetta P, Lopez BGC, Syamala S, Basu SS, Agar JN, Loda M, Tempany CM, Fennessy FM, et al. Molecular Characterization of Prostate Cancer with Associated Gleason Score using Mass Spectrometry Imaging. Mol Cancer Res. 2019;17 (5) :1155-65.Abstract
Diagnosis of prostate cancer is based on histological evaluation of tumor architecture using a system known as the 'Gleason score'. This diagnostic paradigm, while the standard of care, is time-consuming, shows intra-observer variability and provides no information about the altered metabolic pathways, which result in altered tissue architecture. Characterization of the molecular composition of prostate cancer and how it changes with respect to the Gleason score (GS) could enable a more objective and faster diagnosis. It may also aid in our understanding of disease onset and progression. In this work, we present mass spectrometry imaging for identification and mapping of lipids and metabolites in prostate tissue from patients with known prostate cancer with GS from 6 to 9. A gradient of changes in the intensity of various lipids was observed, which correlated with increasing GS. Interestingly, these changes were identified in both regions of high tumor cell density, and in regions of tissue that appeared histologically benign, possibly suggestive of pre-cancerous metabolomic changes. A total of 31 lipids, including several phosphatidylcholines, phosphatidic acids, phosphatidylserines, phosphatidylinositols and cardiolipins were detected with higher intensity in GS (4+3) compared with GS (3+4), suggesting they may be markers of prostate cancer aggression. Results obtained through mass spectrometry imaging studies were subsequently correlated with a fast, ambient mass spectrometry method for potential use as a clinical tool to support image-guided prostate biopsy. Implications: In this study we suggest that metabolomic differences between prostate cancers with different Gleason scores can be detected by mass spectrometry imaging.
Ciris PA, Chiou J-yuan G, Glazer DI, Chao T-C, Tempany-Afdhal CM, Madore B, Maier SE. Accelerated Segmented Diffusion-Weighted Prostate Imaging for Higher Resolution, Higher Geometric Fidelity, and Multi-b Perfusion Estimation. Invest Radiol. 2019;54 (4) :238-46.Abstract
PURPOSE: The aim of this study was to improve the geometric fidelity and spatial resolution of multi-b diffusion-weighted magnetic resonance imaging of the prostate. MATERIALS AND METHODS: An accelerated segmented diffusion imaging sequence was developed and evaluated in 25 patients undergoing multiparametric magnetic resonance imaging examinations of the prostate. A reduced field of view was acquired using an endorectal coil. The number of sampled diffusion weightings, or b-factors, was increased to allow estimation of tissue perfusion based on the intravoxel incoherent motion (IVIM) model. Apparent diffusion coefficients measured with the proposed segmented method were compared with those obtained with conventional single-shot echo-planar imaging (EPI). RESULTS: Compared with single-shot EPI, the segmented method resulted in faster acquisition with 2-fold improvement in spatial resolution and a greater than 3-fold improvement in geometric fidelity. Apparent diffusion coefficient values measured with the novel sequence demonstrated excellent agreement with those obtained from the conventional scan (R = 0.91 for bmax = 500 s/mm and R = 0.89 for bmax = 1400 s/mm). The IVIM perfusion fraction was 4.0% ± 2.7% for normal peripheral zone, 6.6% ± 3.6% for normal transition zone, and 4.4% ± 2.9% for suspected tumor lesions. CONCLUSIONS: The proposed accelerated segmented prostate diffusion imaging sequence achieved improvements in both spatial resolution and geometric fidelity, along with concurrent quantification of IVIM perfusion.
