August 2022

Hosseiny M, Sung KH, Felker E, Suvannarerg V, Tubtawee T, Shafa A, Arora KR, Ching J, Gulati A, Azadikhah A, Zhong X, Sayre J, Lu D, Raman SS.

OBJECTIVE: We aimed to investigate if the use of read-out segmented echoplanar imaging with additional two-dimensional navigator correction (Readout Segmentation of Long Variable Echo, RESOLVE) for acquiring prostate diffusion-weighted imaging (DWI) improves image quality, compared to single-shot echoplanar imaging (ss-EPI). METHODS: This single-center prospective study cohort included 162 males with suspected prostate cancer, who underwent 3 Tesla multiparametric MRI (3T-mpMRI). Two abdominal radiologists, blinded to the clinical information, separately reviewed each 3T-mpMRI study to rank geometrical distortion, degree of rectal distention, lesion conspicuity, and anatomic details delineation first on ss-EPI-DWI and later on RESOLVE-DWI using 5-point scales (1 = excellent, 5 = poor). The average of the ranking scores given by two readers was generated and used as the final score.

July 2022

Patel PM, Osadchiy V, Quirk M, Dunn MD, Donin NM.

Prostatic artery embolization (PAE) is an effective treatment for men with lower urinary symptoms (LUTS) caused by prostate enlargement, with proven improvement in symptoms and quality of life. Recently, the efficacy of PAE has been successfully demonstrated in massively enlarged glands [1]. It seems, however, that larger glands can present a potential issue due to the presence of a large median lobe, which has been associated with urinary obstruction after PAE [2]. We present the case of an extremely large and adherent devitalized adenomatous mass producing a ball valve effect within the prostatic fossa and causing recurrent urinary retention after PAE.

July 2022

Ruchalski K, Kim HJ, Douek M, Raman S, Patel M, Sai V, Gutierrez A, Levine B, Fischer C, Allen-Auerbach M, Gupta P, Coy H, Villegas B, Brown M, Goldin J.

BACKGROUND: To evaluate the anatomic site(s) of initial disease progression in patients with castration resistant metastatic prostate cancer (mCRPC) in the presence or absence of pre-treatment visceral metastases while on systemic therapy. METHODS: This is a retrospective cohort study of mCRPC patients who have baseline and at least one follow up bone scan and CT chest, abdomen and pelvis (CAP). Disease progression was determined by RECIST and/or ≥ 30% increase in automated bone scan lesion area score. Kaplan-Meier plot was used to estimate the median progression free survival and log-rank tests were used to compare anatomic sites.

May 2022

Khoo A, Liu LY, Sadun TY, Salmasi A, Pooli A, Felker E, Houlahan KE, Ignatchenko V, Raman SS, Sisk AE Jr, Reiter RE, Boutros PC, Kislinger T.

Multiparametric magnetic resonance imaging (mpMRI) is an emerging standard for diagnosing and prognosing prostate cancer, but ~ 20% of clinically significant tumors are invisible to mpMRI, as defined by the Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) score of one or two. To understand the biological underpinnings of tumor visibility on mpMRI, we examined the proteomes of forty clinically significant tumors (i.e., International Society of Urological Pathology (ISUP) Grade Group 2)-twenty mpMRI-visible and twenty mpMRI-invisible, with matched histologically normal prostate. Normal prostate tissue was indistinguishable between patients with visible and invisible tumors, and invisible tumors closely resembled the normal prostate. These data indicate that mpMRI-visibility arises when tumor evolution leads to large-magnitude proteomic divergences from histologically normal prostate.

April 2022

Kinnaird A, Yerram NK, O'Connor L, Brisbane W, Sharma V, Chuang R, Jayadevan R, Ahdoot M, Daneshvar M, Priester A, Delfin M, Tran E, Barsa DE, Sisk A, Reiter RE, Felker E, Raman S, Kwan L, Choyke PL, Merino MJ, Wood BJ, Turkbey B, Pinto PA, Marks LS.

PURPOSE: The underlying premise of prostate cancer active surveillance (AS) is that cancers likely to metastasize will be recognized and eliminated before cancer-related disease can ensue. Our study was designed to determine the prostate cancer upgrading rate when biopsy guided by magnetic resonance imaging (MRGBx) is used before entry and during AS. MATERIALS AND METHODS: The cohort included 519 men with low- or intermediate-risk prostate cancer who enrolled in prospective studies (NCT00949819 and NCT00102544) between February 2008 and February 2020. Subjects were preliminarily diagnosed with Gleason Grade Group (GG) 1 cancer; AS began when subsequent MRGBx confirmed GG1 or GG2. Participants underwent confirmatory MRGBx (targeted and systematic) followed by surveillance MRGBx approximately every 12 to 24 months. The primary outcome was tumor upgrading to ≥GG3.

March 2022

Kinnaird A, Brisbane W, Kwan L, Priester A, Chuang R, Barsa DE, Delfin M, Sisk A, Margolis D, Felker E, Hu J, Marks LS.

INTRODUCTION: A functional tool to optimize patient selection for magnetic resonance imaging (MRI)-guided prostate biopsy (MRGB) is an unmet clinical need. We sought to develop a prostate cancer risk calculator (PCRC-MRI) that combines MRI and clinical characteristics to aid decision-making for MRGB in North American men. METHODS: Two prospective registries containing 2354 consecutive men undergoing MRGB (September 2009 to April 2019) were analyzed. Patients were randomized into five groups, with one group randomly assigned to be the validation cohort against the other four groups as the discovery cohort. The primary outcome was detection of clinically significant prostate cancer (csPCa) defined as Gleason grade group ≥2. Variables included age, ethnicity, digital rectal exam (DRE), prior biopsy, prostate-specific antigen (PSA), prostate volume, PSA density, and MRI score. Odds ratios (OR) were calculated from multivariate logistic regression comparing two models: one with clinical variables only (clinical) against a second combining clinical variables with MRI data (clinical+MRI).

August 2021

Cao R, Zhong X, Afshari S, Felker E, Suvannarerg V, Tubtawee T, Vangala S, Scalzo F, Raman S, Sung K.

BACKGROUND: Several deep learning-based techniques have been developed for prostate cancer (PCa) detection using multiparametric magnetic resonance imaging (mpMRI), but few of them have been rigorously evaluated relative to radiologists' performance or whole-mount histopathology (WMHP). PURPOSE: To compare the performance of a previously proposed deep learning algorithm, FocalNet, and expert radiologists in the detection of PCa on mpMRI with WMHP as the reference. STUDY TYPE: Retrospective, single-center study. SUBJECTS: A total of 553 patients (development cohort: 427 patients; evaluation cohort: 126 patients) who underwent 3-T mpMRI prior to radical prostatectomy from October 2010 to February 2018. FIELD STRENGTH/SEQUENCE: 3-T, T2-weighted imaging and diffusion-weighted imaging. ASSESSMENT: FocalNet was trained on the development cohort to predict PCa locations by detection points, with a confidence value for each point, on the evaluation cohort. Four fellowship-trained genitourinary (GU) radiologists independently evaluated the evaluation cohort to detect suspicious PCa foci, annotate detection point locations, and assign a five-point suspicion score (1: least suspicious, 5: most suspicious) for each annotated detection point. The PCa detection performance of FocalNet and radiologists were evaluated by the lesion detection sensitivity vs. the number of false-positive detections at different thresholds on suspicion scores. Clinically significant lesions: Gleason Group (GG) ≥ 2 or pathological size ≥ 10 mm. Index lesions: the highest GG and the largest pathological size (secondary). STATISTICAL TESTS: Bootstrap hypothesis test for the detection sensitivity between radiologists and FocalNet.

March 2021

Klotz L, Pavlovich CP, Chin J, Hatiboglu G, Koch M, Penson D, Raman S, Oto A, Fütterer J, Serrallach M, Relle J, Lotan Y, Heidenreich A, Bonekamp D, Haider M, Tirkes T, Arora S, Macura KJ, Costa DN, Persigehl T, Pantuck AJ, Bomers J, Burtnyk M, Staruch R, Eggener S.

PURPOSE: Magnetic resonance imaging-guided transurethral ultrasound ablation uses directional thermal ultrasound under magnetic resonance imaging thermometry feedback control for prostatic ablation. We report 12-month outcomes from a prospective multicenter trial (TACT). MATERIALS AND METHODS: A total of 115 men with favorable to intermediate risk prostate cancer across 13 centers were treated with whole gland ablation sparing the urethra and apical sphincter. The co-primary 12-month endpoints were safety and efficacy.

March 2021

Murthy V, Sonni I, Jariwala N, Juarez R, Reiter RE, Raman SS, Hope TA.

CONTEXT: Prostate cancer (PCa) is the most common solid organ malignancy in men and is the third leading cause of cancer death. Accurate methods for the detection and staging of PCa are necessary to determine the extent of disease and inform treatment options. OBJECTIVE: To review the performance and diagnostic accuracy of prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging in the initial staging of PCa and evaluate its impact on definitive therapy planning. EVIDENCE ACQUISITION: A comprehensive literature search was performed using PubMed. References from retrieved articles and recommendations from the authors were also included.

February 2021

Pooli A, Johnson DC, Shirk J, Markovic D, Sadun TY, Sisk AE Jr, Mohammadian Bajgiran A, Afshari Mirak S, Felker ER, Hughes AK, Raman SS, Reiter RE.

PURPOSE: Oncologic efficacy of focal therapies in prostate cancer depends heavily on accurate tumor size estimation. We aim to evaluate the agreement between radiologic tumor size and pathological tumor size, and identify predictors of pathological tumor size. MATERIALS AND METHODS: This single arm study cohort included all consecutive patients with biopsy proven prostate cancer and a corresponding PI-RADS®v2 3 or greater index tumor on multiparametric magnetic resonance imaging who subsequently underwent radical prostatectomy. Radiologic tumor size was defined as maximum tumor diameter on multiparametric magnetic resonance imaging and compared to whole mount histopathology tumor correlates. The difference between radiologic tumor size and pathological tumor size was assessed, and clinical, pathological and radiographic predictors of pathological tumor size were examined.

December 2020

Roberts DG, Callese TE, Okafor E, Naik P, Harrison B, Tse G, Plotnik AN, McWilliams JP.

Benign prostatic hyperplasia (BPH) and ejaculatory dysfunction (EjD) are often comorbid conditions. However, most interventions for BPH worsen rather than alleviate EjD. Retrograde ejaculation, for example, is a frequent complication of transurethral resection of the prostate, occurring in more than 50% of patients (1). Over the past decade, prostatic artery embolization (PAE) has proven to be a safe and effective treatment alternative for BPH with lower urinary tract symptoms (2); however, less is known about the effects of PAE on ejaculatory function. While a number of studies have shown PAE to preserve ejaculatory function (1), 1 study reported EjD in 56% of patients (3), and other studies have not collected or reported ejaculatory function at all. There is a lack of standardized reporting in the interventional radiology literature to compare EjD across studies. While early evidence suggests that embolization technique and embolic particle size may play a role in the development of EjD, this has yet to be validated (4). The aim of this article was to emphasize the importance of standardized reporting of EjD before and after PAE via an initial institutional experience implementing patient-reported ejaculatory function evaluations using the validated, 4-item Male Sexual Health Questionnaire for Ejaculatory Dysfunction Short Form (MSHQ-EjD-SF).

November 2020

Mathevosian S, Cusumano LR, Moradzadeh N, Ranade A, Plotnik AN, McWilliams JP.

Prostatic artery identification during catheter angiography is of primary importance during prostatic artery embolization (PAE). Identifying the prostatic arterial supply is critical to procedural success and patient safety, and rapid identification can reduce radiation dose and procedural times (1). The origins of the prostatic arteries are highly variable with the majority arising from the internal pudendal artery (31.1%-34.1%), superior vesical artery (20.1%-28.7%), gluteal-pudendal trunk (17.8%), obturator artery (12.6%-18.9%), or common trunk with the middle rectal artery (8.4%), as noted in 2 studies evaluating a total of 436 internal iliac angiograms during PAE (1, 2). Right and left prostatic artery origins also commonly differ in the same patient (1). Given the challenge of identifying the prostatic artery, multiple studies have examined imaging features to aid in identification, including preoperative pelvic computed tomography (CT) angiography and intraoperative cone-beam CT in conjunction with digital subtraction angiography (3, 4). This study examined a method identifying the prostatic artery on 45° ipsilateral oblique angiography of the internal iliac artery, herein labeled the Crossing Obturator Sign (CrOb sign).

