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Objective: The aim of this study was to determine and validate the optimal combination of parameters derived from 3-T diffusion-weighted imaging, dynamic contrast-enhanced imaging, and magnetic resonance (MR) spectroscopic imaging for discriminating low-grade from high-grade prostate cancer (PCa)., Materials and Methods: The study was approved by the institutional review board, and the need for informed consent was waived. Ninety-four patients with PCa who had undergone multiparametric MR imaging (MRI) before prostatectomy were included. Cancer was indicated on T2-weighted images, blinded to any functional data, with prostatectomy specimens as the reference standard. Tumors were classified as low grade or high grade based on Gleason score; peripheral zone (PZ) and transition zone (TZ) tumors were analyzed separately. In a development set (43 patients), the optimal combination of multiparametric MRI parameters was determined using logistic regression modeling. Subsequently, this combination was evaluated in a separate validation set (51 patients)., Results: In the PZ, the 25th percentile of apparent diffusion coefficient (ADC) derived from diffusion-weighted imaging and washout (WO25) derived from dynamic contrast-enhanced MRI offered the optimal combination of parameters. In the TZ, WO25 and the choline over spermine + creatine ratio (C/SC) derived from MR spectroscopic imaging showed the highest discriminating performance. Using the models built with the development set, 48 (74%) of 65 cancer lesions were classified correctly in the validation set., Conclusions: Multiparametric MRI is a useful tool for the discrimination between low-grade and high-grade PCa and performs better than any individual functional parameter in both the PZ and TZ. The 25th percentile of ADC + WO25 offered the optimal combination in the PZ, and the choline over spermine + creatine ratio + WO25 offered the optimal combination in the TZ. The ADC parameter has no additional value for the assessment of PCa aggressiveness in the TZ.

Objectives: The objective of this study was to evaluate the role of 3-T multiparametric magnetic resonance imaging (MP-MRI) and magnetic resonance-guided biopsy (MRGB) in early risk restratification of patients on active surveillance at 3 and 12 months of follow-up., Materials and Methods: Within 4 hospitals participating in a large active surveillance trial, a side study was initiated. Pelvic magnetic resonance imaging, prostate MP-MRI, and MRGB were performed at 3 and 12 months (latter prostate MP-MRI and MRGB only) after prostate cancer diagnosis in 1 of the 4 participating hospitals. Cancer-suspicious regions (CSRs) were defined on prostate MP-MRI using Prostate Imaging Reporting And Data System (PI-RADS) scores.Risk restratification criteria for active surveillance discontinuance were (1) histopathologically proven magnetic resonance imaging suspicion of node/bone metastases and/or (2) a Gleason growth pattern (GGP) 4 and/or 5 and/or cancer multifocality (≥3 foci) in MRGB specimens of a CSR on MP-MRI., Results: From 2009 to 2012, a total of 64 of 82 patients were consecutively and prospectively included and underwent MP-MRI and a subsequent MRGB. At 3 and 12 months of follow-up, 14% (9/64) and 10% (3/30) of the patients were risk-restratified on the basis of MP-MRI and MRGB. An overall CSR PI-RADS score of 1 or 2 had a negative predictive value of 84% (38/45) for detection of any prostate cancer and 100% (45/45) for detection of a GGP 4 or 5 containing cancer upon MRGB, respectively. A CSR PI-RADS score of 4 or higher had a sensitivity of 92% (11/12) for detection of a GGP 4 or 5 containing cancer upon MRGB., Conclusions: Application of MP-MRI and MRGB in active surveillance may contribute in early identification of patients with GGP 4 or 5 containing cancers at 3 months of follow-up. If, during further follow-up, a PI-RADS score of 1 or 2 continues to have a negative predictive value for GGP 4 or 5 containing cancers, a PI-RADS standardized reported MP-MRI may be a promising tool for the selection of prostate cancer patients suitable for active surveillance.