Peled S, Vangel M, Kikinis R, Tempany CM, Fennessy FM, Fedorov A. Selection of Fitting Model and Arterial Input Function for Repeatability in Dynamic Contrast-Enhanced Prostate MRI. Acad Radiol. 2019;26 (9) :e241-e251.Abstract
RATIONALE AND OBJECTIVES: Analysis of dynamic contrast-enhanced (DCE) magnetic resonance imaging is notable for the variability of calculated parameters. The purpose of this study was to evaluate the level of measurement variability and error/variability due to modeling in DCE magnetic resonance imaging parameters. MATERIALS AND METHODS: Two prostate DCE scans were performed on 11 treatment-naïve patients with suspected or confirmed prostate peripheral zone cancer within an interval of less than two weeks. Tumor-suspicious and normal-appearing regions of interest (ROI) in the prostate peripheral zone were segmented. Different Tofts-Kety based models and different arterial input functions, with and without bolus arrival time (BAT) correction, were used to extract pharmacokinetic parameters. The percent repeatability coefficient (%RC) of fitted model parameters K, v, and k was calculated. Paired t-tests comparing parameters in tumor-suspicious ROIs and in normal-appearing tissue evaluated each parameter's sensitivity to pathology. RESULTS: Although goodness-of-fit criteria favored the four-parameter extended Tofts-Kety model with the BAT correction included, the simplest two-parameter Tofts-Kety model overall yielded the best repeatability scores. The best %RC in the tumor-suspicious ROI was 63% for k, 28% for v and 83% for K . The best p values for discrimination between tissues were p <10 for k and K, and p = 0.11 for v. Addition of the BAT correction to the models did not improve repeatability. CONCLUSION: The parameter k, using an arterial input functions directly measured from blood signals, was more repeatable than K. Both K and k values were highly discriminatory between healthy and diseased tissues in all cases. The parameter v had high repeatability but could not distinguish the two tissue types.
Mehrtash A, Ghafoorian M, Pernelle G, Ziaei A, Heslinga FG, Tuncali K, Fedorov A, Kikinis R, Tempany CM, Wells WM, et al. Automatic Needle Segmentation and Localization in MRI with 3D Convolutional Neural Networks: Application to MRI-targeted Prostate Biopsy. IEEE Trans Med Imaging. 2019;38 (4) :1026-36.Abstract
Image-guidance improves tissue sampling during biopsy by allowing the physician to visualize the tip and trajectory of the biopsy needle relative to the target in MRI, CT, ultrasound, or other relevant imagery. This paper reports a system for fast automatic needle tip and trajectory localization and visualization in MRI that has been developed and tested in the context of an active clinical research program in prostate biopsy. To the best of our knowledge, this is the first reported system for this clinical application, and also the first reported system that leverages deep neural networks for segmentation and localization of needles in MRI across biomedical applications. Needle tip and trajectory were annotated on 583 T2-weighted intra-procedural MRI scans acquired after needle insertion for 71 patients who underwent transperenial MRI-targeted biopsy procedure at our institution. The images were divided into two independent training-validation and test sets at the patient level. A deep 3-dimensional fully convolutional neural network model was developed, trained and deployed on these samples. The accuracy of the proposed method, as tested on previously unseen data, was 2.80 mm average in needle tip detection, and 0.98° in needle trajectory angle. An observer study was designed in which independent annotations by a second observer, blinded to the original observer, were compared to the output of the proposed method. The resultant error was comparable to the measured inter-observer concordance, reinforcing the clinical acceptability of the proposed method. The proposed system has the potential for deployment in clinical routine.
Taghipour M, Ziaei A, Alessandrino F, Hassanzadeh E, Harisinghani M, Vangel M, Tempany CM, Fennessy FM. Investigating the Role of DCE-MRI, over T2 and DWI, in accurate PI-RADS v2 Assessment of Clinically Significant Peripheral Zone Prostate Lesions as Defined at Radical Prostatectomy. Abdom Radiol (NY). 2019;44 (4) :1520-7.Abstract
PURPOSE: PI-RADS v2 dictates that dynamic contrast-enhanced (DCE) imaging be used to further classify peripheral zone (PZ) cases that receive a diffusion-weighted imaging equivocal score of three (DWI3), a positive DCE resulting in an increase in overall assessment score to a four, indicative of clinically significant prostate cancer (csPCa). However, the accuracy of DCE in predicting csPCa in DWI3 PZ cases is unknown. This study sought to determine the frequency with which DCE changes the PI-RADS v2 DWI3 assessment category, and to determine the overall accuracy of DCE-MRI in equivocal PZ DWI3 lesions. MATERIALS AND METHODS: This is a retrospective study of patients with pathologically proven PCa who underwent prostate mpMRI at 3T and subsequent radical prostatectomy. PI-RADS v2 assessment categories were determined by a radiologist, aware of a diagnosis of PCa, but blinded to final pathology. csPCa was defined as a Gleason score ≥ 7 or extra prostatic extension at pathology review. Performance characteristics and diagnostic accuracy of DCE in assigning a csPCa assessment in PZ lesions were calculated. RESULTS: A total of 271 men with mean age of 59 ± 6 years mean PSA 6.7 ng/mL were included. csPCa was found in 212/271 (78.2%) cases at pathology, 209 of which were localized in the PZ. DCE was necessary to further classify (45/209) of patients who received a score of DWI3. DCE was positive in 29/45 cases, increasing the final PI-RADS v2 assessment category to a category 4, with 16/45 having a negative DCE. When compared with final pathology, DCE was correct in increasing the assessment category in 68.9% ± 7% (31/45) of DWI3 cases. CONCLUSION: DCE increases the accuracy of detection of csPCa in the majority of PZ lesions that receive an equivocal PI-RADS v2 assessment category using DWI.
