The Potential of Iron Oxide Nanoparticle-Enhanced MRI at 7 T Compared With 3 T for Detecting Small Suspicious Lymph Nodes in Patients With Prostate Cancer.

BACKGROUND: Accurate detection of lymph node (LN) metastases in prostate cancer (PCa) is a challenging but crucial step for disease staging. Ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) enables distinction between healthy LNs and nodes suspicious for harboring metastases. When combined with MRI at an ultra-high magnetic field, an unprecedented spatial resolution can be exploited to visualize these LNs. PURPOSE: The aim of this study was to explore USPIO-enhanced MRI at 7 T in comparison to 3 T for the detection of small suspicious LNs in the same cohort of patients with PCa. MATERIALS AND METHODS: Twenty PCa patients with high-risk primary or recurrent disease were referred to our hospital for an investigational USPIO-enhanced 3 T MRI examination with ferumoxtran-10. With consent, they underwent a 7 T MRI on the same day. Three-dimensional anatomical and T2*-weighted images of both examinations were evaluated blinded, with an interval, by 2 readers who annotated LNs suspicious for metastases. Number, size, and level of suspicion (LoS) of LNs were paired within patients and compared between field strengths. RESULTS: At 7 T, both readers annotated significantly more LNs compared with 3 T (474 and 284 vs 344 and 162), with 116 suspicious LNs on 7 T (range, 1-34 per patient) and 79 suspicious LNs on 3 T (range, 1-14 per patient) in 17 patients. For suspicious LNs, the median short axis diameter was 2.6 mm on 7 T (1.3-9.5 mm) and 2.8 mm for 3 T (1.7-10.4 mm, P = 0.05), with large overlap in short axis of annotated LNs between LoS groups. At 7 T, significantly more suspicious LNs had a short axis <2.5 mm compared with 3 T (44% vs 27%). Magnetic resonance imaging at 7 T provided better image quality and structure delineation and a higher LoS score for suspicious nodes. CONCLUSIONS: In the same cohort of patients with PCa, more and more small LNs were detected on 7 T USPIO-enhanced MRI compared with 3 T MRI. Suspicious LNs are generally very small, and increased nodal size was not a good indication of suspicion for the presence of metastases. The high spatial resolution of USPIO-enhanced MRI at 7 T improves structure delineation and the visibility of very small suspicious LNs, potentially expanding the in vivo detection limits of pelvic LN metastases in PCa patients.

Ferumoxtran-10-enhanced 3-T Magnetic Resonance Angiography of Pelvic Arteries: Initial Experience.

BACKGROUND: Patients with renal impairment cannot undergo angiography because iodine and gadolinium contrast agents are contraindicated. Iron-containing ultrasmall superparamagnetic iron oxide particles, such as ferumoxtran-10, are not contraindicated in these patients. Thus, patients with renal failure can still undergo angiography with ferumoxtran-10. OBJECTIVE: To evaluate the visibility of pelvic vessels with magnetic resonance angiography (MRA) using ferumoxtran-10 as contrast agent. DESIGN, SETTING, AND PARTICIPANTS: Three hundred and eighty-one patients diagnosed with primary or recurrent prostate cancer underwent pelvic ferumoxtran-10 MRA. Eleven anatomical pelvic-vessel segments per patient were evaluated using qualitative and quantitative criteria for image quality (IQ), vessel visibility (VV), and the contrast-to-noise ratio (CNR). INTERVENTION: Ferumoxtran-10-enhaced MRA. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: IQ, VV, and CNR were assessed on a 5-point scale for each data set/vessel segment (very poor, poor, moderate, good, and excellent). RESULTS AND LIMITATIONS: IQ was good to excellent for 98.2% of the data sets and VV was good to excellent for 97.7% of all vessel segments. The mean CNR for all segments was 88.13 (standard deviation 4.22). Contrast bolus imaging cannot be performed with this technique, so it is impossible to visualize the arterial or venous phase separately. The timing of contrast administration is also a limitation, with MRA performed 1 d after contrast infusion. CONCLUSIONS: Ferumoxtran-10 MRA showed excellent image quality and visibility for pelvic vessels. In addition, the homogeneity of the intraluminal contrast was superior. Patients with preterminal or terminal renal function can benefit from ferumoxtran-10 MRA if visualization of their pelvic vessels is required. PATIENT SUMMARY: Magnetic resonance imaging of blood vessels using a contrast agent called ferumoxtran-10 is a promising technique for patients with impaired kidney function, as it provides high-quality visualization of blood vessels in the pelvis.

