Image Guided Focal Therapy for Magnetic Resonance Imaging Visible Prostate Cancer: Defining a 3-Dimensional Treatment Margin Based on Magnetic Resonance Imaging Histology Co-Registration Analysis.

PURPOSE: We compared prostate tumor boundaries on magnetic resonance imaging and radical prostatectomy histological assessment using detailed software assisted co-registration to define an optimal treatment margin for achieving complete tumor destruction during image guided focal ablation. MATERIALS AND METHODS: Included in study were 33 patients who underwent 3 Tesla magnetic resonance imaging before radical prostatectomy. A radiologist traced lesion borders on magnetic resonance imaging and assigned a suspicion score of 2 to 5. Three-dimensional reconstructions were created from high resolution digitalized slides of radical prostatectomy specimens and co-registered to imaging using advanced software. Tumors were compared between histology and imaging by the Hausdorff distance and stratified by the magnetic resonance imaging suspicion score, Gleason score and lesion diameter. Cylindrical volume estimates of treatment effects were used to define the optimal treatment margin. RESULTS: Three-dimensional software based registration with magnetic resonance imaging was done in 46 histologically confirmed cancers. Imaging underestimated tumor size with a maximal discrepancy between imaging and histological boundaries for a given tumor of an average ± SD of 1.99 ± 3.1 mm, representing 18.5% of the diameter on imaging. Boundary underestimation was larger for lesions with an imaging suspicion score 4 or greater (mean 3.49 ± 2.1 mm, p <0.001) and a Gleason score of 7 or greater (mean 2.48 ± 2.8 mm, p = 0.035). A simulated cylindrical treatment volume based on the imaging boundary missed an average 14.8% of tumor volume compared to that based on the histological boundary. A simulated treatment volume based on a 9 mm treatment margin achieved complete histological tumor destruction in 100% of patients. CONCLUSIONS: Magnetic resonance imaging underestimates histologically determined tumor boundaries, especially for lesions with a high imaging suspicion score and a high Gleason score. A 9 mm treatment margin around a lesion visible on magnetic resonance imaging would consistently ensure treatment of the entire histological tumor volume during focal ablative therapy.

T2-weighted prostate MRI at 7 Tesla using a simplified external transmit-receive coil array: correlation with radical prostatectomy findings in two prostate cancer patients.

PURPOSE: To report design of a simplified external transmit-receive coil array for 7 Tesla (T) prostate MRI, including demonstration of the array for tumor localization using T2-weighted imaging (T2WI) at 7T before prostatectomy. MATERIALS AND METHODS: Following simulations of transmitter designs not requiring parallel transmission or radiofrequency-shimming, a coil array was constructed using loop elements, with anterior and posterior rows comprising one transmit-receive element and three receive-only elements. This coil structure was optimized using a whole-body phantom. In vivo sequence optimization was performed to optimize achieved flip angle (FA) and signal to noise ratio (SNR) in prostate. The system was evaluated in a healthy volunteer at 3T and 7T. The 7T T2WI was performed in two prostate cancer patients before prostatectomy, and localization of dominant tumors was subjectively compared with histopathological findings. Image quality was compared between 3T and 7T in these patients. RESULTS: Simulations of the B1(+) field in prostate using two-loop design showed good magnitude (B1(+) of 0.245 A/m/w(1/2)) and uniformity (nonuniformity [SD/mean] of 10.4%). In the volunteer, 90° FA was achieved in prostate using 225 v 1 ms hard-pulse (indicating good efficiency), FA maps confirmed good uniformity (14.1% nonuniformity), and SNR maps showed SNR gain of 2.1 at 7T versus 3T. In patients, 7T T2WI showed excellent visual correspondence with prostatectomy findings. 7T images demonstrated higher estimated SNR (eSNR) in benign peripheral zone (PZ) and tumor compared with 3T, but lower eSNR in fat and slight decreases in tumor-to-PZ contrast and PZ-homogeneity. CONCLUSION: We have demonstrated feasibility of a simplified external coil array for high-resolution T2-weighted prostate MRI at 7T.