deSouza NM, Tempany CM. A Risk-based Approach to Identifying Oligometastatic Disease on Imaging. Int J Cancer. 2019;144 (3) :422-30.Abstract
Recognition of <3 metastases in <2 organs, particularly in cancers with a known predisposition to oligometastatic disease (OMD) (colorectal, prostate, renal, sarcoma and lung), offers the opportunity to focally treat the lesions identified and confers a survival advantage. The reliability with which OMD is identified depends on the sensitivity of the imaging technique used for detection and may be predicted from phenotypic and genetic factors of the primary tumour, which determine metastatic risk. Whole-body or organ-specific imaging to identify oligometastases requires optimization to achieve maximal sensitivity. Metastatic lesions at multiple locations may require a variety of imaging modalities for best visualisation because the optimal image contrast is determined by tumour biology. Newer imaging techniques used for this purpose require validation. Additionally, rationalisation of imaging strategies is needed, particularly with regard to timing of imaging and follow-up studies. This article reviews the current evidence for the use of imaging for recognising OMD and proposes a risk-based roadmap for identifying patients with true OMD, or at risk of metastatic disease likely to be OM.
Alessandrino F, Taghipour M, Hassanzadeh E, Ziaei A, Vangel M, Fedorov A, Tempany CM, Fennessy FM. Predictive Role of PI-RADSv2 and ADC Parameters in Differentiating Gleason Pattern 3 + 4 and 4 + 3 Prostate Cancer. Abdom Radiol (NY). 2019;44 (1) :279-85.Abstract
PURPOSE: To compare the predictive roles of qualitative (PI-RADSv2) and quantitative assessment (ADC metrics), in differentiating Gleason pattern (GP) 3 + 4 from the more aggressive GP 4 + 3 prostate cancer (PCa) using radical prostatectomy (RP) specimen as the reference standard. METHODS: We retrospectively identified treatment-naïve peripheral (PZ) and transitional zone (TZ) Gleason Score 7 PCa patients who underwent multiparametric 3T prostate MRI (DWI with b value of 0,1400 and where unavailable, 0,500) and subsequent RP from 2011 to 2015. For each lesion identified on MRI, a PI-RADSv2 score was assigned by a radiologist blinded to pathology data. A PI-RADSv2 score ≤ 3 was defined as "low risk," a PI-RADSv2 score ≥ 4 as "high risk" for clinically significant PCa. Mean tumor ADC (ADC), ADC of adjacent normal tissue (ADC), and ADC (ADC/ADC) were calculated. Stepwise regression analysis using tumor location, ADC and ADC, b value, low vs. high PI-RADSv2 score was performed to differentiate GP 3 + 4 from 4 + 3. RESULTS: 119 out of 645 cases initially identified met eligibility requirements. 76 lesions were GP 3 + 4, 43 were 4 + 3. ADC was significantly different between the two GP groups (p = 0.001). PI-RADSv2 score ("low" vs. "high") was not significantly different between the two GP groups (p = 0.17). Regression analysis selected ADC (p = 0.03) and ADC (p = 0.0007) as best predictors to differentiate GP 4 + 3 from 3 + 4. Estimated sensitivity, specificity, and accuracy of the predictive model in differentiating GP 4 + 3 from 3 + 4 were 37, 82, and 66%, respectively. CONCLUSIONS: ADC metrics could differentiate GP 3 + 4 from 4 + 3 PCa with high specificity and moderate accuracy while PI-RADSv2, did not differentiate between these patterns.