Genomic Evaluation of Multiparametric Magnetic Resonance Imaging-visible and -nonvisible Lesions in Clinically Localised Prostate Cancer.

BACKGROUND: The prostate cancer (PCa) diagnostic pathway is undergoing a radical change with the introduction of multiparametric magnetic resonance imaging (mpMRI), genomic testing, and different prostate biopsy techniques. It has been proposed that these tests should be used in a sequential manner to optimise risk stratification. OBJECTIVE: To characterise the genomic, epigenomic, and transcriptomic features of mpMRI-visible and -nonvisible PCa in clinically localised disease. DESIGN, SETTING, AND PARTICIPANTS: Multicore analysis of fresh prostate tissue sampled immediately after radical prostatectomy was performed for intermediate- to high-risk PCa. INTERVENTION: Low-pass whole-genome, exome, methylation, and transcriptome profiling of patient tissue cores taken from microscopically benign and cancerous areas in the same prostate. Circulating free and germline DNA was assessed from the blood of five patients. OUTCOME MEASUREMENT AND STATISTICAL ANALYSIS: Correlations between preoperative mpMRI and genomic characteristics of tumour and benign prostate samples were assessed. Gene profiles for individual tumour cores were correlated with existing genomic classifiers currently used for prognostication. RESULTS AND LIMITATIONS: A total of 43 prostate cores (22 tumour and 21 benign) were profiled from six whole prostate glands. Of the 22 tumour cores, 16 were tumours visible and six were tumours nonvisible on mpMRI. Intratumour genomic, epigenomic, and transcriptomic heterogeneity was found within mpMRI-visible lesions. This could potentially lead to misclassification of patients using signatures based on copy number or RNA expression. Moreover, three of the six cores obtained from mpMRI-nonvisible tumours harboured one or more genetic alterations commonly observed in metastatic castration-resistant PCa. No circulating free DNA alterations were found. Limitations include the small cohort size and lack of follow-up. CONCLUSIONS: Our study supports the continued use of systematic prostate sampling in addition to mpMRI, as avoidance of systematic biopsies in patients with negative mpMRI may mean that clinically significant tumours harbouring genetic alterations commonly seen in metastatic PCa are missed. Furthermore, there is inconsistency in individual genomics when genomic classifiers are applied. PATIENT SUMMARY: Our study shows that tumour heterogeneity within prostate tumours visible on multiparametric magnetic resonance imaging (mpMRI) can lead to misclassification of patients if only one core is used for genomic analysis. In addition, some cancers that were missed by mpMRI had genomic aberrations that are commonly seen in advanced metastatic prostate cancer. Avoiding biopsies in mpMRI-negative cases may mean that such potentially lethal cancers are missed.

Intranodal signal suppression in pelvic MR lymphography of prostate cancer patients: a quantitative comparison of ferumoxtran-10 and ferumoxytol.

OBJECTIVES: The key to MR lymphography is suppression of T2* MR signal in normal lymph nodes, while retaining high signal in metastatic nodes. Our objective is to quantitatively compare the ability of ferumoxtran-10 and ferumoxytol to suppress the MR signal in normal pelvic lymph nodes. METHODS: In 2010, a set of consecutive patients who underwent intravenous MR Lymphography (MRL) were included. Signal suppression in normal lymph nodes in T2*-weighted images due to uptake of USPIO (Ultra-Small Superparamagnetic Particles of Iron Oxide) was quantified. Signal suppression by two USPIO contrast agents, ferumoxtran-10 and ferumoxytol was compared using Wilcoxon's signed rank test. RESULTS: Forty-four patients were included, of which all 44 had a ferumoxtran-10 MRL and 4 had additionally a ferumoxytol MRL. A total of 684 lymph nodes were identified in the images, of which 174 had been diagnosed as metastatic. USPIO-induced signal suppression in normal lymph nodes was significantly stronger in ferumoxtran-10 MRL than in ferumoxytol MRL (p < 0.005). CONCLUSIONS: T2* signal suppression in normal pelvic lymph nodes is significantly stronger with ferumoxtran-10 than with ferumoxytol, which may affect diagnostic accuracy.