Objectives: The objective of this study was to evaluate the apparent diffusion coefficient (ADC) of diffusion-weighted magnetic resonance (MR) imaging for the differentiation of transition zone cancer from non-cancerous transition zone with and without prostatitis and for the differentiation of transition zone cancer Gleason grade (GG) using MR-guided biopsy specimens as a reference standard., Materials and Methods: From consecutive MR-guided prostate biopsies (2008-2012) in our referral center, we retrospectively included patients from whom diffusion-weighted MR imaging ADC values were acquired during MR-guided biopsy and whose biopsy cores had a (cancer) core length 10 mm or greater and originated from the transition zone. Two radiologists, who were blinded to the ADC data, annotated regions of interest on biopsy sampling locations of MR-guided biopsy confirmation scans in consensus. Median ADC (mADC) of the regions of interest was related to histopathology outcome in MR-guided biopsy core specimens. Mixed model analysis was used to evaluate mADC differences between 7 histopathology categories predefined as MR-guided biopsy core specimens with primary and secondary GG 4-5 (I), primary GG 4-5 secondary GG 2-3 (II), primary GG 2-3 secondary GG 4-5 (III) and primary and secondary GG 2-3 cancer (IV), and noncancerous tissue without (V) or with degree 1 (VI) or degree 2 prostatitis (VII). Diagnostic accuracy was evaluated using areas under the receiver operating characteristic (AUC) curve., Results: Fifty-two patients with 87 cancer-containing biopsy cores and 53 patients with 101 non-cancerous biopsy cores were included. Significant mean mADC differences were present between cancers (mean mADC, 0.77-0.86 × 10 mm/s) and noncancerous transition zone without (1.12 × 10 mm/s) and with degree 1 to 2 prostatitis (1.05-1.12 × 10 mm/s; P < 0.0001-0.05). Exceptions were mixed primary and secondary GG cancers versus a degree 2 of prostatitis (P = 0.06-0.09). No significant differences were found between subcategories of primary and secondary GG cancers (P = 0.17-0.91) and between a degree 1 and 2 prostatitis and non-cancerous transition zone without prostatitis (P = 0.48-0.94).The mADC had an AUC of 0.84 to differentiate cancer versus non-cancerous transition zone. AUCs of 0.84 and 0.56 were found for mADC to differentiate prostatitis from cancer and from non-cancerous transition zone. The mADC had an AUC of 0.62 to differentiate a primary GG 4 versus GG 3 cancer., Conclusions: The mADC values can differentiate transition zone cancer from non-cancerous transition zone and from a degree 1, and from most cases of a degree 2 prostatitis. However, because of substantial overlap, mADC has a moderate accuracy to differentiate between different primary and secondary GG subcategories and cannot be used to differentiate non-cancerous transition zone from degrees 1 to 2 of prostatitis. Diffusion-weighted imaging ADC may therefore contribute in the detection of transition zone cancers; however, as a single functional MR imaging technique, diffusion-weighted imaging has a moderate diagnostic accuracy in separating higher from lower GG transition zone cancers and in differentiating prostatitis from non-cancerous transition zone.

Purpose: We aimed to determine whether diffusion-weighted magnetic resonance imaging, by means of the apparent diffusion coefficient (ADC), is able to guide magnetic resonance-guided biopsy in patients fit for active surveillance (AS) and identify patients harboring high-grade Gleason components not suitable for AS., Materials and Methods: Our study was approved by the institutional review board of all participating hospitals, and all patients signed informed consent at inclusion. Fifty-four consecutive patients with low-risk prostate cancer (PCa) underwent multiparametric magnetic resonance imaging (MP-MRI) at inclusion for AS. Cancer-suspicious regions (CSRs) upon 3-T MP-MRI were identified in all patients, and magnetic resonance-guided biopsy was performed in all CSRs to obtain histopathological verification. For all CSRs, a median ADC (mADC) was calculated. Wilcoxon signed ranks and Mann-Whitney tests was performed to detect differences between the groups. We used the area under the receiver operating characteristic curve to evaluate the accuracy of mADC to predict the presence of PCa in a CSR. Level of statistical significance was set at P < 0.05., Results: Mean mADC in the CSRs with PCa was 1.04 × 10⁻³ mm²/s (SD, 0.29), whereas the CSRs with no PCa displayed a mean mADC of 1.26 × 10⁻³ mm²/s (SD, 0.25; P < 0.001). Cancer-suspicious regions with a high-grade Gleason component displayed a mean mADC of 0.84 × 10⁻³ mm²/s (SD, 0.35) vs a mean mADC for the low-grade CSRs of 1.09 × 10⁻³ mm²/s (SD, 0.25; P < 0.05). A diagnostic accuracy of mADC for predicting the presence of PCa in a CSR with an area under the receiver operating characteristic curve of 0.73 was established (95% confidence interval, 0.61-0.84)., Conclusions: Median ADC is able to predict the presence and grade of PCa in CSRs identified by MP-MRI.