2018
Kurreck A, Vandergrift LA, Fuss TL, Habbel P, Agar NYR, Cheng LL. Prostate Cancer Diagnosis and Characterization with Mass Spectrometry Imaging. Prostate Cancer Prostatic Dis. 2018;21 (3) :297-305.Abstract
BACKGROUND: Prostate cancer (PCa), the most common cancer and second leading cause of cancer death in American men, presents the clinical challenge of distinguishing between indolent and aggressive tumors for proper treatment. PCa presents significant alterations in metabolic pathways that can potentially be measured using techniques like mass spectrometry (MS) or MS imaging (MSI) and used to characterize PCa aggressiveness. MS quantifies metabolomic, proteomic, and lipidomic profiles of biological systems that can be further visualized for their spatial distributions through MSI. METHODS: PubMed was queried for all publications relating to MS and MSI in human PCa from April 2007 to April 2017. With the goal of reviewing the utility of MSI in diagnosis and prognostication of human PCa, MSI articles that reported investigations of PCa-specific metabolites or metabolites indicating PCa aggressiveness were selected for inclusion. Articles were included that covered MS and MSI principles, limitations, and applications in PCa. RESULTS: We identified nine key studies on MSI in intact human prostate tissue specimens that determined metabolites which could either differentiate between benign and malignant prostate tissue or indicate PCa aggressiveness. These MSI-detected biomarkers show promise in reliably identifying PCa and determining disease aggressiveness. CONCLUSIONS: MSI represents an innovative technique with the ability to interrogate cancer biomarkers in relation to tissue pathologies and investigate tumor aggressiveness. We propose MSI as a powerful adjuvant histopathology imaging tool for prostate tissue evaluations, where clinical translation of this ex vivo technique could make possible the use of MSI for personalized medicine in diagnosis and prognosis of PCa. Moreover, the knowledge provided from this technique can majorly contribute to the understanding of molecular pathogenesis of PCa and other malignant diseases.
Arai S, Jonas O, Whitman MA, Corey E, Balk SP, Chen S. Tyrosine Kinase Inhibitors Increase MCL1 Degradation and in Combination with BCLXL/BCL2 Inhibitors Drive Prostate Cancer Apoptosis. Clin Cancer Res. 2018;24 (21) :5458-5470.Abstract
Clinically available BH3 mimetic drugs targeting BCLXL and/or BCL2 (navitoclax and venetoclax, respectively) are effective in some hematologic malignancies, but have limited efficacy in solid tumors. This study aimed to identify combination therapies that exploit clinical BH3 mimetics for prostate cancer. Prostate cancer cells or xenografts were treated with BH3 mimetics as single agents or in combination with other agents, and effects on MCL1 and apoptosis were assessed. MCL1 was also targeted directly using RNAi, CRISPR, or an MCL1-specific BH3 mimetic, S63845. We initially found that MCL1 depletion or inhibition markedly sensitized prostate cancer cells to apoptosis mediated by navitoclax, but not venetoclax, and , indicating that they are primed to undergo apoptosis and protected by MCL1 and BCLXL. Small-molecule EGFR kinase inhibitors (erlotinib, lapatinib) also dramatically sensitized to navitoclax-mediated apoptosis, and this was associated with markedly increased proteasome-dependent degradation of MCL1. This increased MCL1 degradation appeared to be through a novel mechanism, as it was not dependent upon GSK3β-mediated phosphorylation and subsequent ubiquitylation by the ubiquitin ligases βTRCP and FBW7, or through other previously identified MCL1 ubiquitin ligases or deubiquitinases. Inhibitors targeting additional kinases (cabozantinib and sorafenib) similarly caused GSK3β-independent MCL1 degradation, and in combination with navitoclax drove apoptosis and These results show that prostate cancer cells are primed to undergo apoptosis and that cotargeting BCLXL and MCL1, directly or indirectly through agents that increase MCL1 degradation, can induce dramatic apoptotic responses. .