October 2020

Hosseiny M, Felker ER, Azadikhah A, Suvannarerg V, Sayre J, Ponzini D, Ahuja P, Lu D, Raman SS.

PURPOSE: To evaluate the diagnostic yield of 3T in-Bore magnetic resonance-guided biopsy (3T IB-MRGB) for detection of clinically significant prostate cancer (csPCa), based on assessment using the Prostate Imaging Reporting and Data System version 2.1 (PIRADSv2.1). MATERIALS AND METHODS: This single-center study examined individuals who underwent 3T multiparametric prostate magnetic resonance (MR) imaging and subsequent 3T IB-MRGB. The final study cohort included 379 men (with 475 targets) divided into 3 subcohorts: biopsy-naïve men (n = 123), individuals with a history of negative trans-rectal-ultrasonography (TRUS) biopsy results (n = 106), and men with low-grade PCa under active surveillance (n = 150). csPCa was defined as having a Gleason score (GS) ≥3+4.

September 2020

Hosseiny M, Shakeri S, Felker ER, Lu D, Sayre J, Ahuja P, Raman SS.

OBJECTIVE. The purpose of this study was to evaluate the rate of detection of clinically significant prostate cancer (csPCa), as assessed on the basis of Prostate Imaging Reporting and Data System version 2.1 (PI-RADSv2.1) guidelines, using 3-T in-bore MR-guided biopsy (MRGB) for a cohort of patients suspected of having csPCa despite having a history of recent negative transrectal ultrasound-guided biopsy results. MATERIALS AND METHODS. The cohort in this retrospective, single-center study was derived from a database of 330 patients who underwent multiparametric MRI (mpMRI) followed by in-bore transrectal 3-T MRGB. Seventy-nine patients (mean [± SD] age, 64.1 ± 8.6 years) with prior negative transrectal ultrasound-guided biopsy results and positive pre-MRGB mpMRI results (PI-RADS score ≥ 3) composed the final cohort. The rate of detection of PCa and csPCa (the latter of which was defined by a Gleason score of 3 + 4 or higher) was stratified according to updated PI-RADSv2.1 assessment.

2020

Neeman E, Salamon N, Rettig M.

Leptomeningeal carcinomatosis is a rare complication of prostate cancer. It is likely underdiagnosed as suggested by autopsy studies and is expected to become more prevalent with increasing survival of prostate cancer patients. Prostate cancer leptomeningeal carcinomatosis is associated with rapid functional decline and a median survival of approximately 1 month. Diagnosis is challenging because the clinical manifestations are varied, and no gold-standard diagnostic approach exists. Treatment of prostate cancer leptomeningeal carcinomatosis is not standardized and multiple approaches have been reported, mostly as case studies. Herein we report a case of a 73-year-old patient with metastatic castration-resistant prostate cancer who presented to our clinic with subacute cognitive decline, ataxia, and urinary incontinence, and was found to have leptomeningeal carcinomatosis.

August 2020

Zhang Z, Wu HH, Priester A, Magyar C, Afshari Mirak S, Shakeri S, Mohammadian Bajgiran A, Hosseiny M, Azadikhah A, Sung K, Reiter RE, Sisk AE, Raman S, Enzmann DR.

BACKGROUND: Microstructural MRI has the potential to improve diagnosis and characterization of prostate cancer (PCa), but validation with histopathology is lacking. Purpose To validate ex vivo diffusion-relaxation correlation spectrum imaging (DR-CSI) in the characterization of microstructural tissue compartments in prostate specimens from men with PCa by using registered whole-mount digital histopathology (WMHP) as the reference standard. MATERIALS & METHODS: Men with PCa who underwent 3-T MRI and robotic-assisted radical prostatectomy between June 2018 and January 2019 were prospectively studied. After prostatectomy, the fresh whole prostate specimens were imaged in patient-specific three-dimensionally printed molds by using 3-T MRI with DR-CSI and were then sliced to create coregistered WMHP slides. The DR-CSI spectral signal component fractions (f_A, f_B, f_C) were compared with epithelial, stromal, and luminal area fractions (f_epithelium, f_stroma, f_lumen) quantified in PCa and benign tissue regions. A linear mixed-effects model assessed the correlations between (f_A, f_B, f_C) and (f_epithelium, f_stroma, f_lumen), and the strength of correlations was evaluated by using Spearman correlation coefficients. Differences between PCa and benign tissues in terms of DR-CSI signal components and microscopic tissue compartments were assessed using two-sided t tests.

July 2020

Afshari Mirak S, Mohammadian Bajgiran A, Sung K, Asvadi NH, Markovic D, Felker ER, Lu D, Sisk A, Reiter RE, Raman SS.

PURPOSE: To investigate the role of qualitative and quantitative DCE-MRI parameters in prostate cancer (PCa) stratified by whole-mount histopathology (WMHP) Gleason score (GS) and PI-RADSv2. METHODS: This retrospective study included 323 PCa tumors in 254 men, who underwent 3T MRI prior to prostatectomy, 7/2009-12/2016. Qualitative DCE curve types included type 1 (progressive), type 2 (plateau) and type 3 (washout). Quantitative DCE-MRI pharmacokinetic (PK) parameters included Ktrans (influx volume transfer coefficient), Kep (efflux reflux rate constant) and iAUC (initial area under the curve). DCE-MRI features of true positive lesions were evaluated for overall, index, transition zone (TZ) and peripheral zone (PZ), based on GS grade (low = 6, high > 6) and PI-RADSv2 score using SPSSv24.

May 2020

Wibulpolprasert P, Raman SS, Hsu W, Margolis DJA, Asvadi NH, Khoshnoodi P, Moshksar A, Tan N, Ahuja P, Maehara CK, Sisk A, Sayre J, Lu DSK, Reiter RE.

OBJECTIVE. The objective of our study was to determine the performance of 3-T multiparametric MRI (mpMRI) for prostate cancer (PCa) detection and localization, stratified by anatomic zone and level, using Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) and whole-mount histopathology (WMHP) as reference. MATERIALS AND METHODS. Multiparametric MRI examinations of 415 consecutive men were compared with thin-section WMHP results. A genitourinary radiologist and pathologist collectively determined concordance. Two radiologists assigned PI-RADSv2 scores and sector location to all detected foci by consensus. Tumor detection rates were calculated for clinical and pathologic (tumor location and zone) variables. Both rigid and adjusted sector-matching models were used to account for fixation-related issues.

May 2020

Zhang Z, Moulin K, Aliotta E, Shakeri S, Afshari Mirak S, Hosseiny M, Raman S, Ennis DB, Wu HH.

BACKGROUND: Prostate diffusion-weighted imaging (DWI) using monopolar encoding is sensitive to eddy-current-induced distortion artifacts. Twice-refocused bipolar encoding suppresses eddy current artifacts, but increases echo time (TE), leading to lower signal-to-noise ratio (SNR). Optimization of the diffusion encoding might improve prostate DWI. PURPOSE: To evaluate eddy current nulled convex optimized diffusion encoding (ENCODE) for prostate DWI with minimal TE. STUDY TYPE: Prospective cohort study. POPULATION: A diffusion phantom, an ex vivo prostate specimen, 10 healthy male subjects (27 ± 3 years old), and five prostate cancer patients (62 ± 7 years old). FIELD STRENGTH/SEQUENCE: 3T; single-shot spin-echo echoplanar DWI. ASSESSMENT: Eddy-current artifacts, TE, SNR, apparent diffusion coefficient (ADC), and image quality scores from three independent readers were compared between monopolar, bipolar, and ENCODE prostate DWI for standard-resolution (1.6 × 1.6 mm2 , partial Fourier factor [pF] = 6/8) and higher-resolution protocols (1.6 × 1.6 mm2 , pF = off; 1.0 × 1.0 mm2 , pF = 6/8). STATISTICAL TESTING: SNR and ADC differences between techniques were tested with Kruskal-Wallis and Wilcoxon signed-rank tests (P < 0.05 considered significant).

April 2020

Guorgui J, Kinnaird A, Jayadevan R, Priester AM, Arnold CW, Marks LS.

OBJECTIVE: To detail the development of an electronic report that graphically conveys all relevant information from targeted prostate biopsy. METHODS: The Urology Integrated Diagnostic Report (Uro-IDR) is based on a published framework (RadPath) which enables the compilation of diagnostic data from urology, radiology, and pathology. Each component of the Uro-IDR is generated by the contributing clinician, is assembled in one document, and provides correlation of the 3 inputs at a glance. Upon completion, the Uro-IDR is automatically linked to the electronic medical record as an interactive file and can also be downloaded for offline sharing as a PDF.

December 2019

Felker ER, Raman SS, Lu DSK, Tuttle M, Margolis DJ, ElKhoury FF, Sayre J, Marks LS.

OBJECTIVE. The purpose of this study was to compare in a multireader manner the diagnostic accuracies of 3-T multiparametric MRI interpretation and serial prostate-specific antigen (PSA) measurement in predicting the presence of residual clinically significant prostate cancer after focal laser ablation. MATERIALS AND METHODS. Eighteen men had undergone focal laser ablation for low- or intermediate-risk prostate cancer as part of two National Cancer Institute-funded phase 1 clinical trials. Multiparametric MRI was performed immediately after and 6 and 12 months after focal laser ablation. Serial PSA measurements after focal laser ablation were recorded, and MRI-ultrasound fusion biopsy was performed 6 and 12 months after ablation and served as the reference standard. Multiparametric MRI was performed at 3 T with pelvic phased-array coils. T2-weighted, DW, and dynamic contrast-enhanced MR images were retrospectively assessed by two blinded radiologists using a 3-point Likert scale (0-2). Inter-reader agreement was assessed with the Cohen kappa statistic. The diagnostic accuracies of multiparametric MRI and PSA measurement were compared.

November 2019

Mathevosian S, Plotnik AN, McWilliams JP.

Eight patients with giant prostatic enlargement > 200 mL and lower urinary tract symptoms who underwent bilateral prostatic artery embolization (PAE) were reviewed. Mean prostate volume decreased from 318.2 mL to 212.2 mL (P < .01). At 5-month mean follow-up, International Prostate Symptom Score decreased by 16.7 points (P < .05), and urinary quality of life improved by 3.0 points (P < .01). Three of 4 catheter-dependent patients no longer needed catheterization after the procedure. No major complications were encountered. Preliminary results suggest PAE is safe and effective in patients with giant prostatic enlargement > 200 mL.

October 2019

Sung K.

BACKGROUND: An estimation of an intravascular dispersion parameter was previously proposed to improve the overall accuracy and precision of the model parameters, but the high computation complexity can limit its practical usability in prostate dynamic contrast-enhanced MRI (DCE-MRI). PURPOSE: To compare and evaluate the model fitting uncertainty and error in the model parameter estimation using different DCE-MRI analysis models and to evaluate the ability of the intravascular dispersion parameter to delineate between noncancerous and cancerous prostate tissue in the transition and peripheral zones. STUDY TYPE: Retrospective. POPULATION: Fifty-three patients who underwent radical prostatectomy. FIELD STRENGTH/SEQUENCE: 3 T/3D RF-spoiled gradient echo sequence. ASSESSMENT: The coefficient of variation was used to assess the model fitting uncertainty by adding random noise to the time-concentration curves, and the Akaike information criterion was used to assess the model fitting error. The parametric maps derived from four DCE-MRI analysis models were evaluated by evaluating the delineation between noncancerous tissue and prostate cancer or clinically significant prostate cancer. STATISTICAL TESTS: The receiver operating curve analysis was performed to compare the ability to delineate between noncancerous and prostate cancer tissue in the transition and peripheral zones.

October 2019

van Luijtelaar A, Greenwood BM, Ahmed HU, Barqawi AB, Barret E, Bomers JGR, Brausi MA, Choyke PL, Cooperberg MR, Eggener S, Feller JF, Frauscher F, George AK, Hindley RG, Jenniskens SFM, Klotz L, Kovacs G, Lindner U, Loeb S, Margolis DJ, Marks LS, May S, Mcclure TD, Montironi R, Nour SG, Oto A, Polascik TJ, Rastinehad AR, De Reyke TM, Reijnen JS, de la Rosette JJMCH, Sedelaar JPM, Sperling DS, Walser EM, Ward JF, Villers A, Ghai S, Fütterer JJ.