Understanding the pathological implications of MRI: application to focal therapy planning.

PURPOSE OF REVIEW: The current challenge in prostate cancer (PCa) focal therapy indication and planning is how to accurately estimate tumor parameters such as volume, extent and grade. In addition to biopsy results, MRI provides an estimation of PCa contour, volume and histopathological characteristics such as presence of high Gleason grade. Among MRI sequences, diffusion-weighted imaging with apparent diffusion coefficient map is the sequence that showed the best results for cancer aggressiveness characterization. RECENT FINDINGS: It was shown that the higher the Gleason score, the lower the apparent diffusion coefficient value. However, accuracy is not sufficient for peripheral zone cancers to be validated for clinical decision and it was not enough investigated for transition zone cancers. Analysis of tumor extent showed a significant underestimation of tumor volume by imaging and this finding should be taken into consideration when planning focal therapy procedures. SUMMARY: Pathological implications of MRI for focal therapy planning are significant but not mature enough to be validated. Future research should aim to quantify cellularity and architectural patterns of PCa Gleason system in correlation with signal abnormalities for better assessment of tumor aggressiveness and extent, and to compare the boundaries of tumors between MRI and histopathological evaluation in order to define an optimal treatment margin.

Optimization of prostate biopsy: the role of magnetic resonance imaging targeted biopsy in detection, localization and risk assessment.

PURPOSE: Optimization of prostate biopsy requires addressing the shortcomings of standard systematic transrectal ultrasound guided biopsy, including false-negative rates, incorrect risk stratification, detection of clinically insignificant disease and the need for repeat biopsy. Magnetic resonance imaging is an evolving noninvasive imaging modality that increases the accurate localization of prostate cancer at the time of biopsy, and thereby enhances clinical risk assessment and improves the ability to appropriately counsel patients regarding therapy. In this review we 1) summarize the various sequences that comprise a prostate multiparametric magnetic resonance imaging examination along with its performance characteristics in cancer detection, localization and reporting standards; 2) evaluate potential applications of magnetic resonance imaging targeting in prostate biopsy among men with no previous biopsy, a negative previous biopsy and those with low stage cancer; and 3) describe the techniques of magnetic resonance imaging targeted biopsy and comparative study outcomes. MATERIALS AND METHODS: A bibliographic search covering the period up to October 2013 was conducted using MEDLINE®/PubMed®. Articles were reviewed and categorized based on which of the 3 objectives of this review was addressed. Data were extracted, analyzed and summarized. RESULTS: Multiparametric magnetic resonance imaging consists of anatomical T2-weighted imaging coupled with at least 2 functional imaging techniques. It has demonstrated improved prostate cancer detection sensitivity up to 80% in the peripheral zone and 81% in the transition zone. A prostate cancer magnetic resonance imaging suspicion score has been developed, and is depicted using the Likert or PI-RADS (Prostate Imaging Reporting and Data System) scale for better standardization of magnetic resonance imaging interpretation and reporting. Among men with no previous biopsy, magnetic resonance imaging increases the frequency of significant cancer detection to 50% in low risk and 71% in high risk patients. In low risk men the negative predictive value of a combination of negative magnetic resonance imaging with prostate volume parameters is nearly 98%, suggesting a potential role in avoiding biopsy and reducing over detection/overtreatment. Among men with a previous negative biopsy 72% to 87% of cancers detected by magnetic resonance imaging guidance are clinically significant. Among men with a known low risk cancer, repeat biopsy using magnetic resonance targeting demonstrates a high likelihood of confirming low risk disease in low suspicion score lesions and of upgrading in high suspicion score lesions. Techniques of magnetic resonance imaging targeted biopsy include visual estimation transrectal ultrasound guided biopsy; software co-registered magnetic resonance imaging-ultrasound, transrectal ultrasound guided biopsy; and in-bore magnetic resonance imaging guided biopsy. Although the improvement in accuracy and efficiency of visual estimation biopsy compared to systematic appears limited, co-registered magnetic resonance imaging-ultrasound biopsy as well as in-bore magnetic resonance imaging guided biopsy appear to increase cancer detection rates in conjunction with increasing suspicion score. CONCLUSIONS: Use of magnetic resonance imaging for targeting prostate biopsies has the potential to reduce the sampling error associated with conventional biopsy by providing better disease localization and sampling. More accurate risk stratification through improved cancer sampling may impact therapeutic decision making. Optimal clinical application of magnetic resonance imaging targeted biopsy remains under investigation.