Herrmann MD, Clunie DA, Fedorov A, Doyle SW, Pieper S, Klepeis V, Le LP, Mutter GL, Milstone DS, Schultz TJ, et al. Implementing the DICOM Standard for Digital Pathology. J Pathol Inform. 2018;9 :37.Abstract
Background: Digital Imaging and Communications in Medicine (DICOM) is the standard for the representation, storage, and communication of medical images and related information. A DICOM file format and communication protocol for pathology have been defined; however, adoption by vendors and in the field is pending. Here, we implemented the essential aspects of the standard and assessed its capabilities and limitations in a multisite, multivendor healthcare network. Methods: We selected relevant DICOM attributes, developed a program that extracts pixel data and pixel-related metadata, integrated patient and specimen-related metadata, populated and encoded DICOM attributes, and stored DICOM files. We generated the files using image data from four vendor-specific image file formats and clinical metadata from two departments with different laboratory information systems. We validated the generated DICOM files using recognized DICOM validation tools and measured encoding, storage, and access efficiency for three image compression methods. Finally, we evaluated storing, querying, and retrieving data over the web using existing DICOM archive software. Results: Whole slide image data can be encoded together with relevant patient and specimen-related metadata as DICOM objects. These objects can be accessed efficiently from files or through RESTful web services using existing software implementations. Performance measurements show that the choice of image compression method has a major impact on data access efficiency. For lossy compression, JPEG achieves the fastest compression/decompression rates. For lossless compression, JPEG-LS significantly outperforms JPEG 2000 with respect to data encoding and decoding speed. Conclusion: Implementation of DICOM allows efficient access to image data as well as associated metadata. By leveraging a wealth of existing infrastructure solutions, the use of DICOM facilitates enterprise integration and data exchange for digital pathology.
Fedorov A, Schwier M, Clunie D, Herz C, Pieper S, Kikinis R, Tempany C, Fennessy F. An Annotated Test-retest Collection of Prostate Multiparametric MRI. Sci Data. 2018;5 :180281.Abstract
Multiparametric Magnetic Resonance Imaging (mpMRI) is widely used for characterizing prostate cancer. Standard of care use of mpMRI in clinic relies on visual interpretation of the images by an expert. mpMRI is also increasingly used as a quantitative imaging biomarker of the disease. Little is known about repeatability of such quantitative measurements, and no test-retest datasets have been available publicly to support investigation of the technical characteristics of the MRI-based quantification in the prostate. Here we present an mpMRI dataset consisting of baseline and repeat prostate MRI exams for 15 subjects, manually annotated to define regions corresponding to lesions and anatomical structures, and accompanied by region-based measurements. This dataset aims to support further investigation of the repeatability of mpMRI-derived quantitative prostate measurements, study of the robustness and reliability of the automated analysis approaches, and to support development and validation of new image analysis techniques. The manuscript can also serve as an example of the use of DICOM for standardized encoding of the image annotation and quantification results.
Moreira P, Patel N, Wartenberg M, Li G, Tuncali K, Heffter T, Burdette EC, Iordachita I, Fischer GS, Hata N, et al. Evaluation of Robot-assisted MRI-guided Prostate Biopsy: Needle Path Analysis during Clinical Trials. Phys Med Biol. 2018;63 (20) :20NT02.Abstract
PURPOSE: While the interaction between a needle and the surrounding tissue is known to cause a significant targeting error in prostate biopsy leading to false-negative results, few studies have demonstrated how it impacts in the actual procedure. We performed a pilot study on robot-assisted MRI-guided prostate biopsy with an emphasis on the in-depth analysis of the needle-tissue interaction in-vivo. Methods: The data were acquired during in-bore transperineal prostate biopsies in patients using a 4 degrees-of-freedom (DoF) MRI-compatible robot. The anatomical structures in the pelvic area and the needle path were reconstructed from MR images, and quantitatively analyzed. We analyzed each structure individually and also proposed a mathematical model to investigate the influence of those structures in the targeting error using the mixed-model regression. Results: The median targeting error in 188 insertions (27 patients) was 6.3mm. Both the individual anatomical structure analysis and the mixed-model analysis showed that the deviation resulted from the contact between the needle and the skin as the main source of error. On contrary, needle bending inside the tissue (expressed as needle curvature) did not vary among insertions with targeting errors above and below the average. The analysis indicated that insertions crossing the bulbospongiosus presented a targeting error lower than the average. The mixed-model analysis demonstrated that the distance between the needle guide and the patient skin, the deviation at the entry point, and the path length inside the pelvic diaphragm had a statistically significant contribution to the targeting error (p<0.05). Conclusions: Our results indicate that the errors associated with the elastic contact between the needle and the skin were more prominent than the needle bending along the insertion. Our findings will help to improve the preoperative planning of transperineal prostate biopsies.
van Beek EJR, Kuhl C, Anzai Y, Desmond P, Ehman RL, Gong Q, Gold G, Gulani V, Hall-Craggs M, Leiner T, et al. Value of MRI in Medicine: More Than Just Another Test?. J Magn Reson Imaging. 2018.Abstract
There is increasing scrutiny from healthcare organizations towards the utility and associated costs of imaging. MRI has traditionally been used as a high-end modality, and although shown extremely important for many types of clinical scenarios, it has been suggested as too expensive by some. This editorial will try and explain how value should be addressed and gives some insights and practical examples of how value of MRI can be increased. It requires a global effort to increase accessibility, value for money, and impact on patient management. We hope this editorial sheds some light and gives some indications of where the field may wish to address some of its research to proactively demonstrate the value of MRI. LEVEL OF EVIDENCE: 5 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2018.