Contribution of Histopathologic Tissue Composition to Quantitative MR Spectroscopy and Diffusion-weighted Imaging of the Prostate.

PURPOSE: To determine associations of metabolite levels derived from magnetic resonance (MR) spectroscopic imaging (ie, hydrogen 1 [(1)H] MR spectroscopic imaging) and apparent diffusion coefficients (ADCs) from diffusion-weighted imaging with prostate tissue composition assessed by digital image analysis of histologic sections. MATERIALS AND METHODS: Institutional ethical review board approved this retrospective study and waived informed consent. Fifty-seven prostate cancer patients underwent an MR examination followed by prostatectomy. One hematoxylin and eosin-stained section of the resected prostate per patient was digitized and computationally segmented into nuclei, lumen, and combination of epithelial cytoplasm and stroma. On each stained section, regions of interest (ROIs) were chosen and matched to the corresponding ADC map and (1)H MR spectroscopic imaging voxels. ADC and two metabolite ratios (citrate [Cit], spermine [Spm], and creatine [Cr] to choline [Cho] and Cho to Cr plus Spm) were correlated with percentage areas of nuclei, lumen, and cytoplasm and stroma for peripheral zone (PZ), transition zone (TZ), and tumor tissue in both zones of the prostate by using a linear mixed-effect model and Spearman correlation coefficient (ρ). RESULTS: ADC and (Cit + Spm + Cr)/Cho ratio showed positive correlation with percentage area of lumen (ρ = 0.43 and 0.50, respectively) and negative correlation with percentage area of nuclei (ρ = -0.29 and -0.26, respectively). The Cho/(Cr + Spm) ratio showed negative association with percentage area of lumen (ρ = -0.40) and positive association with area of nuclei (ρ = 0.26). Percentage areas of lumen and nuclei, (Cit + Spm + Cr)/Cho ratio, and ADC were significantly different (P < .001) between benign PZ (23.7 and 7.7, 8.83, and 1.58 × 10(-3) mm(2)/sec, respectively) and tumor PZ tissue (11.4 and 12.5, 5.13, and 1.20 × 10(-3) mm(2)/sec, respectively). These parameters were also significantly different between benign TZ (20.0 and 8.2, 6.50, and 1.26 × 10(-3) mm(2)/sec, respectively) and tumor TZ tissue (9.8 and 11.2, 4.36, and 1.03 × 10(-3) mm(2)/sec, respectively). CONCLUSION: The observed correlation of (Cit + Spm + Cr)/Cho ratio and ADC of the prostate with its tissue composition indicates that components of this composition, such as percentage luminal area, contribute to the value of these MR parameters.

Multiparametric Magnetic Resonance Imaging for Discriminating Low-Grade From High-Grade Prostate Cancer.

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.

Correlation between dynamic contrast-enhanced MRI and quantitative histopathologic microvascular parameters in organ-confined prostate cancer.

OBJECTIVES: To correlate pharmacokinetic parameters of 3-T dynamic contrast-enhanced (DCE-)MRI with histopathologic microvascular and lymphatic parameters in organ-confined prostate cancer. METHODS: In 18 patients with unilateral peripheral zone (pT2a) tumours who underwent DCE-MRI prior to radical prostatectomy (RP), the following pharmacokinetic parameters were assessed: permeability surface area volume transfer constant (K (trans)), extravascular extracellular volume (Ve) and rate constant (K ep). In the RP sections blood and lymph vessels were visualised immunohistochemically and automatically examined and analysed. Parameters assessed included microvessel density (MVD), area (MVA) and perimeter (MVP) as well as lymph vessel density (LVD), area (LVA) and perimeter (LVP). RESULTS: A negative correlation was found between age and K (trans) and K ep for tumour (r = -0.60, p = 0.009; r = -0.67, p = 0.002) and normal (r = -0.54, p = 0.021; r = -0.46, p = 0.055) tissue. No correlation existed between absolute values of microvascular parameters from histopathology and DCE-MRI. In contrast, the ratio between tumour and normal tissue (correcting for individual microvascularity variations) significantly correlated between K ep and MVD (r = 0.61, p = 0.007) and MVP (r = 0.54, p = 0.022). The lymphovascular parameters showed only a correlation between LVA and K ep (r = -0.66, p = 0.003). CONCLUSIONS: Significant correlations between DCE-MRI and histopathologic parameters were found when correcting for interpatient variations in microvascularity. KEY POINTS: • Normal prostate tissue shows strong heterogeneity in microvascularity. • Peripheral zone prostate cancer shows increased and less heterogeneous microvascularity. • Normal and tumour tissue shows considerable variation in microvascularity between patients. • DCE-MRI should take into account the interprostatic heterogeneity of microvasculature between patients.