Introduction: Diffusion-weighted magnetic resonance (MR) imaging (DWI) might be able to fulfill the need to accurately identify high-grade prostate carcinoma, in patients initially selected for active surveillance in the Prostate Specific Antigen (PSA) screening era based on transrectal ultrasound-guided biopsy Gleason score. We aimed to determine whether DWI is able to correctly identify those patients with a biopsy Gleason score of ≤ 3 + 3 = 6, but harboring Gleason 4 and/or 5 components in their radical prostatectomy (RP) specimen., Materials and Methods: Whole-mount RP specimens were used to identify regions of interest corresponding with tumor on the DWI-derived apparent diffusion coefficient (ADC) maps in 23 patients with a Gleason ≤ 3 + 3 = 6 on biopsy. ADC values were correlated with RP Gleason grades. Statistical analysis was performed by calculating area under the receiver operating characteristic curve for identification of prostate cancer with Gleason 4 and/or 5 components using DWI, and Mann-Whitney U testing was performed to detect differences in median ADC values for tumors with presence of Gleason grade 4 and/or 5 versus a highest Gleason grade of ≤ 3 on RP., Results: A diagnostic accuracy of median ADC values for identifying patients subject to transrectal ultrasound-guided biopsy undergrading with an area under the receiver operating characteristic curve of 0.88 was established using RP Gleason score as a reference. In patients harboring a Gleason 4 and/or 5 component, the median ADC was 0.86 × 10(-3) mm/s (standard deviation ± 0.21), whereas patients harboring no Gleason 4 and/or 5 component displayed a median ADC of 1.16 × 10(-3) mm/s (standard deviation ± 0.19) for the single tumor slice with the lowest median ADC (P < 0.002)., Conclusions: DWI is able to predict the presence of high-grade tumor in patients with a Gleason ≤ 3 + 3 = 6 on biopsy, providing important information for treatment decisions.

Purpose: The purpose of this study was to compare the diagnostic performance of 3 Tesla, 3-dimensional (3D) magnetic resonance spectroscopic imaging (MRSI) in the localization of prostate cancer (PCa) with and without the use of an endorectal coil (ERC)., Materials and Methods: Our prospective study was approved by the institutional review board, and written informed consent was obtained from all patients. Between October 2004 and January 2006, 18 patients with histologically proven PCa on biopsy and scheduled for radical prostatectomy were included and underwent 3D-MRSI with and without an ERC. The prostate was divided into 14 regions of interest (ROIs). Four readers independently rated (on a 5-point scale) their confidence that cancer was present in each of these ROIs. These findings were correlated with whole-mount prostatectomy specimens. Areas under the receiver-operating characteristic curve were determined. A difference with a P < 0.05 was considered significant., Results: A total of 504 ROIs were rated for the presence and absence of PCa. Localization of PCa with MRSI with the use of an ERC had a significantly higher areas under the receiver-operating characteristic curve (0.68) than MRSI without the use of an ERC (0.63) (P = 0.015)., Conclusion: The use of an ERC in 3D MRSI in localizing PCa at 3 Tesla slightly but significantly increased the localization performance compared with not using an ERC.