PURPOSE: To define the role of focal laser ablation (FLA) as clinical treatment of prostate cancer (PCa) using the Delphi consensus method. METHODS: A panel of international experts in the field of focal therapy (FT) in PCa conducted a collaborative consensus project using the Delphi method. Experts were invited to online questionnaires focusing on patient selection and treatment of PCa with FLA during four subsequent rounds. After each round, outcomes were displayed, and questionnaires were modified based on the comments provided by panelists. Results were finalized and discussed during face-to-face meetings.

September 2019

Quirk M, Srinivasa RN, McWilliams JP, Plotnik AN.

OBJECTIVE. The purpose of this study is to evaluate the performance of the apparent diffusion coefficient ratio (ADCratio; the ADC of the suspected prostate cancer [PCa] focus on MRI divided by the ADC in a noncancerous reference area) with that of conventional ADC for detection of high-grade PCa (Gleason score [GS] ≥ 3 + 4) versus low-grade PCa (GS = 3 + 3) with whole-mount (WM) histopathologic analysis used as a reference. MATERIALS AND METHODS. The cohort of this retrospective study included 218 men with 240 unilateral PCa lesions assessed by both 3-T multiparametric MRI and whole-mount histopathologic analysis. ROIs were placed on individual lesions verified by WM histopathologic analysis, to calculate the mean ADC (ADC_{tumor_mean}) and lowest ADC within each lesion (ADC_{tumor_min}), and within non-tumor-containing regions of the same tumor zone but on the contralateral side (ADC_benign), to calculate the background ADC. The ADCratio_mean (the ADC_{tumor_mean} divided by the ADC_benign) was calculated. The performance of individual ADC_tumor and ADCratio_mean values in discriminating PCa with a GS of 3 + 3 from PCa with a GS of 3 + 4 or greater was assessed using the AUC value.

September 2019

Johnson DC, Yang JJ, Kwan L, Barsa DE, Mirak SA, Pooli A, Sadun T, Jayadevan R, Zhou S, Priester AM, Natarajan S, Bajgiran AM, Shakeri S, Sisk A, Felker ER, Raman SS, Marks LS, Reiter RE.

BACKGROUND: Hemiablation is a less morbid treatment alternative for appropriately selected patients with unilateral prostate cancer (PCa). However, to the authors' knowledge, traditional diagnostic techniques inadequately identify appropriate candidates. In the current study, the authors quantified the accuracy for identifying hemiablation candidates using contemporary diagnostic techniques, including multiparametric magnetic resonance imaging (mpMRI) and MRI-fusion with complete systematic template biopsy. METHODS: A retrospective analysis of patients undergoing MRI and MRI-fusion prostate biopsy, including full systematic template biopsy, prior to radical prostatectomy in a single tertiary academic institution between June 2010 and February 2018 was performed. Hemiablation candidates had unilateral intermediate-risk PCa (Gleason score [GS] of 3+4 or 4+3, clinical T classification ≤T2, and prostate-specific antigen level <20 ng/dL) on MRI-fusion biopsy and 2) no contralateral highly or very highly suspicious Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) MRI lesions. Hemiablation candidates were inappropriately selected if pathologists identified contralateral GS ≥3+4 or high-risk ipsilateral PCa on prostatectomy. The authors tested a range of hemiablation inclusion criteria and performed multivariable analysis of preoperative predictors of undetected contralateral disease.

Augest 2019

Felker ER, Raman SS, Shakeri S, Mirak SA, Bajgiran AM, Kwan L, Khoshnoodi P, ElKhoury FF, Margolis DJA, Karow D, Lu DSK, White N, Marks LS.

OBJECTIVE. The purpose of this article is to evaluate restriction spectrum imaging (RSI) in men undergoing MRI-ultrasound fusion biopsy for suspected prostate cancer (PCa) and to compare the performance of RSI with that of conventional DWI. MATERIALS AND METHODS. One hundred ninety-eight biopsy-naïve men enrolled in a concurrent prospective clinical trial evaluating MRI-targeted prostate biopsy underwent multiparametric MRI with RSI. Clinical and imaging features were compared between men with and without clinically significant (CS) PCa (MRI-ultrasound fusion biopsy Gleason score ≥ 3 + 4). RSI z score and apparent diffusion coefficient (ADC) were correlated, and their diagnostic performances were compared.

August 2019

Simopoulos DN, Sisk AE Jr, Priester A, Felker ER, Kwan L, Delfin MK, Reiter RE, Marks LS.

OBJECTIVE: To study the relationship of maximum cancer core length (MCCL), on targeted biopsy (TB) of magnetic resonance imaging (MRI)-visible index lesions, to volume of that tumour found at radical prostatectomy (RP). PATIENTS AND METHODS: In all, 205 men undergoing fusion biopsy and RP were divided into two groups: 136 in whom the MCCL came from an index MRI-visible lesion (TB) and 69 in whom MCCL came from a non-targeted lesion (non-targeted biopsy [NTB]). MRI was 3-T multi-parametric and biopsy was via MRI-ultrasonography fusion.

July 2019

Houlahan KE, Salmasi A, Sadun TY, Pooli A, Felker ER, Livingstone J, Huang V, Raman SS, Ahuja P, Sisk AE Jr, Boutros PC, Reiter RE.

Multiparametric magnetic resonance imaging (mpMRI) has transformed the management of localized prostate cancer by improving identification of clinically significant disease at diagnosis. Approximately 20% of primary prostate tumors are invisible to mpMRI, and we hypothesize that this invisibility reflects fundamental molecular properties of the tumor. We therefore profiled the genomes and transcriptomes of 40 International Society of Urological Pathology grade 2 tumors: 20 mpMRI-invisible (Prostate Imaging-Reporting and Data System [PI-RADS] v2 <3) and 20 mpMRI-visible (PI-RADS v2 5) tumors. mpMRI-visible tumors were enriched in hallmarks of nimbosus, an aggressive pathological, molecular, and microenvironmental phenomenon in prostate cancer. These hallmarks included genomes with increased mutation density, a higher prevalence of intraductal carcinoma/cribriform architecture pathology, and altered abundance of 102 transcripts, including overexpression of noncoding RNAs such as SCHLAP1. Multiple small nucleolar RNAs (snoRNAs) were identified, and a snoRNA signature synergized with nimbosus hallmarks to discriminate visible from invisible tumors. These data suggest a confluence of aggressive molecular and microenvironmental phenomena underlie mpMRI visibility of localized prostate cancer. PATIENT SUMMARY: We examined the correlation between tumor biology and magnetic resonance imaging (MRI) visibility in a group of patients with low- intermediate-risk prostate cancer. We observed that MRI findings are associated with biological features of aggressive prostate cancer.

July 2019

Pomykala KL, Farolfi A, Hadaschik B, Fendler WP, Herrmann K.

According to SEER Cancer Statistics Review there are around 165,000 new prostate cancer cases estimated in 2018 accounting for 9.5% of all newly diagnosed cancers. Accurate staging of primary prostate cancer is important for therapy selection (local vs systemic). Recent developments in molecular imaging may significantly impact staging procedures and management. Accordingly, this article addresses the current clinical standard, discusses the areas of unmet clinical need for imaging and then summarizes the most commonlyused molecular imaging probes. Finally, the authors dare an outlook to the short-term future role of molecular imaging in primary staging of prostate cancer.

June 2019

Zhong X, Cao R, Shakeri S, Scalzo F, Lee Y, Enzmann DR, Wu HH, Raman SS, Sung K.

PURPOSE: The purpose of the study was to propose a deep transfer learning (DTL)-based model to distinguish indolent from clinically significant prostate cancer (PCa) lesions and to compare the DTL-based model with a deep learning (DL) model without transfer learning and PIRADS v2 score on 3 Tesla multi-parametric MRI (3T mp-MRI) with whole-mount histopathology (WMHP) validation. METHODS: With IRB approval, 140 patients with 3T mp-MRI and WMHP comprised the study cohort. The DTL-based model was trained on 169 lesions in 110 arbitrarily selected patients and tested on the remaining 47 lesions in 30 patients. We compared the DTL-based model with the same DL model architecture trained from scratch and the classification based on PIRADS v2 score with a threshold of 4 using accuracy, sensitivity, specificity, and area under curve (AUC). Bootstrapping with 2000 resamples was performed to estimate the 95% confidence interval (CI) for AUC.

June 2019

Zhong X, Shakeri S, Liu D, Sayre J, Raman SS, Wu HH, Sung K.

BACKGROUND: Variable flip angle (VFA) imaging is widely used for the estimation of T1 relaxation in the prostate, but may have limited repeatability and reproducibility due to its sensitivity to B1 + inhomogeneity. PURPOSE: To assess the repeatability and reproducibility of prostate T1 estimation with and without compensating for B1 + variation. STUDY TYPE: Prospective. POPULATION: Twenty-one volunteers were prospectively recruited and scanned twice on two 3 T MRI scanners, resulting in 84 VFA T1 exams. FIELD STRENGTH/SEQUENCE: 3 T/2D saturated turbo fast low angle shot (FLASH) and 3D dual-echo FLASH. ASSESSMENT: Two B1 + mapping techniques, including reference region VFA (RR-VFA) and saturated turbo FLASH (satTFL), were used for B1 + correction, and T1 maps with and without B1 + correction were tested for intrascanner repeatability and interscanner reproducibility. Volumetric regions of interest (ROIs) were drawn on the transition zone, peripheral zone of the prostate, and the obturator internus left and right muscles in the corresponding slices. STATISTICAL TESTS: The average T1 within each ROI for each scan was compared for both intra- and interscanner variability using concordance correlation coefficient and a Bland-Altman plot.

May 2019

Johnson DC, Raman SS, Mirak SA, Kwan L, Bajgiran AM, Hsu W, Maehara CK, Ahuja P, Faiena I, Pooli A, Salmasi A, Sisk A, Felker ER, Lu DSK, Reiter RE.

BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) undoubtedly affects the diagnosis and treatment of localized prostate cancer (CaP). However, clinicians need a better understanding of its accuracy and limitations in detecting individual CaP foci to optimize management. OBJECTIVE: To determine the per-lesion detection rate for CaP foci by mpMRI and identify predictors of tumor detection. DESIGN, SETTING, AND PARTICIPANTS: We carried out a retrospective analysis of a prospectively managed database correlating lesion-specific results from mpMRI co-registered with whole-mount pathology (WMP) prostatectomy specimens from June 2010 to February 2018. Participants include 588 consecutive patients with biopsy-proven CaP undergoing 3-T mpMRI before radical prostatectomy at a single tertiary institution. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We measured mpMRI sensitivity in detecting individual CaP and clinically significant (any Gleason score ≥7) CaP foci and predictors of tumor detection using multivariate analysis.

May 2019

McWilliams JP, Bilhim TA, Carnevale FC, Bhatia S, Isaacson AJ, Bagla S, Sapoval MR, Golzarian J, Salem R, McClure TD, Kava BR, Spies JB, Sabharwal T, McCafferty I, Tam AL.

April 2019

Zhou SR, Simopoulos DN, Jayadevan R, Felker ER, Delfin MK, Barsa DE, Kwan L, Marks LS.

OBJECTIVE: To investigate safety, efficacy, and quality of life impact of hemi-gland cryotherapy for clinically-significant prostate cancer (CaP), when patient selection and follow-up includes MRI-guided biopsy. METHODS: Twenty-nine men with unilateral CaP (all clinically significant with prostate volume <60 cc) were enrolled in a prospective observational trial of hemi-gland cryotherapy. Mean patient age was 68.7 years. Median prostate-specific antigen (PSA) was 6.6 ng/mL. MRI-guided biopsy (3T-MRI, Artemis US fusion) was used for diagnosis and repeated at 6-month follow-up in all men. Treatment was under general anesthesia using the BTG/Galil system. Validated questionnaires were used to determine effects of treatment on urinary and sexual function and quality of life.

March 2019

Mirak SA, Shakeri S, Bajgiran AM, Felker ER, Sung KH, Asvadi NH, Khoshnoodi P, Markovic D, Ponzini D, Ahuja P, Sisk A, Reiter RE, Lu D, Raman SS.