Value of 3-T multiparametric magnetic resonance imaging and magnetic resonance-guided biopsy for early risk restratification in active surveillance of low-risk prostate cancer: a prospective multicenter cohort study.

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.

Assessment of prostate cancer aggressiveness using dynamic contrast-enhanced magnetic resonance imaging at 3 T.

BACKGROUND: A challenge in the diagnosis of prostate cancer (PCa) is the accurate assessment of aggressiveness. OBJECTIVE: To validate the performance of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) of the prostate at 3 tesla (T) for the assessment of PCa aggressiveness, with prostatectomy specimens as the reference standard. DESIGN, SETTINGS, AND PARTICIPANTS: A total of 45 patients with PCa scheduled for prostatectomy were included. This study was approved by the institutional review board; the need for informed consent was waived. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Subjects underwent a clinical MRI protocol including DCE-MRI. Blinded to DCE-images, PCa was indicated on T2-weighted images based on histopathology results from prostatectomy specimens with the use of anatomical landmarks for the precise localization of the tumor. PCa was classified as low-, intermediate-, or high-grade, according to Gleason score. DCE-images were used as an overlay on T2-weighted images; mean and quartile values from semi-quantitative and pharmacokinetic model parameters were extracted per tumor region. Statistical analysis included Spearman's ρ, the Kruskal-Wallis test, and a receiver operating characteristics (ROC) analysis. RESULTS AND LIMITATIONS: Significant differences were seen for the mean and 75th percentile (p75) values of wash-in (p = 0.024 and p = 0.017, respectively), mean wash-out (p = 0.044), and p75 of transfer constant (K(trans)) (p = 0.035), all between low-grade and high-grade PCa in the peripheral zone. ROC analysis revealed the best discriminating performance between low-grade versus intermediate-grade plus high-grade PCa in the peripheral zone for p75 of wash-in, K(trans), and rate constant (Kep) (area under the curve: 0.72). Due to a limited number of tumors in the transition zone, a definitive conclusion for this region of the prostate could not be drawn. CONCLUSIONS: Quantitative parameters (K(trans) and Kep) and semi-quantitative parameters (wash-in and wash-out) derived from DCE-MRI at 3 T have the potential to assess the aggressiveness of PCa in the peripheral zone. P75 of wash-in, K(trans), and Kep offer the best possibility to discriminate low-grade from intermediate-grade plus high-grade PCa.

Evaluation of diffusion-weighted MR imaging at inclusion in an active surveillance protocol for low-risk prostate cancer.

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.

Differentiation of prostatitis and prostate cancer by using diffusion-weighted MR imaging and MR-guided biopsy at 3 T.