Prostate tumour volumes: evaluation of the agreement between magnetic resonance imaging and histology using novel co-registration software.

OBJECTIVE: To evaluate the agreement between prostate tumour volume determined using multiparametric magnetic resonance imaging (MRI) and that determined by histological assessment, using detailed software-assisted co-registration. MATERIALS AND METHODS: A total of 37 patients who underwent 3T multiparametric MRI (T2-weighted imaging [T2WI], diffusion-weighted imaging [DWI]/apparent diffusion coefficient [ADC], dynamic contrast-enhanced [DCE] imaging) were included. A radiologist traced the borders of suspicious lesions on T2WI and ADC and assigned a suspicion score of between 2 and 5, while a uropathologist traced the borders of tumours on histopathological photographs. Software was used to co-register MRI and three-dimensional digital reconstructions of radical prostatectomy specimens and to compute imaging and histopathological volumes. Agreement in volumes between MRI and histology was assessed using Bland-Altman plots and stratified by tumour characteristics. RESULTS: Among 50 tumours, the mean differences (95% limits of agreement) in MRI relative to histology were -32% (-128 to +65%) on T2WI and -47% (-143 to +49%) on ADC. For all tumour subsets, volume underestimation was more marked on ADC maps (mean difference ranging from -57 to -16%) than on T2WI (mean difference ranging from -45 to +2%). The 95% limits of agreement were wide for all comparisons, with the lower 95% limit ranging between -77 and -143% across assessments. Volume underestimation was more marked for tumours with a Gleason score ≥7 or a MRI suspicion score 4 or 5. CONCLUSION: Volume estimates of prostate cancer using MRI tended to substantially underestimate histopathological volumes, with a wide variability in extent of underestimation across cases. These findings have implications for efforts to use MRI to guide risk assessment.

Size-adjusted Quantitative Gleason Score as a Predictor of Biochemical Recurrence after Radical Prostatectomy.

BACKGROUND: The risk of biochemical recurrence (BCR) following radical prostatectomy for pathologic Gleason 7 prostate cancer varies according to the proportion of Gleason 4 component. OBJECTIVE: We sought to explore the value of several novel quantitative metrics of Gleason 4 disease for the prediction of BCR in men with Gleason 7 disease. DESIGN, SETTING, AND PARTICIPANTS: We analyzed a cohort of 2630 radical prostatectomy cases from 1990-2007. All pathologic Gleason 7 cases were identified and assessed for quantity of Gleason pattern 4. Three methods were used to quantify the extent of Gleason 4: a quantitative Gleason score (qGS) based on the proportion of tumor composed of Gleason pattern 4, a size-weighted score (swGS) incorporating the overall quantity of Gleason 4, and a size index (siGS) incorporating the quantity of Gleason 4 based on the index lesion. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Associations between the above metrics and BCR were evaluated using Cox proportional hazards regression analysis. RESULTS AND LIMITATIONS: qGS, swGS, and siGS were significantly associated with BCR on multivariate analysis when adjusted for traditional Gleason score, age, prostate specific antigen, surgical margin, and stage. Using Harrell's c-index to compare the scoring systems, qGS (0.83), swGS (0.84), and siGS (0.84) all performed better than the traditional Gleason score (0.82). CONCLUSIONS: Quantitative measures of Gleason pattern 4 predict BCR better than the traditional Gleason score. PATIENT SUMMARY: In men with Gleason 7 prostate cancer, quantitative analysis of the proportion of Gleason pattern 4 (quantitative Gleason score), as well as size-weighted measurement of Gleason 4 (size-weighted Gleason score), and a size-weighted measurement of Gleason 4 based on the largest tumor nodule significantly improve the predicted risk of biochemical recurrence compared with the traditional Gleason score.