PURPOSE: We investigated the performance of 3 Tesla multiparametric magnetic resonance imaging with and without an endorectal coil to detect prostate cancer with a whole mount histopathology reference. MATERIALS AND METHODS: This retrospective HIPAA (Health Insurance Portability and Accountability Act) compliant, institutional review board approved, case-control study included patients who underwent 3 Tesla multiparametric magnetic resonance imaging with and without an endorectal coil from July 2009 to December 2016 prior to prostatectomy. The tumor detection rate was calculated for total and index lesions. Lesion magnetic resonance imaging and histopathology features were compared between the 2 groups. Using SPSS®, version 24 p <0.05 was considered significant.

March 2019

Mohammadian Bajgiran A, Afshari Mirak S, Shakeri S, Felker ER, Ponzini D, Ahuja P, Sisk AE, Lu DS, Raman SS.

PURPOSE: To determine the characteristics of missed prostate cancer (PCa) lesions on 3T multiparametric-MRI (mpMRI) based on PI-RADSv2 with whole-mount histopathology (WMHP) correlation. MATERIALS AND METHODS: This IRB-approved, HIPAA-compliant study, included 614 consecutive men with 3T mpMRI prior to prostatectomy at a single tertiary center between 12/2009 and 4/2017. Clinical, mpMRI, and pathologic features were obtained. PI-RADSv2-based MRI detected lesions were matched with previously finalized WMHP by a genitourinary (GU) radiologist and a GU pathologist. Patients with no mpMRI detected PCa lesion, but with at least one lesion ≥ 1 cm on WMHP, were reviewed retrospectively and assigned a PI-RADSv2 score. Tumor characteristics were compared between missed and detected lesions.

February 2019

Plotnik AN, Roberts DG, Srinivasa RN, McWilliams JP.

Urinary obstruction secondary to benign prostatic hyperplasia is a late manifestation of the disease, and a poor prognostic sign for responding to conservative therapies. Prostatic artery embolization - when performed successfully - can be an effective treatment for reducing obstructive urinary symptoms. Outlined in this report is the successful recanalization of a prostatic artery chronic total occlusion prior to embolization in an 89-year-old man with benign prostatic hyperplasia, who initially presented with urinary obstruction. Prostatic artery recanalization was possible using a specialized crossing technique from peripheral arterial disease interventions, and allowed for more distal embolization of the prostate gland. This technique may be useful when advanced atherosclerotic disease limits the feasibility and clinical success of prostatic artery embolization.

January 2019

Wu HH, Priester A, Khoshnoodi P, Zhang Z, Shakeri S, Afshari Mirak S, Asvadi NH, Ahuja P, Sung K, Natarajan S, Sisk A, Reiter R, Raman S, Enzmann D.

BACKGROUND: Patient-specific 3D-printed molds and ex vivo MRI of the resected prostate have been two important strategies to align MRI with whole-mount histopathology (WMHP) for prostate cancer (PCa) research, but the combination of these two strategies has not been systematically evaluated. PURPOSE: To develop and evaluate a system that combines patient-specific 3D-printed molds with ex vivo MRI (ExV) to spatially align in vivo MRI (InV), ExV, and WMHP in PCa patients. STUDY TYPE: Prospective cohort study. POPULATION: Seventeen PCa patients who underwent 3T MRI and robotic-assisted laparoscopic radical prostatectomy (RALP). FIELD STRENGTH/SEQUENCES: T2 -weighted turbo spin-echo sequences at 3T. ASSESSMENT: Immediately after RALP, the fresh whole prostate specimens were imaged in patient-specific 3D-printed molds by 3T MRI and then sectioned to create WMHP slides. The time required for ExV was measured to assess impact on workflow. InV, ExV, and WMHP images were registered. Spatial alignment was evaluated using: slide offset (mm) between ExV slice locations and WMHP slides; overlap of the 3D prostate contour on InV versus ExV using Dice's coefficient (0 to 1); and 2D target registration error (TRE, mm) between corresponding landmarks on InV, ExV, and WMHP. Data are reported as mean ± standard deviation (SD). STATISTICAL TESTING: Differences in 2D TRE before versus after registration were compared using the Wilcoxon signed-rank test (P < 0.05 considered significant).

November 2018

Asvadi NH, Afshari Mirak S, Mohammadian Bajgiran A, Khoshnoodi P, Wibulpolprasert P, Margolis D, Sisk A, Reiter RE, Raman SS.

PURPOSE: To evaluate 3T mpMRI characteristics of transition zone and peripheral zone index prostate cancer lesions stratified by Gleason Score and PI-RADSv2 with whole mount histopathology correlation. METHODS: An institution review board-approved, HIPAA-compliant single-arm observational study of 425 consecutive men with 3T mpMRI prior to radical prostatectomy from December 2009 to October 2016 was performed. A genitourinary radiologist and a genitourinary pathologist matched all lesions detected on whole mount histopathology with lesions concordant for size and location on 3T mpMRI. Differences in clinical, MRI parameters, and histopathology between transition zone and peripheral zone were determined and analyzed with X² and Mann-Whitney U test. AUC was measured.

November 2018

Li J, Speier W, Ho KC, Sarma KV, Gertych A, Knudsen BS, Arnold CW.

Automated Gleason grading is an important preliminary step for quantitative histopathological feature extraction. Different from the traditional task of classifying small pre-selected homogeneous regions, semantic segmentation provides pixel-wise Gleason predictions across an entire slide. Deep learning-based segmentation models can automatically learn visual semantics from data, which alleviates the need for feature engineering. However, performance of deep learning models is limited by the scarcity of large-scale fully annotated datasets, which can be both expensive and time-consuming to create. One way to address this problem is to leverage external weakly labeled datasets to augment models trained on the limited data. In this paper, we developed an expectation maximization-based approach constrained by an approximated prior distribution in order to extract useful representations from a large number of weakly labeled images generated from low-magnification annotations. This method was utilized to improve the performance of a model trained on a limited fully annotated dataset. Our semi-supervised approach trained with 135 fully annotated and 1800 weakly annotated tiles achieved a mean Jaccard Index of 49.5% on an independent test set, which was 14% higher than the initial model trained only on the fully annotated dataset.

September 2018

Nagarajan MB, Raman SS, Lo P, Lin WC, Khoshnoodi P, Sayre JW, Ramakrishna B, Ahuja P, Huang J, Margolis DJA, Lu DSK, Reiter RE, Goldin JG, Brown MS, Enzmann DR.

PURPOSE: We present a method for generating a T2 MR-based probabilistic model of tumor occurrence in the prostate to guide the selection of anatomical sites for targeted biopsies and serve as a diagnostic tool to aid radiological evaluation of prostate cancer. MATERIALS AND METHODS: In our study, the prostate and any radiological findings within were segmented retrospectively on 3D T2-weighted MR images of 266 subjects who underwent radical prostatectomy. Subsequent histopathological analysis determined both the ground truth and the Gleason grade of the tumors. A randomly chosen subset of 19 subjects was used to generate a multi-subject-derived prostate template. Subsequently, a cascading registration algorithm involving both affine and non-rigid B-spline transforms was used to register the prostate of every subject to the template. Corresponding transformation of radiological findings yielded a population-based probabilistic model of tumor occurrence. The quality of our probabilistic model building approach was statistically evaluated by measuring the proportion of correct placements of tumors in the prostate template, i.e., the number of tumors that maintained their anatomical location within the prostate after their transformation into the prostate template space.

December 2017

Felker ER, Raman SS, Margolis DJ, Lu DSK, Shaheen N, Natarajan S, Sharma D, Huang J, Dorey F, Marks LS.

OBJECTIVE: The objective of our study was to determine the clinical and MRI characteristics of clinically significant prostate cancer (PCA) (Gleason score ≥ 3 + 4) in men with Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) category 3 transition zone (TZ) lesions. MATERIALS AND METHODS: From 2014 to 2016, 865 men underwent prostate MRI and MRI/ultrasound (US) fusion biopsy (FB). A subset of 90 FB-naïve men with 96 PI-RADSv2 category 3 TZ lesions was identified. Patients were imaged at 3 T using a body coil. Images were assigned a PI-RADSv2 category by an experienced radiologist. Using clinical data and imaging features, we performed univariate and multivariate analyses to identify predictors of clinically significant PCA.

October 2017

Natarajan S, Jones TA, Priester AM, Geoghegan R, Lieu P, Delfin M, Felker E, Margolis DJA, Sisk A, Pantuck A, Grundfest W, Marks LS.

PURPOSE: Focal laser ablation is a potential treatment in some men with prostate cancer. Currently focal laser ablation is performed by radiologists in a magnetic resonance imaging unit (in bore). We evaluated the safety and feasibility of performing focal laser ablation in a urology clinic (out of bore) using magnetic resonance imaging-ultrasound fusion for guidance. MATERIALS AND METHODS: A total of 11 men with intermediate risk prostate cancer were enrolled in this prospective, institutional review board approved pilot study. Magnetic resonance imaging-ultrasound fusion was used to guide laser fibers transrectally into regions of interest harboring intermediate risk prostate cancer. Thermal probes were inserted for real-time monitoring of intraprostatic temperatures during laser activation. Multiparametric magnetic resonance imaging (3 Tesla) was done immediately after treatment and at 6 months along with comprehensive fusion biopsy.

April 2017

Tan N, Lin WC, Khoshnoodi P, Asvadi NH, Yoshida J, Margolis DJ, Lu DS, Wu H, Sung KH, Lu DY, Huang J, Raman SS.

PURPOSE: To determine the diagnostic yield of in-bore 3-T magnetic resonance (MR) imaging-guided prostate biopsy and stratify performance according to Prostate Imaging Reporting and Data System (PI-RADS) versions 1 and 2. MATERIALS AND METHODS: This study was HIPAA compliant and institution review board approved. In-bore 3-T MR-guided prostate biopsy was performed in 134 targets in 106 men who (a) had not previously undergone prostate biopsy, (b) had prior negative biopsy findings with increased prostate-specific antigen (PSA) level, or (c) had a prior history of prostate cancer with increasing PSA level. Clinical, diagnostic 3-T MR imaging was performed with in-bore guided prostate biopsy, and pathology data were collected. The diagnostic yields of MR-guided biopsy per patient and target were analyzed, and differences between biopsy targets with negative and positive findings were determined. Results of logistic regression and areas under the curve were compared between PI-RADS versions 1 and 2.

March 2017

Nassiri N, Margolis DJ, Natarajan S, Sharma DS, Huang J, Dorey FJ, Marks LS.

PURPOSE: We sought to determine the rate of upgrading to Gleason score 4 + 3 or greater using targeted biopsy for diagnosis and monitoring in men undergoing active surveillance of prostate cancer. MATERIALS AND METHODS: Study subjects comprised all 259 men, including 196 with Gleason score 3 + 3 and 63 with Gleason score 3 + 4, who were diagnosed by magnetic resonance imaging/ultrasound fusion guided biopsy from 2009 to 2015 and underwent subsequent fusion biopsy for as long as 4 years of active surveillance. The primary end point was the discovery of Gleason score 4 + 3 or greater prostate cancer. Followup biopsies included targeting of positive sites, which were tracked in an Artemis™ device. Kaplan-Meier curves were generated to determine upgrading rates, stratified by initial Gleason score and prostate specific antigen density.

February 2017

Priester A, Natarajan S, Khoshnoodi P, Margolis DJ, Raman SS, Reiter RE, Huang J, Grundfest W, Marks LS.

PURPOSE: We evaluated the accuracy of magnetic resonance imaging in determining the size and shape of localized prostate cancer. MATERIALS AND METHODS: The subjects were 114 men who underwent multiparametric magnetic resonance imaging before radical prostatectomy with patient specific mold processing of the specimen from 2013 to 2015. T2-weighted images were used to contour the prostate capsule and cancer suspicious regions of interest. The contours were used to design and print 3-dimensional custom molds, which permitted alignment of excised prostates with magnetic resonance imaging scans. Tumors were reconstructed in 3 dimensions from digitized whole mount sections. Tumors were then matched with regions of interest and the relative geometries were compared.

September 2016

Rosenkrantz AB, Ginocchio LA, Cornfeld D, Froemming AT, Gupta RT, Turkbey B, Westphalen AC, Babb JS, Margolis DJ.