PURPOSE: To determine if prostatitis and prostate cancer (PCa) can be distinguished by using apparent diffusion coefficients (ADCs) on magnetic resonance (MR) images, with specimens obtained at MR-guided biopsy as the standard of reference. MATERIALS AND METHODS: The need for institutional review board approval and informed consent was waived. MR-guided biopsies were performed in 130 consecutive patients with cancer-suspicious regions (CSRs) on multiparametric MR images obtained at 3 T. In this retrospective study, 88 patients met the inclusion criteria. During the biopsy procedure, an axial diffusion-weighted sequence was performed and ADC maps were generated (repetition time msec/echo time msec, 2000/67; section thickness, 4 mm; in-plane resolution, 1.8 × 1.8 mm; and b values of 0, 100, 500, and 800 sec/mm(2)). Subsequently, a confirmation image with the needle left in situ was acquired and projected on the ADC map. The corresponding ADCs at the biopsy location were compared with the histopathologic outcomes of the biopsy specimens. Linear mixed-model regression analyses were used to test for ADC differences between the histopathologic groups. RESULTS: The study included 116 biopsy specimens. Median ADCs of normal prostate tissue, prostatitis, low-grade PCa (Gleason grade components 2 or 3), and high-grade PCa (Gleason grade components 4 or 5) were 1.22 × 10(-3) mm(2)/sec (standard deviation, ± 0.21), 1.08 × 10(-3) mm(2)/sec (± 0.18), 0.88 × 10(-3) mm(2)/sec (± 0.15), and 0.88 × 10(-3) mm(2)/sec (± 0.13), respectively. Although the median ADCs of biopsy specimens with prostatitis were significantly higher compared with low- and high-grade PCa (P < .001), there is a considerable overlap between the tissue types. CONCLUSION: Diffusion-weighted imaging is a noninvasive technique that shows differences between prostatitis and PCa in both the peripheral zone and central gland, although its usability in clinical practice is limited as a result of significant overlap in ADCs.

Transition zone prostate cancer: detection and localization with 3-T multiparametric MR imaging.

PURPOSE: To retrospectively compare transition zone (TZ) cancer detection and localization accuracy of 3-T T2-weighted magnetic resonance (MR) imaging with that of multiparametric (MP) MR imaging, with radical prostatectomy specimens as the reference standard. MATERIALS AND METHODS: The informed consent requirement was waived by the institutional review board. Inclusion criteria were radical prostatectomy specimen TZ cancer larger than 0.5 cm(3) and 3-T endorectal presurgery MP MR imaging (T2-weighted imaging, diffusion-weighted [DW] imaging apparent diffusion coefficient [ADC] maps [b < 1000 sec/mm(2)], and dynamic contrast material-enhanced [DCE] MR imaging). From 197 patients with radical prostatectomy specimens, 28 patients with TZ cancer were included. Thirty-five patients without TZ cancer were randomly selected as a control group. Four radiologists randomly scored T2-weighted and DW ADC images, T2-weighted and DCE MR images, and T2-weighted, DW ADC, and DCE MR images. TZ cancer suspicion was rated on a five-point scale in six TZ regions of interest (ROIs). A score of 4-5 was considered a positive finding. A score of 4 or higher for any ROI containing TZ cancer was considered a positive detection result at the patient level. Generalized estimating equations were used to analyze detection and localization accuracy by using ROI-receiver operating characteristics (ROC) curve analyses for the latter. Gleason grade (GG) 4-5 and GG 2-3 cancers were analyzed separately. RESULTS: Detection accuracy did not differ between T2-weighted and MP MR imaging for all TZ cancers (68% vs 66%, P = .85), GG 4-5 TZ cancers (79% vs 72%-75%, P = .13), and GG 2-3 TZ cancers (66% vs 62%-65%, P = .47). MP MR imaging (area under the ROC curve, 0.70-0.77) did not improve T2-weighted imaging localization accuracy (AUC = 0.72) (P > .05). CONCLUSION: Use of 3-T MP MR imaging, consisting of T2-weighted imaging, DW imaging ADC maps (b values, 50, 500, and 800 sec/mm(2)), and DCE MR imaging may not improve TZ cancer detection and localization accuracy compared with T2-weighted imaging. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120281/-/DC1.

Simulated required accuracy of image registration tools for targeting high-grade cancer components with prostate biopsies.