Beek JMRI 2018
King MT, Nguyen PL, Boldbaatar N, Tempany CM, Cormack RA, Beard CJ, Hurwitz MD, Suh WW, D'Amico AV, Orio PF. Long-Term Outcomes of Partial Prostate Treatment with Magnetic Resonance Imaging-Guided Brachytherapy for Patients with Favorable-Risk Prostate Cancer. Cancer. 2018;124 (17) :3528-35.Abstract
BACKGROUND: Partial prostate treatment has emerged as a potential method for treating patients with favorable-risk prostate cancer while minimizing toxicity. The authors previously demonstrated poor rates of biochemical disease control for patients with National Comprehensive Cancer Network (NCCN) intermediate-risk disease using partial gland treatment with brachytherapy. The objective of the current study was to estimate the rates of distant metastasis and prostate cancer-specific mortality (PCSM) for this cohort. METHODS: Between 1997 and 2007, a total of 354 men with clinical T1c disease, a prostate-specific antigen (PSA) level < 15 ng/mL, and Gleason grade ≤3 + 4 prostate cancer underwent partial prostate treatment with brachytherapy to the peripheral zone under 0.5-Tesla magnetic resonance guidance. The cumulative incidences of metastasis and PCSM for the NCCN very low-risk, low-risk, and intermediate-risk groups were estimated. Fine and Gray competing risk regression was used to evaluate clinical factors associated with time to metastasis. RESULTS: A total of 22 patients developed metastases at a median of 11.0 years (interquartile range, 6.9-13.9 years). The 12-year metastasis rates for patients with very low-risk, low-risk, and intermediate-risk disease were 0.8% (95% confidence interval [95% CI], 0.1%-4.4%), 8.7% (95% CI, 3.4%-17.2%), and 15.7% (95% CI, 5.7%-30.2%), respectively, and the 12-year PCSM estimates were 1.6% (95% CI, 0.1%-7.6%), 1.4% (95% CI, 0.1%-6.8%), and 8.2% (95% CI, 1.9%-20.7%), respectively. On multivariate analysis, NCCN risk category (low risk: hazard ratio, 6.34 [95% CI, 1.18-34.06; P = .03] and intermediate risk: hazard ratio, 6.98 [95% CI, 1.23-39.73; P = .03]) was found to be significantly associated with the time to metastasis. CONCLUSIONS: Partial prostate treatment with brachytherapy may be associated with higher rates of distant metastasis and PCSM for patients with intermediate-risk disease after long-term follow-up. Treatment of less than the full gland may not be appropriate for this cohort. Cancer 2018. © 2018 American Cancer Society.