Purpose To determine the interobserver reproducibility of the Prostate Imaging Reporting and Data System (PI-RADS) version 2 lexicon. Materials and Methods This retrospective HIPAA-compliant study was institutional review board-approved. Six radiologists from six separate institutions, all experienced in prostate magnetic resonance (MR) imaging, assessed prostate MR imaging examinations performed at a single center by using the PI-RADS lexicon. Readers were provided screen captures that denoted the location of one specific lesion per case. Analysis entailed two sessions (40 and 80 examinations per session) and an intersession training period for individualized feedback and group discussion. Percent agreement (fraction of pairwise reader combinations with concordant readings) was compared between sessions. k coefficients were computed. Results No substantial difference in interobserver agreement was observed between sessions, and the sessions were subsequently pooled. Agreement for PI-RADS score of 4 or greater was 0.593 in peripheral zone (PZ) and 0.509 in transition zone (TZ). In PZ, reproducibility was moderate to substantial for features related to diffusion-weighted imaging (k = 0.535-0.619); fair to moderate for features related to dynamic contrast material-enhanced (DCE) imaging (k = 0.266-0.439); and fair for definite extraprostatic extension on T2-weighted images (k = 0.289). In TZ, reproducibility for features related to lesion texture and margins on T2-weighted images ranged from 0.136 (moderately hypointense) to 0.529 (encapsulation). Among 63 lesions that underwent targeted biopsy, classification as PI-RADS score of 4 or greater by a majority of readers yielded tumor with a Gleason score of 3+4 or greater in 45.9% (17 of 37), without missing any tumor with a Gleason score of 3+4 or greater. Conclusion Experienced radiologists achieved moderate reproducibility for PI-RADS version 2, and neither required nor benefitted from a training session. Agreement tended to be better in PZ than TZ, although was weak for DCE in PZ. The findings may help guide future PI-RADS lexicon updates.

July 2016

Felker ER, Margolis DJ, Nassiri N, Marks LS.

In recent years, multiparametric magnetic resonance imaging (mpMRI) has shown promise for prostate cancer (PCa) risk stratification. mpMRI, often followed by targeted biopsy, can be used to confirm low-grade disease before enrollment in active surveillance. In patients with intermediate or high-risk PCa, mpMRI can be used to inform surgical management. mpMRI has sensitivity of 44% to 87% for detection of clinically significant PCa and negative predictive value of 63% to 98% for exclusion of significant disease. In addition to tumor identification, mpMRI has also been shown to contribute significant incremental value to currently used clinical nomograms for predicting extraprostatic extension. In combination with conventional clinical criteria, accuracy of mpMRI for prediction of extraprostatic extension ranges from 92% to 94%, significantly higher than that achieved with clinical criteria alone. Supplemental sequences, such as diffusion-weighted imaging and dynamic contrast-enhanced imaging, allow quantitative evaluation of cancer-suspicious regions. Apparent diffusion coefficient appears to be an independent predictor of PCa aggressiveness. Addition of apparent diffusion coefficient to Epstein criteria may improve sensitivity for detection of significant PCa by as much as 16%. Limitations of mpMRI include variability in reporting, underestimation of PCa volume and failure to detect clinically significant disease in a small but significant number of cases.

July 2016

Natarajan S, Raman S, Priester AM, Garritano J, Margolis DJ, Lieu P, Macairan ML, Huang J, Grundfest W, Marks LS.

PURPOSE: Focal laser ablation is an investigational technique to treat prostate cancer in a region confined manner via coagulative necrosis. This phase I trial primarily examines the safety of transrectal magnetic resonance imaging guided (in-bore) focal laser ablation in men with intermediate risk prostate cancer. An exploratory end point is cancer control after 6 months. MATERIALS AND METHODS: In an institutional review board approved trial we studied focal laser ablation in 8 men with intermediate risk prostate cancer diagnosed using magnetic resonance-ultrasound fusion. Focal laser ablation was performed by inserting a cylindrically diffusing, water cooled laser fiber into magnetic resonance visible regions of interest, followed by interstitial heating at 10 to 15 W for up to 3 minutes. Secondary safety monitors (thermal probes) were inserted to assess the accuracy of magnetic resonance thermometry. Comprehensive magnetic resonance-ultrasound fusion biopsy was performed after 6 months. Adverse events and health related quality of life questionnaires were recorded.

June 2016

Margolis DJ.

The leading application of multiparametric magnetic resonance imaging (mpMRI) of the prostate is for lesion detection with the intention of tissue sampling (biopsy). Although direct in-bore magnetic resonance (MR)-guided biopsy allows for confirmation of the biopsy site, this can be expensive, time-consuming, and most importantly limited in availability. MR-transrectal ultrasound (MR-TRUS) image fusion targeted biopsy (TBx) allows for lesions identified on MRI to be targeted with the ease, efficiency, and availability of ultrasound.The learning objectives are optimized mpMRI protocol and reporting for image fusion targeted biopsy; methods of TRUS TBx; performance and limitations of MR-TRUS TBx; future improvements and applications.

May 2016

Felker ER, Lee-Felker SA, Feller J, Margolis DJ, Lu DS, Princenthal R, May S, Cohen M, Huang J, Yoshida J, Greenwood B, Kim HJ, Raman SS.

PURPOSE: To determine the safety and efficacy of in-bore magnetic resonance-guided prostate biopsy (MRGB) for detection of clinically significant disease (CSD) in untreated men with known or suspected prostate cancer (PCa). METHODS: 512 patients underwent multiparametric magnetic resonance imaging (Mp-MRI) followed by MRGB at one of three centers in this IRB-approved, HIPAA-compliant, retrospective study. Exclusion criteria were prior prostate cancer therapy and incomplete Mp-MRI (n = 51). Patients (n = 461) were analyzed in two subcohorts: no prior PCa (NP) (n = 381) and active surveillance (AS) (n = 80). Detection rates of PCa and CSD (Gleason Score ≥3 + 4) were calculated and compared among subcohorts and by Mp-MRI assessment grade. Logistic regression was performed to identify predictors for detection of PCa and CSD.

May 2016

Felker ER, Wu J, Natarajan S, Margolis DJ, Raman SS, Huang J, Dorey F, Marks LS.

PURPOSE: We assessed whether changes in serial multiparametric magnetic resonance imaging can help predict the pathological progression of prostate cancer in men on active surveillance. MATERIALS AND METHODS: A retrospective cohort study was conducted of 49 consecutive men with Gleason 6 prostate cancer who underwent multiparametric magnetic resonance imaging at baseline and again more than 6 months later, each followed by a targeted prostate biopsy, between January 2011 and May 2015. We evaluated whether progression on multiparametric magnetic resonance imaging (an increase in index lesion suspicion score, increase in index lesion volume or decrease in index lesion apparent diffusion coefficient) could predict pathological progression (Gleason 3 + 4 or greater on subsequent biopsy, in systematic or targeted cores). Diagnostic performance of multiparametric magnetic resonance imaging was determined with and without clinical data using a binary logistic regression model.

May 2016

Margolis DJ, Westphalen AC, Haider MA.

Despite being the most common non-cutaneous cancer and second leading cause of cancer death in American men, the United States Preventive Service Task Force recommends against screening for prostate cancer because of the resultant overtreatment of indolent disease [1]. With the demonstrated ability of multiparametric MRI (mpMRI) to identify cancer and the ability of mpMRI combined with transrectal ultrasound (TRUS) MRI fusion biopsy to increase the yield of significant cancer while decreasing the yield of insignificant cancer, there has been marked growth in volumes and indications for mpMRI of the prostate [2]. TRUS/MRI technology is growing in popularity and acceptance, and it will soon become the standard of care. The National Comprehensive Cancer Network, for example, is expected to suggest its appropriateness for initial biopsy and has recently advocated its use in active surveillance. Building on the demonstration of TRUS/MRI fusion at the National Institutes of Health, we now have nearly a dozen different systems for TRUS/MRI fusion biopsy [3]. This embarrassment of riches has come with an unexpected price—a similar number of commercial contour encoding systems and their associated workstations and image interpretation platforms have been developed for the segmentation of the prostate and suspicious regions within. Two immediate issues arise without vendor neutral specifications for handling contour metadata: the first is related to the problem of multiple referrers using multiple different TRUS/MRI fusion systems for targeted biopsy and its impact on workflow; the second related to archiving, retrieval, and transfer of patient data.

February 2016

Laviana AA, Ilg AM, Veruttipong D, Tan HJ, Burke MA, Niedzwiecki DR, Kupelian PA, King CR, Steinberg ML, Kundavaram CR, Kamrava M, Kaplan AL, Moriarity AK, Hsu W, Margolis DJ, Hu JC, Saigal CS.

BACKGROUND: Given the costs of delivering care for men with prostate cancer remain poorly described, this article reports the results of time-driven activity-based costing (TDABC) for competing treatments of low-risk prostate cancer. METHODS: Process maps were developed for each phase of care from the initial urologic visit through 12 years of follow-up for robotic-assisted laparoscopic prostatectomy (RALP), cryotherapy, high-dose rate (HDR) and low-dose rate (LDR) brachytherapy, intensity-modulated radiation therapy (IMRT), stereotactic body radiation therapy (SBRT), and active surveillance (AS). The last modality incorporated both traditional transrectal ultrasound (TRUS) biopsy and multiparametric-MRI/TRUS fusion biopsy. The costs of materials, equipment, personnel, and space were calculated per unit of time and based on the relative proportion of capacity used. TDABC for each treatment was defined as the sum of its resources.

January 2016

Barentsz JO, Weinreb JC, Verma S, Thoeny HC, Tempany CM, Shtern F, Padhani AR, Margolis D, Macura KJ, Haider MA, Cornud F, Choyke P.L

Rapid technical advances have enabled multiparametric magnetic resonance imaging (mpMRI) combined with magnetic resonance (MR)–targeted biopsy to become valuable tools for early detection of clinically significant prostate cancer (PCa) while reducing overdiagnosis of indolent PCa. There has been concern, however, that the widespread implementation and acceptance of mpMRI could be impaired by a lack of standardisation of image acquisition, interpretation and reporting guidance, and inter- and intraobserver variability that could result in poor clinical test performance in daily practise.

January 2016

Weinreb JC, Barentsz JO, Choyke PL, Cornud F, Haider MA, Macura KJ, Margolis D, Schnall MD, Shtern F, Tempany CM, Thoeny HC, Verma S.

The Prostate Imaging - Reporting and Data System Version 2 (PI-RADS^TM v2) is the product of an international collaboration of the American College of Radiology (ACR), European Society of Uroradiology (ESUR), and AdMetech Foundation. It is designed to promote global standardization and diminish variation in the acquisition, interpretation, and reporting of prostate multiparametric magnetic resonance imaging (mpMRI) examination, and it is based on the best available evidence and expert consensus opinion. It establishes minimum acceptable technical parameters for prostate mpMRI, simplifies and standardizes terminology and content of reports, and provides assessment categories that summarize levels of suspicion or risk of clinically significant prostate cancer that can be used to assist selection of patients for biopsies and management. It is intended to be used in routine clinical practice and also to facilitate data collection and outcome monitoring for research.

January 2016

Westphalen AC, Noworolski SM, Harisinghani M, Jhaveri KS, Raman SS, Rosenkrantz AB, Wang ZJ, Zagoria RJ, Kurhanewicz J.

OBJECTIVE: The goal of this study was to compare the perceived quality of 3-T axial T2-weighted high-resolution 2D and high-resolution 3D fast spin-echo (FSE) endorectal MR images of the prostate. MATERIALS AND METHODS: Six radiologists independently reviewed paired 3-T axial T2-weighted high-resolution 2D and 3D FSE endorectal MR images of the prostates of 85 men in two sessions. In the first session (n = 85), each reader selected his or her preferred images; in the second session (n = 28), they determined their confidence in tumor identification and compared the depiction of the prostatic anatomy, tumor conspicuity, and subjective intrinsic image quality of images. A meta-analysis using a random-effects model, logistic regression, and the paired Wilcoxon rank-sum test were used for statistical analyses.

November 2015

Kamrava M, Kishan AU, Margolis DJ, Huang J, Dorey F, Lieu P, Kupelian PA, Marks LS.