OBJECTIVES: To estimate the required spatial alignment accuracy for correctly grading 95 % of peripheral zone (PZ) prostate cancers using a system for multiparametric magnetic resonance (MR)-guided ultrasound (US) biopsies. METHODS: PZ prostate tumours were retrospectively annotated on multiparametric MR series using prostatectomy specimens as reference standard. Tumours were grouped based on homogeneous and heterogeneous apparent diffusion coefficient (ADC) values using an automated ADC texture analysis method. The proportion of heterogeneous tumours containing a distinct, high Gleason grade tumour focus yielding low ADC values was determined. Both overall tumour and high-grade focal volumes were calculated. All high-grade target volumes were then used in a simulated US biopsy system with adjustable accuracy to determine the hit rate. RESULTS: An ADC-determined high-grade tumour focus was found in 63 % of the PZ prostate tumours. The focal volumes were significantly smaller than the total tumour volumes (median volume of 0.3 ml and 1.1 ml respectively). To correctly grade 95 % of the aggressive tumour components the target registration error (TRE) should be smaller than 1.9 mm. CONCLUSIONS: To enable finding the high Gleason grade component in 95 % of PZ prostate tumours with MR-guided US biopsies, a technical registration accuracy of 1.9 mm is required. KEY POINTS: • MRI can identify foci of prostatic cancer with reduced apparent diffusion coefficients • Sixty-three per cent of prostatic peripheral zone tumours contain high-grade tumour low ADC foci • The median volume of such foci is 0.3 ml • Biopsy targets are significantly smaller than whole tumour volumes • Simulated registration accuracy is 1.9 mm for correctly grading 95 % of tumours.

Prostate cancer: computer-aided diagnosis with multiparametric 3-T MR imaging--effect on observer performance.

PURPOSE: To determine the effect of computer-aided diagnosis (CAD) on less-experienced and experienced observer performance in differentiation of benign from malignant prostate lesions at 3-T multiparametric magnetic resonance (MR) imaging. MATERIALS AND METHODS: The institutional review board waived the need for informed consent. Retrospectively, 34 patients were included who had prostate cancer and had undergone multiparametric MR imaging, including T2-weighted, diffusion-weighted, and dynamic contrast material-enhanced MR imaging prior to radical prostatectomy. Six radiologists less experienced in prostate imaging and four radiologists experienced in prostate imaging were asked to characterize different regions suspicious for cancer as benign or malignant on multiparametric MR images first without and subsequently with CAD software. The effect of CAD was analyzed by using a multiple-reader, multicase, receiver operating characteristic analysis and a linear mixed-model analysis. RESULTS: In 34 patients, 206 preannotated regions, including 67 malignant and 64 benign regions in the peripheral zone (PZ) and 19 malignant and 56 benign regions in the transition zone (TZ), were evaluated. Stand-alone CAD had an overall area under the receiver operating characteristic curve (AUC) of 0.90. For PZ and TZ lesions, the AUCs were 0.92 and 0.87, respectively. Without CAD, less-experienced observers had an overall AUC of 0.81, which significantly increased to 0.91 (P = .001) with CAD. For experienced observers, the AUC without CAD was 0.88, which increased to 0.91 (P = .17) with CAD. For PZ lesions, less-experienced observers increased their AUC from 0.86 to 0.95 (P < .001) with CAD. Experienced observers showed an increase from 0.91 to 0.93 (P = .13). For TZ lesions, less-experienced observers significantly increased their performance from 0.72 to 0.79 (P = .01) with CAD and experienced observers increased their performance from 0.81 to 0.82 (P = .42). CONCLUSION: Addition of CAD significantly improved the performance of less-experienced observers in distinguishing benign from malignant lesions; when less-experienced observers used CAD, they reached similar performance as experienced observers. The stand-alone performance of CAD was similar to performance of experienced observers.

Interpatient variation in normal peripheral zone apparent diffusion coefficient: effect on the prediction of prostate cancer aggressiveness.