Langkilde F, Kobus T, Fedorov A, Dunne R, Tempany C, Mulkern RV, Maier SE. Evaluation of Fitting Models for Prostate Tissue Characterization using Extended-range b-factor Diffusion-weighted Imaging. Magn Reson Med. 2018;79 (4) :2346-58.Abstract
PURPOSE: To compare the fitting and tissue discrimination performance of biexponential, kurtosis, stretched exponential, and gamma distribution models for high b-factor diffusion-weighted images in prostate cancer. METHODS: Diffusion-weighted images with 15 b-factors ranging from b = 0 to 3500 s/mmwere obtained in 62 prostate cancer patients. Pixel-wise signal decay fits for each model were evaluated with the Akaike Information Criterion (AIC). Parameter values for each model were determined within normal prostate and the index lesion. Their potential to differentiate normal from cancerous tissue was investigated through receiver operating characteristic analysis and comparison with Gleason score. RESULTS: The biexponential slow diffusion fraction f, the apparent kurtosis diffusion coefficient ADC, and the excess kurtosis factor K differ significantly among normal peripheral zone (PZ), normal transition zone (TZ), tumor PZ, and tumor TZ. Biexponential and gamma distribution models result in the lowest AIC, indicating a superior fit. Maximum areas under the curve (AUCs) of all models ranged from 0.93 to 0.96 for the PZ and from 0.95 to 0.97 for the TZ. Similar AUCs also result from the apparent diffusion coefficient (ADC) of a monoexponential fit to a b-factor sub-range up to 1250 s/mm. For kurtosis and stretched exponential models, single parameters yield the highest AUCs, whereas for the biexponential and gamma distribution models, linear combinations of parameters produce the highest AUCs. Parameters with high AUC show a trend in differentiating low from high Gleason score, whereas parameters with low AUC show no such ability. CONCLUSION: All models, including a monoexponential fit to a lower-b sub-range, achieve similar AUCs for discrimination of normal and cancer tissue. The biexponential model, which is favored statistically, also appears to provide insight into disease-related microstructural changes. Magn Reson Med 79:2346-2358, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
Hassanzadeh E, Alessandrino F, Olubiyi OI, Glazer DI, Mulkern RV, Fedorov A, Tempany CM, Fennessy FM. Comparison of Quantitative Apparent Diffusion Coefficient Parameters with Prostate Imaging Reporting and Data System V2 Assessment for Detection of Clinically Significant Peripheral Zone Prostate Cancer. Abdom Radiol (NY). 2018;43 (5) :1237-44.Abstract
PURPOSE: To compare diagnostic performance of PI-RADSv2 with ADC parameters to identify clinically significant prostate cancer (csPC) and to determine the impact of csPC definitions on diagnostic performance of ADC and PI-RADSv2. METHODS: We retrospectively identified treatment-naïve pathology-proven peripheral zone PC patients who underwent 3T prostate MRI, using high b-value diffusion-weighted imaging from 2011 to 2015. Using 3D slicer, areas of suspected tumor (T) and normal tissue (N) on ADC (b = 0, 1400) were outlined volumetrically. Mean ADCT, mean ADCN, ADCratio (ADCT/ADCN) were calculated. PI-RADSv2 was assigned. Three csPC definitions were used: (A) Gleason score (GS) ≥ 4 + 3; (B) GS ≥ 3 + 4; (C) MRI-based tumor volume >0.5 cc. Performances of ADC parameters and PI-RADSv2 in identifying csPC were measured using nonparametric comparison of receiver operating characteristic curves using the area under the curve (AUC). RESULTS: Eighty five cases met eligibility requirements. Diagnostic performances (AUC) in identifying csPC using three definitions were: (A) ADCT (0.83) was higher than PI-RADSv2 (0.65, p = 0.006); (B) ADCT (0.86) was higher than ADCratio (0.68, p < 0.001), and PI-RADSv2 (0.70, p = 0.04); (C) PI-RADSv2 (0.73) performed better than ADCratio (0.56, p = 0.02). ADCT performance was higher when csPC was defined by A or B versus C (p = 0.038 and p = 0.01, respectively). ADCratio performed better when csPC was defined by A versus C (p = 0.01). PI-RADSv2 performance was not affected by csPC definition. CONCLUSIONS: When csPC was defined by GS, ADC parameters provided better csPC discrimination than PI-RADSv2, with ADCT providing best result. When csPC was defined by MRI-calculated volume, PI-RADSv2 provided better discrimination than ADCratio. csPC definition did not affect PI-RADSv2 diagnostic performance.
2017
Verma S, Choyke PL, Eberhardt SC, Oto A, Tempany CM, Turkbey B, Rosenkrantz AB. The Current State of MR Imaging-targeted Biopsy Techniques for Detection of Prostate Cancer. Radiology. 2017;285 (2) :343-56.Abstract
Systematic transrectal ultrasonography (US)-guided biopsy is the standard approach for histopathologic diagnosis of prostate cancer. However, this technique has multiple limitations because of its inability to accurately visualize and target prostate lesions. Multiparametric magnetic resonance (MR) imaging of the prostate is more reliably able to localize significant prostate cancer. Targeted prostate biopsy by using MR imaging may thus help to reduce false-negative results and improve risk assessment. Several commercial devices are now available for targeted prostate biopsy, including in-gantry MR imaging-targeted biopsy and real-time transrectal US-MR imaging fusion biopsy systems. This article reviews the current status of MR imaging-targeted biopsy platforms, including technical considerations, as well as advantages and challenges of each technique.
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;209 (3) :W145-51.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.

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