PURPOSE: Magnetic resonance imaging (MRI) guidance may improve the accuracy of Gleason score (GS) determination by directing the biopsy to regions of interest (ROI) that are likely to harbor high-grade prostate cancer (CaP). The aim of this study was to determine the frequency and predictors of GS upgrading when a subsequent MRI-guided biopsy is performed on patients with a diagnosis of GS 6 disease on the basis of conventional, transrectal ultrasound-guided biopsy. METHODS AND MATERIALS: A consecutive series of 245 men with a diagnosis of low-risk CaP (ie, cT1c, GS 6, prostate-specific antigen <10) based on transrectal ultrasound-guided biopsy was enrolled in an active surveillance protocol that used subsequent MRI-guided biopsy for confirmation of GS. ROIs were categorized on a scale of 1 to 5. The Artemis ultrasound-MRI fusion device was used to perform targeted biopsies of ROIs as well as systematic biopsies from a software-based 12-point map. Predictors of GS upgrading were analyzed using univariate and multivariate analyses.

November 2015

Nagarajan R, Iqbal Z, Burns B, Wilson NE, Sarma MK, Margolis DA, Reiter RE, Raman SS, Thomas MA.

The overlap of metabolites is a major limitation in one-dimensional (1D) spectral-based single-voxel MRS and multivoxel-based MRSI. By combining echo planar spectroscopic imaging (EPSI) with a two-dimensional (2D) J-resolved spectroscopic (JPRESS) sequence, 2D spectra can be recorded in multiple locations in a single slice of prostate using four-dimensional (4D) echo planar J-resolved spectroscopic imaging (EP-JRESI). The goal of the present work was to validate two different non-linear reconstruction methods independently using compressed sensing-based 4D EP-JRESI in prostate cancer (PCa): maximum entropy (MaxEnt) and total variation (TV). Twenty-two patients with PCa with a mean age of 63.8 years (range, 46-79 years) were investigated in this study. A 4D non-uniformly undersampled (NUS) EP-JRESI sequence was implemented on a Siemens 3-T MRI scanner. The NUS data were reconstructed using two non-linear reconstruction methods, namely MaxEnt and TV. Using both TV and MaxEnt reconstruction methods, the following observations were made in cancerous compared with non-cancerous locations: (i) higher mean (choline + creatine)/citrate metabolite ratios; (ii) increased levels of (choline + creatine)/spermine and (choline + creatine)/myo-inositol; and (iii) decreased levels of (choline + creatine)/(glutamine + glutamate). We have shown that it is possible to accelerate the 4D EP-JRESI sequence by four times and that the data can be reliably reconstructed using the TV and MaxEnt methods. The total acquisition duration was less than 13 min and we were able to detect and quantify several metabolites. Copyright © 2015 John Wiley & Sons, Ltd.

November 2015

Rakow-Penner RA, White NS, Margolis DJ, Parsons JK, Schenker-Ahmed N, Kuperman JM, Bartsch H, Choi HW, Bradley WG, Shabaik A, Huang J, Liss MA, Marks L, Kane CJ, Reiter RE, Raman SS, Karow DS, Dale AM.

PURPOSE: Diffusion imaging in the prostate is susceptible to distortion from B0 inhomogeneity. Distortion correction in prostate imaging is not routinely performed, resulting in diffusion images without accurate localization of tumors. We performed and evaluated distortion correction for diffusion imaging in the prostate. MATERIALS AND METHODS: 28 patients underwent pre-operative MRI (T2, Gadolinium perfusion, diffusion at b=800s/mm(2)). The restriction spectrum protocol parameters included b-values of 0, 800, 1500, and 4000s/mm(2) in 30 directions for each nonzero b-value. To correct for distortion, forward and reverse trajectories were collected at b=0s/mm(2). Distortion maps were generated to reflect the offset of the collected data versus the corrected data. Whole-mount histology was available for correlation.

September 2015

Nassiri N, Natarajan S, Margolis DJ, Marks LS.

Lessons learned during a 6-year experience with more than 1200 patients undergoing targeted prostate biopsy via MRI/ultrasound fusion are reported: (1) the procedure is safe and efficient, requiring some 15-20 minutes in an office setting; (2) MRI is best performed by a radiologist with specialized training, using a transabdominal multiparametric approach and preferably a 3T magnet; (3) grade of MRI suspicion is the most powerful predictor of biopsy results, eg, Grade 5 usually represents cancer; (4) some potentially important cancers (15%-30%) are MRI-invisible; (5) Targeted biopsies provide >80% concordance with whole-organ pathology. Early enthusiasm notwithstanding, cost-effectiveness is yet to be resolved, and the technologies remain in evolution.

August 2015

Brown AM, Elbuluk O, Mertan F, Sankineni S, Margolis DJ, Wood BJ, Pinto PA, Choyke PL, Turkbey B.

Prostate cancer is a common malignancy in the United States that results in over 30,000 deaths per year. The current state of prostate cancer diagnosis, based on PSA screening and sextant biopsy, has been criticized for both overdiagnosis of low-grade tumors and underdiagnosis of clinically significant prostate cancers (Gleason score ≥7). Recently, image guidance has been added to perform targeted biopsies of lesions detected on multi-parametric magnetic resonance imaging (mpMRI) scans. These methods have improved the ability to detect clinically significant cancer, while reducing the diagnosis of low-grade tumors. Several approaches have been explored to improve the accuracy of image-guided targeted prostate biopsy, including in-bore MRI-guided, cognitive fusion, and MRI/transrectal ultrasound fusion-guided biopsy. This review will examine recent advances in these image-guided targeted prostate biopsy techniques.

August 2015

Li L, Margolis DJ, Deng M, Cai J, Yuan L, Feng Z, Min X, Hu Z, Hu D, Liu J, Wang L.

BACKGROUND: To investigate tumor aggressiveness in peripheral zone prostate cancer (PCa) by correlating Gleason score (GS) with diffusion tensor imaging (DTI) from multiparametric magnetic resonance imaging (MRI) at 3.0 Tesla (T). METHODS: Eighty-three patients with pathological proven peripheral zone PCa whose GS in at least one core biopsy met the criteria(GS ≤ 3+3, GS 3+4, GS 4+3, or GS ≥ 4+4) were included in this study. DTI was performed using b values of 0 and 800 s/mm(2) with 32 directions in all patients on a 3.0T MRI scanner. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were calculated from the DTI data of patients with the previously mentioned four categories of Gleason scores. An association between DTI measurements(FA, ADC) and GS was tested using the Spearman rank correlation analysis.

July 2015

Billing A, Buchner A, Stief C, Roosen A.

PURPOSE: To evaluate the staging accuracy of preoperative multiparametric MRI (mp-MRI), its influence on the technique of radical retropubic prostatectomy (RRP), and its value for daily clinical practice. METHODS: A total of 106 patients underwent RRP (January 2011-June 2012) and had preoperative MRI staging data available for review. Staging results acquired by mp-MRI were correlated to both biopsy and histopathology results. Surgical reports were reviewed for intraoperative aspect of tumor extension, technique of RRP (nerve sparing or extended), and extent of lymphadenectomy.

July 2015

Tan N, Margolis DJ, Lu DY, King KG, Huang J, Reiter RE, Raman SS.

OBJECTIVE: The objective of this study was to determine the characteristics of prostate cancer foci missed on 3-T multiparametric MRI performed with an endorectal coil. MATERIALS AND METHODS: The MRI examinations of 122 patients who underwent 3-T multiparametric MRI of the prostate with an endorectal coil were compared with whole-mount histopathology obtained after radical prostatectomy. The mean age of the patients was 60.6 years (SD, 7.6 years), and the mean prostate-specific antigen value was 7.2 ng/mL (SD, 5.9 ng/mL). The clinical, multiparametric MRI (i.e., T2-weighted imaging, diffusion-weighted imaging, and dynamic contrast-enhanced imaging), and histopathologic features were obtained. After an independent review, two blinded genitourinary radiologists matched each case with a genitourinary pathologist. A structured reporting system was used to classify the multiparametric MRI features of each MRI-detected lesion. A chi-square analysis was performed for categoric variables, and the t test was performed for continuous variables.

March 2015

Le JD, Tan N, Shkolyar E, Lu DY, Kwan L, Marks LS, Huang J, Margolis DJ, Raman SS, Reiter RE.

BACKGROUND: Multiparametric magnetic resonance imaging (mp-MRI) is increasingly used in prostate cancer (CaP). Understanding the limitations of tumor detection, particularly in multifocal disease, is important in its clinical application. OBJECTIVE: To determine predictors of CaP detection by mp-MRI as confirmed by whole-mount histopathology. DESIGN, SETTING, AND PARTICIPANTS: A retrospective study was performed of 122 consecutive men who underwent mp-MRI before radical prostatectomy at a single referral academic center. A genitourinary radiologist and pathologist collectively determined concordance. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The odds of tumor detection were calculated for clinical, MRI, and histopathologic variables using a multivariate logistic regression model.

March 2015

Rakow-Penner RA, White NS, Parsons JK, Choi HW, Liss MA, Kuperman JM, Schenker-Ahmed N, Bartsch H, Mattrey RF, Bradley WG, Shabaik A, Huang J, Margolis DJ, Raman SS, Marks L, Kane CJ, Reiter RE, Karow DS, Dale AM.

Background:Standard magnetic resonance imaging (MRI) of the prostate lacks sensitivity in the diagnosis and staging of prostate cancer (PCa). To improve the operating characteristics of prostate MRI in the detection and characterization of PCa, we developed a novel, enhanced MRI diffusion technique using restriction spectrum imaging (RSI-MRI).Methods:We compared the efficacy of our novel RSI-MRI technique with standard MRI for detecting extraprostatic extension (EPE) among 28 PCa patients who underwent MRI and RSI-MRI prior to radical prostatectomy, 10 with histologically proven pT3 disease. RSI cellularity maps isolating the restricted isotropic water fraction were reconstructed based on all b-values and then standardized across the sample with z-score maps. Distortion correction of the RSI maps was performed using the alternating phase-encode technique.

November 2014

Le JD, Stephenson S, Brugger M, Lu DY, Lieu P, Sonn GA, Natarajan S, Dorey FJ, Huang J, Margolis DJ, Reiter RE, Marks LS.

PURPOSE: We explore the impact of magnetic resonance imaging-ultrasound fusion prostate biopsy on the prediction of final surgical pathology. MATERIALS AND METHODS: A total of 54 consecutive men undergoing radical prostatectomy at UCLA after fusion biopsy were included in this prospective, institutional review board approved pilot study. Using magnetic resonance imaging-ultrasound fusion, tissue was obtained from a 12-point systematic grid (mapping biopsy) and from regions of interest detected by multiparametric magnetic resonance imaging (targeted biopsy). A single radiologist read all magnetic resonance imaging, and a single pathologist independently rereviewed all biopsy and whole mount pathology, blinded to prior interpretation and matched specimen. Gleason score concordance between biopsy and prostatectomy was the primary end point.

October 2014

Chung MP, Margolis D, Mesko S, Wang J, Kupelian P, Kamrava M.

INTRODUCTION: The aim of this study was to determine if correlations exist between quantitative parameters from dynamic contrast-enhanced (DCE) and diffusion-weighted (DW) MRI with National Comprehensive Cancer Network (NCCN) risk group, Gleason score (GS), maximum tumour diameter (MTD), pre-treatment prostate-specific antigen (PSA), clinical T stage and MRI prostate volume in prostate cancer. METHOD: We retrospectively reviewed 3T multiparametric MRI reports on biopsy-proven prostate cancer patients performed during radiation treatment evaluation or an active surveillance protocol. DCE-MRI parameters included K(trans) (influx volume transfer coefficient), Kep (efflux reflux rate constant) and iAUC (initial area under the curve). Average DCE and apparent diffusion coefficient (ADC) values were recorded for regions of interest on DW-MRI. Relationships between MRI metrics and risk group, GS, MTD, PSA, clinical T stage and MRI prostate volume were examined using analysis of variance. Central and peripheral tumours were also analysed separately in a sub-analysis. Statistical significance was defined as P < 0.0125.

October 2014

Sonn GA, Filson CP, Chang E, Natarajan S, Margolis DJ, Macairan M, Lieu P, Huang J, Dorey FJ, Reiter RE, Marks LS.