PURPOSE: To determine the interpatient variability of prostate peripheral zone (PZ) apparent diffusion coefficient (ADC) and its effect on the assessment of prostate cancer aggressiveness. MATERIALS AND METHODS: The requirement for institutional review board approval was waived. Intra- and interpatient variation of PZ ADCs was determined by means of repeated measurements of normal ADCs at three magnetic resonance (MR) examinations in a retrospective cohort of 10 consecutive patients who had high prostate-specific antigen levels and negative findings at transrectal ultrasonographically-guided biopsy. In these patients, no signs of PZ cancer were found at all three MR imaging sessions. The effect of interpatient variation on the assessment of prostate cancer aggressiveness was examined in a second retrospective cohort of 51 patients with PZ prostate cancer. Whole-mount step-section pathologic evaluation served as reference standard for placement of regions of interest on tumors and normal PZ. Repeated-measures analysis of variance was used to determine the significance of the interpatient variations in ADCs. Linear logistic regression was used to assess whether incorporating normal PZ ADCs improves the prediction of cancer aggressiveness. RESULTS: Analysis of variance revealed that interpatient variability (1.2-2.0×10(-3) mm2/sec) was significantly larger than measurement variability (0.068×10(-3) mm2/sec±0.027 [standard deviation]) (P=.0058). Stand-alone tumor ADCs showed an area under the receiver operating characteristic curve (AUC) of 0.91 for discriminating low-grade versus high-grade tumors. Incorporating normal PZ ADC significantly improved the AUC to 0.96 (P=.0401). CONCLUSION: PZ ADCs show significant interpatient variation, which has a substantial effect on the prediction of prostate cancer aggressiveness. Correcting this effect results in a significant increase in diagnostic accuracy.

Prostate cancer aggressiveness: in vivo assessment of MR spectroscopy and diffusion-weighted imaging at 3 T.

PURPOSE: To determine the individual and combined performance of magnetic resonance (MR) spectroscopic imaging and diffusion-weighted (DW) imaging at 3 T in the in vivo assessment of prostate cancer aggressiveness by using histopathologically defined regions of interest on radical prostatectomy specimens to define the prostate cancer regions to be investigated. MATERIALS AND METHODS: The local institutional ethics review board approved this retrospective study and waived the informed consent requirement. Fifty-four patients with biopsy-proved prostate cancer underwent clinical MR spectroscopic imaging followed by prostatectomy. Guided by the histopathologic map, all spectroscopy voxels that contained tumor tissue were selected, and metabolite ratios (choline [Cho] plus creatine [Cr]-to-citrate [Cit] and Cho/Cr ratios) were derived. For each spectroscopic voxel, 25th percentile apparent diffusion coefficient (ADC) of the region corresponding to that voxel was determined, representing the most aberrant tumor part on the ADC map, which was often smaller than spectroscopic imaging voxels. Maximum metabolic ratios and minimum 25th percentile ADC of each tumor were related to tumor aggressiveness and were used to differentiate aggressiveness classes. A logistic regression model (LRM) was used to combine data from both modalities. RESULTS: Significant correlation was found between aggressiveness classes and maximum Cho+Cr/Cit ratio (ρ=0.36), maximum Cho/Cr ratio (ρ=0.35), and minimum 25th percentile ADC (ρ=-0.63) in the peripheral zone (PZ). In the transition zone (TZ), the correlation was significant for only Cho+Cr/Cit and Cho/Cr ratios (ρ=0.58 and ρ=0.60, respectively). For differentiation between aggressiveness classes, LRM use did not result in significantly improved differentiation over any individual variables. CONCLUSION: These findings enabled confirmation that MR spectroscopic imaging and DW imaging offer potential for in vivo noninvasive assessment of prostate cancer aggressiveness, and both modalities have comparable performance. The combination did not result in better performance. Nonetheless, the better performances of metabolite ratios in the TZ and of ADCs in the PZ suggest that they have complementary value.

Initial experience with identifying high-grade prostate cancer using diffusion-weighted MR imaging (DWI) in patients with a Gleason score ≤ 3 + 3 = 6 upon schematic TRUS-guided biopsy: a radical prostatectomy correlated series.

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.

Three-Tesla magnetic resonance-guided prostate biopsy in men with increased prostate-specific antigen and repeated, negative, random, systematic, transrectal ultrasound biopsies: detection of clinically significant prostate cancers.