Objectives: The objective of this study was to assess the feasibility of the combination of magnetic resonance (MR)-guided biopsy (MRGB) and diagnostic 3T MR imaging in the localization of local recurrence of prostate cancer (PCa) after external beam radiation therapy (EBRT)., Materials and Methods: Twenty-four consecutive men with biochemical failure suspected of local recurrence after initial EBRT were enrolled prospectively in this study. All patients underwent a diagnostic 3T MR examination of the prostate. T2-weighted and dynamic contrast-enhanced MR images (DCE-MRI) were acquired. Two radiologists evaluated the MR images in consensus for tumor suspicious regions (TSRs) for local recurrence. Subsequently, these TSRs were biopsied under MR-guidance and histopathologically evaluated for the presence of recurrent PCa. Descriptive statistical analysis was applied., Results: Tissue sampling was successful in all patients and all TSRs. The positive predictive value on a per patient basis was 75% (15/20) and on a per TSR basis 68% (26/38). The median number of biopsies taken per patient was 3, and the duration of an MRGB session was 31 minutes. No intervention-related complications occurred., Conclusions: The combination of MRGB and diagnostic MR imaging of the prostate was a feasible technique to localize PCa recurrence after EBRT using a low number of cores in a clinically acceptable time.

In a patient suspected of having recurrent prostate cancer after radiation therapy, we demonstrate the feasibility of noninvasive proton magnetic resonance spectroscopic (1H-MRS) imaging of the prostate and a lymph node at 3 T using a matrix of external surface coils. Written informed consent was obtained from the patient. With 1H-MRS imaging, high choline with low citrate signal was observed in the prostate, and in the lymph node a signal of choline-containing compounds was identified. The tissue level of the compounds in the enlarged lymph node was estimated to be 8.1 mmol/kg water. Subsequent histopathological analysis of systematic transrectal ultrasound-guided prostate biopsy and computed tomography-guided biopsy of the lymph node confirmed the presence of prostate cancer in both.

Objectives: We sought to determine the localization accuracy using 3-dimensional (3D) proton magnetic resonance spectroscopic imaging (MRSI) of the entire prostate with a standardized thresholds approach in prostate cancer patients., Materials and Methods: In a prospective study, 32 consecutive patients were examined. Mean age and prostate specific antigen level were 61 years and 7.8 ng/mL, respectively. Median biopsy Gleason score was 6. T2-weighted MRI and 3D MRSI of the entire prostate were performed. Three readers recorded the location of suspicious peripheral zone and central gland cancer nodules on a standardized division of the prostate (14 regions of interest [ROI]) using a standardized thresholds approach. The degree of diagnostic confidence for each ROI was recorded on a 5-point scale. Reconstructed whole-mount section histopathology was the standard of reference. The sensitivity, specificity, positive, and negative predictive value, overall accuracy and interobserver agreement were calculated. Areas under the ROI-based receiver operating characteristic curve (AUC) and diagnostic performance parameters were determined., Results: The standardized thresholds approach had an accuracy of 81% and an AUC of 0.85-0.86 for differentiation between benign and malignant ROIs in the peripheral zone and an accuracy of 87% and an AUC of 0.86-0.91 for this differentiation in the central gland, respectively. Specificities of 81% to 88% were achieved with accompanying sensitivities of 75% to 92% for both peripheral zone and central gland, respectively. Moderate to near-perfect interobserver agreement was demonstrated (kappa=0.42-0.91)., Conclusion: Our data indicate that a standardized zone-specific threshold approach in MRSI of the prostate is able to prospectively differentiate between benign and malignant tissues in the peripheral zone and the central gland with good accuracy and interobserver agreement.

Rationale and Objectives: We sought to explore the feasibility of magnetic resonance imaging (MRI) of the prostate at 3T, with the knowledge of potential drawbacks of MRI at high field strengths., Material and Method: MRI, dynamic MRI, and 1H-MR spectroscopic imaging were performed in 10 patients with prostate cancer on 1.5T and 3T whole-body scanners. Comparable scan protocols were used, and additional high-resolution measurements at 3T were acquired. For both field strengths the signal-to-noise ratio was calculated and image quality was assessed., Result: At 3T the signal-to-noise ratio improved. This resulted in increased spatial MRI resolution, which significantly improved anatomic detail. The increased spectral resolution improved the separation of individual resonances in MRSI. Contrast-enhanced time-concentration curves could be obtained with a doubled temporal resolution., Conclusions: Initial results of endorectal 3T 1H-MR spectroscopic imaging in prostate cancer patients showed potential advantages: the increase in spatial, temporal, and spectral resolution at higher field strength may result in an improved accuracy in delineating and staging prostate cancer.