OBJECTIVES: Targeted biopsy, using magnetic resonance (MR)-ultrasound (US) fusion, may allow tracking of specific cancer sites in the prostate. We aimed to evaluate the initial use of the technique to follow tumor sites in men on active surveillance of prostate cancer. METHODS AND MATERIALS: A total of 53 men with prostate cancer (all T1c category) underwent rebiopsy of 74 positive biopsy sites, which were tracked and targeted using the Artemis MR-US fusion device (Eigen, Grass Valley, CA) from March 2010 through January 2013. The initial biopsy included 12 cores from a standard template (mapped by software) and directed biopsies from regions of interest seen on MR imaging (MRI). In the repeat biopsy, samples were taken from sites containing cancer at the initial biopsy. Outcomes of interest at second MR-US biopsy included (a) presence of any cancer and (b) presence of clinically significant cancer.

August 2014

Hu JC, Chang E, Natarajan S, Margolis DJ, Macairan M, Lieu P, Huang J, Sonn G, Dorey FJ, Marks LS.

PURPOSE: Established in 1994, the Epstein histological criteria (Gleason score 6 or less, 2 or fewer cores positive and 50% or less of any core) have been widely used to select men for active surveillance. However, with the advent of targeted biopsy, which may be more accurate than conventional biopsy, we reevaluated the likelihood of reclassification upon confirmatory rebiopsy using multiparametric magnetic resonance imaging-ultrasound fusion. MATERIALS AND METHODS: We identified 113 men enrolled in active surveillance at our institution who met Epstein criteria and subsequently underwent confirmatory targeted biopsy via multiparametric magnetic resonance imaging-ultrasound fusion. Median patient age was 64 years, median prostate specific antigen was 4.2 ng/ml and median prostate volume was 46.8 cc. Targets or regions of interest on multiparametric magnetic resonance imaging-ultrasound fusion were graded by suspicion level and biopsied at 3 mm intervals along the longest axis (median 10.5 mm). Also, 12 systematic cores were obtained during confirmatory rebiopsy. Our reporting is consistent with START (Standards of Reporting for MRI-targeted Biopsy Studies) criteria.

August 2014

Sonn GA, Margolis DJ, Marks LS.

Recent advances in multiparametric magnetic resonance imaging (MRI) have enabled image-guided detection of prostate cancer. Fusion of MRI with real-time ultrasound (US) allows the information from MRI to be used to direct biopsy needles under US guidance in an office-based procedure. Fusion can be performed either cognitively or electronically, using a fusion device. Fusion devices allow superimposition (coregistration) of stored MRI images on real-time US images; areas of suspicion found on MRI can then serve as targets during US-guided biopsy. Currently available fusion devices use a variety of technologies to perform coregistration: robotic tracking via a mechanical arm with built-in encoders (Artemis/Eigen, BioJet/Geoscan); electromagnetic tracking (UroNav/Philips-Invivo, Hi-RVS/Hitachi); or tracking with a 3D US probe (Urostation/Koelis). Targeted fusion biopsy has been shown to identify more clinically significant cancers and fewer insignificant cancers than conventional biopsy. Fusion biopsy appears to be a major advancement over conventional biopsy because it allows (1) direct targeting of suspicious areas not seen on US and (2) follow-up biopsy of specific cancerous sites in men undergoing active surveillance.

May 2014

Anderson ES, Margolis DJ, Mesko S, Banerjee R, Wang PC, Demanes DJ, Kupelian P, Kamrava M.

PURPOSE: To assess the ability of multiparametric (mp) MRI (mp-MRI) to identify, stratify, and localize biopsy-proven prostate cancer lesions in a risk-stratified patient population. METHODS AND MATERIALS: We retrospectively analyzed 57 patients who had mp-MRI and core needle biopsy during diagnostic prostate cancer evaluation. The MRI sequences were scored for suspicion of cancer with a previously described system. Distributions of mp-MRI scores were compared across National Comprehensive Cancer Network prostate cancer risk groups. The mp-MRI-identified lesions were compared with the location of positive core needle biopsies to assess mp-MRI localization of true lesions.

April 2014

Sonn GA, Chang E, Natarajan S, Margolis DJ, Macairan M, Lieu P, Huang J, Dorey FJ, Reiter RE, Marks LS.

BACKGROUND: Conventional biopsy fails to detect the presence of some prostate cancers (PCas). Men with a prior negative biopsy but persistently elevated prostate-specific antigen (PSA) pose a diagnostic dilemma, as some harbor elusive cancer. OBJECTIVE: To determine whether use of magnetic resonance-ultrasound (MR-US) fusion biopsy results in improved detection of PCa compared to repeat conventional biopsy. DESIGN, SETTING, AND PARTICIPANTS: In a consecutive-case series, 105 subjects with prior negative biopsy and elevated PSA values underwent multiparametric magnetic resonance imaging (MRI) and fusion biopsy in an outpatient setting. INTERVENTION: Suspicious areas on multiparametric MRI were delineated and graded by a radiologist; MR-US fusion biopsy was performed by a urologist using the Artemis device; targeted and systematic biopsies were obtained regardless of MRI result. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Detection rates of all PCa and clinically significant PCa (Gleason ≥3+4 or Gleason 6 with maximal cancer core length ≥4 mm) were determined. The yield of targeted biopsy was compared to systematic biopsy. The ability of an MRI grading system to predict clinically significant cancer was investigated. Stepwise multivariate logistic regression analysis was performed to determine predictors of significant cancer on biopsy.

February 2014

Chamie K, Sonn GA, Finley DS, Tan N, Margolis DJ, Raman SS, Natarajan S, Huang J, Reiter RE.

OBJECTIVE: To determine whether multiparametric magnetic resonance imaging might improve the identification of patients with higher risk disease at diagnosis and thereby reduce the incidence of undergrading or understaging. METHODS: We retrospectively reviewed the clinical records of 115 patients who underwent multiparametric magnetic resonance imaging before radical prostatectomy. We used Epstein's criteria of insignificant disease with and without a magnetic resonance imaging (MRI) parameter (apparent diffusion coefficient) to calculate sensitivity, specificity, as well as negative and positive predictive values [NPV and PPV] across varying definitions of clinically significant cancer based on Gleason grade and tumor volume (0.2 mL, 0.5 mL, and 1.3 mL) on whole-mount prostate specimens. Logistic regression analysis was performed to determine the incremental benefit of MRI in delineating significant cancer.

January 2014

Thomas MA, Nagarajan R, Huda A, Margolis D, Sarma MK, Sheng K, Reiter RE, Raman SS.

Prostate cancer (PCa) is the second most common type of cancer among men in the United States. A major limitation in the management of PCa is an inability to distinguish, early on, cancers that will progress and become life threatening. One-dimensional (1D) proton ((1) H) MRS of the prostate provides metabolic information such as levels of choline (Ch), creatine (Cr), citrate (Cit), and spermine (Spm) that can be used to detect and diagnose PCa. Ex vivo high-resolution magic angle spinning (HR-MAS) of PCa specimens has revealed detection of more metabolites such as myo-inositol (mI), glutamate (Glu), and glutamine (Gln). Due to the J-modulation and signal overlap, it is difficult to quantitate Spm and other resonances in the prostate clearly by single- and multivoxel-based 1D MR spectroscopy. This limitation can be minimized by adding at least one more spectral dimension by which resonances can be spread apart, thereby increasing the spectral dispersion. However, recording of multivoxel-based two-dimensional (2D) MRS such as J-resolved spectroscopy (JPRESS) and correlated spectroscopy (L-COSY) combined with 2D or three-dimensional (3D) magnetic resonance spectroscopic imaging (MRSI) using conventional phase-encoding can be prohibitively long to be included in a clinical protocol. To reduce the long acquisition time required for spatial encoding, the echo-planar spectroscopic imaging (EPSI) technique has been combined with correlated spectroscopy to give four-dimensional (4D) echo-planar correlated spectroscopic imaging (EP-COSI) as well as J-resolved spectroscopic imaging (EP-JRESI) and the multi-echo (ME) variants. Further acceleration can be achieved using non-uniform undersampling (NUS) and reconstruction using compressed sensing (CS). Earlier versions of 2D MRS, theory of 2D MRS, spectral apodization filters, newer developments and the potential role of multidimensional MRS in PCa detection and management will be reviewed here.

October 2013

Moore CM, Kasivisvanathan V, Eggener S, Emberton M, Fütterer JJ, Gill IS, Grubb Iii RL, Hadaschik B, Klotz L, Margolis DJ, Marks LS, Melamed J, Oto A, Palmer SL, Pinto P, Puech P, Punwani S, Rosenkrantz AB, Schoots IG, Simon R, Taneja SS, Turkbey B, Ukimura O, van der Meulen J, Villers A, Watanabe Y; START Consortium.

BACKGROUND: A systematic literature review of magnetic resonance imaging (MRI)-targeted prostate biopsy demonstrates poor adherence to the Standards for the Reporting of Diagnostic Accuracy (STARD) recommendations for the full and transparent reporting of diagnostic studies. OBJECTIVE: To define and recommend Standards of Reporting for MRI-targeted Biopsy Studies (START). DESIGN, SETTING, AND PARTICIPANTS: Each member of a panel of 23 experts in urology, radiology, histopathology, and methodology used the RAND/UCLA appropriateness methodology to score a 258-statement premeeting questionnaire. The collated responses were presented at a face-to-face meeting, and each statement was rescored after group discussion. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Measures of agreement and consensus were calculated for each statement. The most important statements, based on group median score, the degree of group consensus, and the content of the group discussion, were used to create a checklist of reporting criteria (the START checklist).

August 2013

Finley DS, Margolis D, Raman SS, Ellingson BM, Natarajan S, Tan N, Huang J, Reiter RE.

OBJECTIVES: Robot-assisted radical prostatectomy (RARP) has now become the most common surgical treatment option for prostate cancer (CaP). Clinicopathologic data (i.e., biopsy, digital rectal exam, prostate specific antigen level) and patient-specific factors (e.g., age, erectile function, co-morbidities) are the primary sources of information that urologists use for counseling and treatment decision making. Magnetic resonance imaging (MRI) has evolved along a similar temporal arc to RARP, with increased utilization and precision over the past decade. MRI prior to RARP provides multifaceted adjunctive information, including enhancement of locoregional staging, delineation of spatial anatomic information, and identification of aberrant anatomy, all of which aid in patient treatment counseling and operative planning. This article is designed for urologic surgeons who perform RARP, with the aim of providing a review of prostate MRI imaging and highlighting findings which may specifically alter the operation.

April 2013

Kamrava M, Chung M, Mesko S, Wang J, Raman S, Margolis D, Marks L, Kupelian P.

To determine if there is a correlation between quantitative parameters from diffusion-weighted (DWI) and dynamic contrast-enhanced (DCE) MRI with NCCN risk group, Gleason score (GS), and maximum tumor diameter (MTD) in prostate cancer.

September 2012

Nagarajan R, Margolis D, Raman S, Sarma MK, Sheng K, King CR, Verma G, Sayre J, Reiter RE, Thomas MA.

PURPOSE: To investigate functional changes in prostate cancer patients with three pathologically proven different Gleason scores (GS) (3+3, 3+4, and 4+3) using magnetic resonance spectroscopic imaging (MRSI) and diffusion-weighted imaging (DWI). MATERIALS AND METHODS: In this study MRSI and DWI data were acquired in 41 prostate cancer patients using a 1.5T MRI scanner with a body matrix combined with an endorectal coil. The metabolite ratios of (Cho+Cr)/Cit were calculated from the peak integrals of total choline (Cho), creatine (Cr), and citrate (Cit) in MRSI. Apparent diffusion coefficient (ADC) values were derived from DWI for three groups of Gleason scores. The sensitivity and specificity of MRSI and DWI in patients were calculated using receiver operating characteristic curve (ROC) analysis.

August 2012

Tan N, Margolis DJ, McClure TD, Thomas A, Finley DS, Reiter RE, Huang J, Raman SS.