BACKGROUND: Patients with elevated prostate-specific antigen (PSA) and one or more previous negative transrectal ultrasound (TRUS) biopsy sessions are subject to diagnostic uncertainty due to TRUS-biopsy undersampling. Magnetic resonance (MR)-guided biopsy (MRGB) has shown high prostate cancer (PCa)-detection rates in studies with limited patient numbers. OBJECTIVE: Determine the detection rate of (clinically significant) PCa for MRGB of cancer-suspicious regions (CSRs) on 3-T multiparametric MR imaging (MP-MRI) in patients with elevated PSA and one or more negative TRUS-biopsy sessions. DESIGN, SETTING, AND PARTICIPANTS: Of 844 patients who underwent 3-T MP-MRI in our referral centre between March 2008 and February 2011, 438 consecutive patients with a PSA >4.0 ng/ml and one negative TRUS-biopsy session or more were included. MRGB was performed in 265 patients. Exclusion criteria were existent PCa, endorectal coil use, and MP-MRI for indications other than cancer detection. INTERVENTION: Patients underwent MRGB of MP-MRI CSRs. MEASUREMENTS: (Clinically significant) MRGB cancer-detection rates were determined. Clinically significant cancer was defined by accepted (i.a. Epstein and d'Amico) criteria based on PSA, Gleason score, stage, and tumour volume. Follow-up PSA and histopathology were collected. Sensitivity analysis was performed for patients with MP-MRI CSRs without MRGB. RESULTS AND LIMITATIONS: In a total of 117 patients, cancer was detected with MRGB (n=108) or after negative MRGB (n=9). PCa was detected in 108 of 438 patients (25%) and in 41% (108 of 265) of MRGB patients. The majority of detected cancers (87%) were clinically significant. Clinically significant cancers were detected in seven of nine (78%) negative MRGB patients in whom PCa was detected during follow-up. Sensitivity analysis resulted in increased cancer detection (47-56%). Complications occurred in 0.2% of patients (5 of 265). CONCLUSIONS: In patients with elevated PSA and one or more negative TRUS-biopsy sessions, MRGB of MP-MRI CSRs had a PCa-detection rate of 41%. The majority of detected cancers were clinically significant (87%).

Prospective assessment of prostate cancer aggressiveness using 3-T diffusion-weighted magnetic resonance imaging-guided biopsies versus a systematic 10-core transrectal ultrasound prostate biopsy cohort.

BACKGROUND: Accurate pretreatment assessment of prostate cancer (PCa) aggressiveness is important in decision making. Gleason grade is a critical predictor of the aggressiveness of PCa. Transrectal ultrasound-guided biopsies (TRUSBxs) show substantial undergrading of Gleason grades found after radical prostatectomy (RP). Diffusion-weighted magnetic resonance imaging (MRI) has been shown to be a biomarker of tumour aggressiveness. OBJECTIVE: To improve pretreatment assessment of PCa aggressiveness, this study prospectively evaluated MRI-guided prostate biopsies (MR-GBs) of abnormalities determined on diffusion-weighted imaging (DWI) apparent diffusion coefficient (ADC) maps. The results were compared with a 10-core TRUSBx cohort. RP findings served as the gold standard. DESIGN, SETTING, AND PARTICIPANTS: A 10-core TRUSBx (n=64) or MR-GB (n=34) was used for PCa diagnosis before RP in 98 patients. MEASUREMENTS: Using multiparametric 3-T MRI: T2-weighted, dynamic contrast-enhanced imaging, and DWI were performed to identify tumour-suspicious regions in patients with a negative TRUSBx. The regions with the highest restriction on ADC maps within the suspicions regions were used to direct MR-GB. A 10-core TRUSBx was used in a matched cohort. Following RP, the highest Gleason grades (HGGs) in biopsies and RP specimens were identified. Biopsy and RP Gleason grade results were evaluated using chi-square analysis. RESULTS AND LIMITATIONS: No significant differences on RP were observed for proportions of patients having a HGG of 3 (35% vs 28%; p=0.50), 4 (32% vs 41%; p=0.51), and 5 (32% vs 31%; p=0.61) for the MR-GB and TRUSBx cohort, respectively. MR-GB showed an exact performance with RP for overall HGG: 88% (30 of 34); for TRUS-GB it was 55% (35 of 64; p=0.001). In the MR-GB cohort, an exact performance with HGG 3 was 100% (12 of 12); for HGG 4, 91% (10 of 11); and for HGG 5, 73% (8 of 11). The corresponding performance rates for TRUSBx were 94% (17 of 18; p=0.41), 46% (12 of 26; p=0.02), and 30% (6 of 20; p=0.01), respectively. CONCLUSIONS: This study shows prospectively that DWI-directed MR-GBs significantly improve pretreatment risk stratification by obtaining biopsies that are representative of true Gleason grade.