The introduction of serum prostate-specific antigen to the prostate cancer screening algorithm has led to an increase in prostate cancer diagnosis as well as a migration toward lower-stage cancer at the time of diagnosis. This stage migration has coincided with changes in treatment options; these include active surveillance, new therapies, and advances in surgical techniques. Use of robot-assisted radical prostatectomy (RARP) as a surgical technique has seen a significant increase over the past several years: the number of patients undergoing RARP has risen from 1% to 40% of all prostatectomies from 20012006 to as many as 80% in 2010. The robotic interface provides a 3D magnified view of the surgical field, intuitive instrument manipulation, motion scaling, tremor filtration, and excellent dexterity and range of motion. However, in some cases, the lack of tactile (haptic) feedback may limit the surgeon's decision making ability in assessing malignant involvement of the neurovascular bundles. Pre-operative planning relies on nomograms based on limited clinical and prostate biopsy information. The surgical decision to spare or resect the neurovascular bundles is based on clinical information which is not spatially or anatomically based. Advances in magnetic resonance imaging (MRI) may provide spatially localized information to fill this void and aid surgical planning, particularly for robotic surgeons. In this review, we discuss the potential role of pre-operative MRI in surgical planning for radical prostatectomy.

July 2012

Finley DS, Ellingson BM, Natarajan S, Zaw TM, Raman SS, Schulam P, Reiter RE, Margolis D.

OBJECTIVE: To evaluate the feasibility of diffusion tensor imaging (DTI) tractography of the prostate for mapping of periprostatic neurovascular anatomy. METHODS: Eight men with prostate cancer scheduled to undergo nerve-sparing robot-assisted radical prostatectomy (RARP) underwent endorectal multiparametric magnetic resonance imaging (MRI) of the prostate with DTI. Tract mapping was accomplished by positioning spherical regions of interest contiguously along the prostatic capsule at the prostatic apex, midgland, and base.

June 2012

Furuyama JK, Wilson NE, Burns BL, Nagarajan R, Margolis DJ, Thomas MA.

The application of compressed sensing is demonstrated in a recently implemented four-dimensional echo-planar based J-resolved spectroscopic imaging sequence combining two spatial and two spectral dimensions. The echo-planar readout simultaneously acquires one spectral and one spatial dimension. Therefore, the compressed sensing undersampling is performed along the indirectly acquired spatial and spectral dimensions, and the reconstruction is performed using the split Bregman algorithm, an efficient TV-minimization solver. The four-dimensional echo-planar-based J-resolved spectroscopic imaging data acquired in a prostate phantom containing metabolites at physiological concentrations are accurately reconstructed with as little as 20% of the original data. Experimental data acquired in six healthy prostates using the external body matrix "receive" coil on a 3T magnetic resonance imaging scanner are reconstructed with acquisitions using only 25% of the Nyquist-Shannon required amount of data, indicating the potential for a 4-fold acceleration factor in vivo, bringing the required scan time for multidimensional magnetic resonance spectroscopic imaging within clinical feasibility.

March 2012

McClure TD, Margolis DJ, Reiter RE, Sayre JW, Thomas MA, Nagarajan R, Gulati M, Raman SS.

PURPOSE: To determine whether findings at preoperative endorectal coil magnetic resonance (MR) imaging influence the decision to preserve neurovascular bundles and the extent of surgical margins in robotic-assisted laparoscopic prostatectomy (RALP). MATERIALS AND METHODS: This study was approved by the investigational review board and was compliant with the HIPAA; the requirement to obtain informed consent was waived. The authors prospectively evaluated 104 consecutive men with biopsy-proved prostate cancer who underwent preoperative endorectal coil MR imaging of the prostate and subsequent RALP. MR imaging was performed at 1.5 T between January 2004 and April 2008 and included T2-weighted imaging (n = 104), diffusion-weighted imaging (n = 88), dynamic contrast-enhanced imaging (n = 51), and MR spectroscopy (n = 91). One surgeon determined the planned preoperative extent of resection bilaterally on the basis of clinical information and then again after review of the final MR imaging report. The differences in the surgical plan before and after review of the MR imaging report were determined and compared with the actual surgical and pathologic results by using logistic regression analysis. Continuous and ranked variables underwent Pearson and Spearman analysis.

2012

Nagarajan R, Margolis D, Raman S, Sheng K, King C, Reiter R, Thomas MA.

The purpose of our study was to compare the apparent diffusion coefficient (ADC) derived from diffusion-weighted imaging (DWI) of prostate cancer (PCa) patients with three classes of pathological Gleason scores (GS). Patients whose GS met these criteria (GS 3 + 3, GS 3 + 4, and GS 4 + 3) were included in this study. The DWI was performed using b values of 0, 50, and 400s/mm(2) in 44 patients using an endorectal coil on a 1.5T MRI scanner. The apparent diffusion coefficient (ADC) values were calculated from the DWI data of patients with three different Gleason scores. In patients with a high-grade Gleason score (4 + 3), the ADC values were lower in the peripheral gland tissue, pathologically determined as tumor compared to low grade (3 + 3 and 3 + 4). The mean and standard deviation of the ADC values for patients with GS 3 + 3, GS 3 + 4, and GS 4 + 3 were 1.135 0.119, 0.976 0.103 and 0.831 0.087mm(2)/sec. The ADC values were statistically significant (P < 0.05) between the three different scores with a trend of decreasing ADC values with increasing Gleason scores by one-way ANOVA method. This study shows that the DWI-derived ADC values may help differentiate aggressive from low-grade PCa.

May-June 2011

Natarajan S, Marks LS, Margolis DJ, Huang J, Macairan ML, Lieu P, Fenster A.

OBJECTIVES: Prostate biopsy (Bx) has for 3 decades been performed in a systematic, but blind fashion using 2D ultrasound (US). Herein is described the initial clinical evaluation of a 3D Bx tracking and targeting device (Artemis; Eigen, Grass Valley, CA). Our main objective was to test accuracy of the new 3D method in men undergoing first and follow-up Bx to rule out prostate cancer (CaP). MATERIALS ANDd METHODS: Patients in the study were men ages 3587 years (66.1 9.9), scheduled for Bx to rule out CaP, who entered into an IRB-approved protocol. A total of 218 subjects underwent conventional trans-rectal US (TRUS); the tracking system was then attached to the US probe; the prostate was scanned and a 3D reconstruction was created. All Bx sites were visualized in 3D and tracked electronically. In 11 men, a pilot study was conducted to test ability of the device to return a Bx to an original site. In 47 men, multi-parametric 3 Tesla MRI, incorporating T2-weighted images, dynamic contrast enhancement, and diffusion-weighted imaging, was performed in advance of the TRUS, allowing the stored MRI images to be fused with real-time US during biopsy. Lesions on MRI were delineated by a radiologist, assigned a grade of CaP suspicion, and fused into TRUS for biopsy targeting.

April 2010

Nagarajan R, Gomez AM, Raman SS, Margolis DJ, McClure T, Thomas MA.

To determine the metabolite ratios of (Cho + Cr)/Cit and (Cho + Cr)/Spm in patients with two ranges of pathological Gleason scores, namely (3 + 4) and (4 + 3). By using the localized two-dimensional (2D) J-resolved spectroscopy (JPRESS) technique, the metabolites ratios can be calculated and correlated with prostate cancer aggressiveness. A total of 24 patients who underwent endorectal 2D JPRESS between April 2006 and July 2007 were included in this study. The 2D JPRESS voxel was localized predominantly in the peripheral zone suspected for malignancy based on pathology. Using the metabolites such as total choline (Cho), creatine (Cr), spermine (Spm) and citrate (Cit), the ratios (Cho + Cr)/Cit and (Cho + Cr)/Spm were calculated. In 14 prostate cancer patients who had a final pathologic Gleason scores of i) (3 + 4 = 7, n = 7) and ii) (4 + 3 = 7, n = 7), the metabolite ratios (mean +/- SD) of (Cho + Cr)/Cit and (Cho + Cr)/Spm were calculated using the 2D JPRESS spectra as follows: i) (1.48 +/- 0.83) and (1.59 +/- 0.73); ii) (2.90 +/- 0.94) and (2.71 +/- 1.47), respectively. Higher percentage of aggressive disease correlates with higher metabolites ratio. Our pilot study suggests that 2D JPRESS can be reliably evaluated in a clinical setting using an endorectal coil. In addition to the citrate ratio, the spermine ratio also correlates with pathology based Gleason score.

November 2008

Thomas MA, Lange T, Velan SS, Nagarajan R, Raman S, Gomez A, Margolis D, Swart S, Raylman RR, Schulte RF, Boesiger P.

OBJECTIVES: A major goal of this article is to summarize the current status of evaluating prostate metabolites non-invasively using spatially resolved two-dimensional (2D) MR Spectroscopy (MRS). MATERIALS AND METHODS: Due to various technical challenges, the spatially resolved versions of 2D MRS techniques are currently going through the developmental stage. During the last decade, four different versions of 2D MRS sequences have been successfully implemented on 3T and 1.5T MRI scanners manufactured by three different vendors. These sequences include half and maximum echo sampled J-resolved spectroscopy (JPRESS), S-PRESS and L-COSY, which are single volume localizing sequences, and the multi-voxel based JPRESS sequence.

November 2007

Margolis DJ, Hoffman JM, Herfkens RJ, Jeffrey RB, Quon A, Gambhir SS.

Molecular imaging of the body involves new techniques to image cellular biochemical processes, which results in studies with high sensitivity, specificity, and signal-to-background. The most prevalently used molecular imaging technique in body imaging is currently fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET). FDG PET has become the method of choice for the staging and restaging of many of the most common cancers, including lymphoma, lung cancer, breast cancer, and colorectal cancer. FDG PET has also become extremely valuable in monitoring the response to therapeutic drugs in many cancers. New PET agents, such as fluorothymidine and acetate, have also shown promise in the evaluation of response to therapy and in the staging of prostate cancer. Magnetic resonance (MR) spectroscopy has shown promise in the evaluation of prostate cancer. Breast cancer evaluation benefits from advances in spectroscopic imaging and contrast-enhanced kinetic evaluation of vascular permeability, which is altered in neoplastic processes because of release of angiogenic factors. Superparamagnetic iron oxide (SPIO) particles represent the first of an expanding line of MR contrast agents that target specific cellular processes. SPIO particles have also been used in the evaluation of the cirrhotic liver and at MR lymphangiography.

May 2005

Kim DH, Margolis D, Xing L, Daniel B, Spielman D.

In vivo magnetic resonance spectroscopic imaging of the prostate using single-voxel and multivoxel two-dimensional (2D) J-resolved sequences is investigated at a main magnetic field strength of 3 T. Citrate, an important metabolite often used to aid the detection of prostate cancer in magnetic resonance spectroscopic exams, can be reliably detected along with the other metabolites using this method. We show simulations and measurements of the citrate metabolite using 2D J-resolved spectroscopy to characterize the spectral pattern. Furthermore, using spiral readout gradients, the single-voxel 2D J-resolved method is extended to provide the spatial distribution information as well all within a reasonable scan time (17 min). Phantom and in vivo data are presented to illustrate the multivoxel 2D J-resolved spiral chemical shift imaging sequence.

September 2004

Sinha S, Sinha U.

This study demonstrates the feasibility of in vivo prostate diffusion tensor imaging (DTI) in human subjects. We implemented an EPI-based diffusion-weighted (DW) sequence with seven-direction diffusion gradient sensitization, and acquired DT images from six subjects using cardiac gating with a phased-array prostate surface coil operating in a linear mode. We calculated two indices to quantify diffusion anisotropy. The direction of the eigenvector corresponding to the leading eigenvalue was displayed by means of a color-coding scheme. The average diffusion values of the prostate peripheral zone (PZ) and central gland (CG) were 1.95 +/- 0.08 x 10(-3) mm2 s and 1.53 +/- 0.34 x 10(-3) mm2 s, respectively. The average fractional anisotropy (FA) values for the PZ and CG were 0.46 +/- 0.04 and 0.40 +/- 0.08, respectively. The diffusion ellipsoid in prostate tissue was anisotropic and approximated a prolate model, as shown in the color maps of the anisotropy. Consistent with the tissue architecture, the prostate fiber orientations were predominantly in the superior-inferior (SI) direction for both the PZ and CG. This study shows the feasibility of in vivo DTI and establishes normative DT values for six subjects.

Hricak H, Wang L, Wei DC, Coakley FV, Akin O, Reuter VE, Gonen M, Kattan MW, Onyebuchi CN, Scardino PT.

Ahmed HU, Kirkham A, Arya M, Illing R, Freeman A, Allen C, Emberton M.

Park BK, Lee HM, Kim CK, Choi HY, Park JW.

Singh AK, Kruecker J, Xu S, Glossop N, Guion P, Ullman K, Choyke PL, Wood BJ.