Background: Radiologists currently subjectively examine multi-parametric magnetic resonance imaging (MP-MRI) to determine prostate tumor aggressiveness using the Prostate Imaging Reporting and Data System scoring system (PI-RADS). Recent studies showed that modified signal to clutter ratio (SCR), tumor volume, and eccentricity (elongation or roundness) of prostate tumors correlated with Gleason score (GS). No previous studies have combined the prostate tumor’s shape, SCR, tumor volume, in order to predict potential tumor aggressiveness and GS. Methods: MP-MRI (T1, T2, diffusion, dynamic contrast-enhanced images) were obtained, resized, translated, and stitched to form spatially registered multi-parametric cubes. Multi-parametric signatures that characterize prostate tumors were inserted into a target detection algorithm [adaptive cosine estimator (ACE)]. Pixel-based blobbing, and labeling were applied to the threshold ACE images. Eccentricity calculation used moments of inertia from the blobs. Tumor volume was computed by counting pixels within multi parametric MRI blobs and tumor outlines based on pathologist assessment of whole mount histology. Pathology assessment of GS was performed on whole mount prostatectomy. The covariance matrix and mean of normal tissue background was computed from normal prostate. Using signatures and normal tissue statistics, the z-score, noise corrected SCR [principal component (PC), modified regularization] from each patient was computed. Eccentricity, tumor volume, and SCR were fitted to GS. Analysis of variance assesses the relationship among the variables. Results: A multivariate analysis generated correlation coefficient (0.60 to 0.784) and P value (0.00741 to <0.0001) from fitting two sets of independent variates, namely, tumor eccentricity (the eccentricity for the largest blob, weighted average for the eccentricity) and SCR (removing 3 PCs, removing 4 PCs, modified regularization, and z-score) to GS. The eccentricity t-statistic exceeded the SCR t-statistic. The three-variable fit to GS using tumor volume (histology, MRI) yielded correlation coefficients ranging from 0.724 to 0.819 (P value <<0.05). Tumor volumes generated from histology yielded higher correlation coefficients than MRI volumes. Adding volume to eccentricity and SCR adds little improvement for fitting GS due to higher correlation coefficients among independent variables and little additional, independent information. Conclusions: Combining prostate tumors eccentricity with SCR relatively highly correlates with GS.

Background: Prostate tumor volume correlates with critical components of cancer staging such as Gleason score (GS) grade, predicted disease progression, and metastasis. Therefore, non-invasive tumor volume measurement may elevate clinical management. Radiology assessments of multi-parametric MRI (MP-MRI) commonly visually examine individual images to determine possible tumor presence. This study combines registered MP-MRI into a single image that display normal tissue and possible lesions. This study tests and exploits the vector nature of spatially registered MP-MRI by using supervised target detection algorithms (STDA) and color display and psychovisual analysis (CIELAB) to non-invasively estimate prostate tumor volume. Methods: MRI, including T1, T2, diffusion [apparent diffusion coefficient (ADC)], dynamic contrast enhanced (DCE) images, were resampled, rescaled, translated, and stitched to form spatially registered Multi-parametric cubes. The multi-parametric or multi-spectral signatures (7-component or T1, T2, ADC, etc.) that characterize the prostate tumors were inserted into target detection algorithms with conical decision surfaces (adaptive cosine estimator, ACE). Various detection thresholds were applied to discriminate tumor from normal tissue. In addition, tumor appeared as yellow in color images that were created by assigning red to washout from DCE, green to high B from diffusion, and blue to autonomous diffusion image. The yellow voxels in the three-channel hypercube were visually identified by a reader and recording voxels that exceed a threshold in the b* component of the CIELAB algorithm. The number of reported tumor voxels were converted to volume based on spatial resolution and slice separation. The tumor volume measurements were quantitatively validated by comparing the tumor volume computations to the pathologist's assessment of the histology of sectioned whole mount prostates from 26 consecutive patients with prostate adenocarcinoma who underwent radical prostatectomy. This study analyzed tumors exceeding 1 cc and that also took up contrast material (18 patients). Results: High correlation coefficients for tumor volume measurements using supervised target detection and color analysis vs. histology from wholemount prostatectomy were computed (R=0.83 and 0.91, respectively). A linear fit for tumor volume measurements using for supervised target detection and color analysis vs. tumor measurements from radical prostatectomy (after correcting for shrinkage from the radical prostatectomy) results in a slope of 1.02 and 3.02, respectively. A polynomial fit for the color analysis to the histology found (R=0.95). Voxels exceeding a threshold in the b* part of the CIELAB algorithm yielded correlation coefficients (0.71, 0.80) offsets (0.01 cc, -0.63 cc) and slopes (1.99, 0.89) against the wholemount prostatectomy and color analysis, respectively. Conclusions: Supervised target detection and color display and analysis applied to registered MP-MRI non-invasively estimates prostate tumor volumes >1 cc and displaying angiogenesis.

Background: Current prostate cancer evaluation can be inaccurate and burdensome. To help non-invasive prostate tumor assessment, recent algorithms applied to spatially registered multi-parametric (SRMP) MRI extracted novel clinically relevant metrics, namely the tumor’s eccentricity (shape), signal-to-clutter ratio (SCR), and volume.Purpose: Conduct a pilot study to predict the risk of developing clinically significant prostate cancer using nomograms and employing Decision Curves Analysis (DCA) from the SRMP MRI-based features to help clinicians non-invasively manage prostate cancer.Methods: This study retrospectively analyzed 25 prostate cancer patients. MP-MRI (T1, T2, diffusion, dynamic contrast-enhanced) were resized, translated, and stitched to form SRMP MRI. Target detection algorithm [adaptive cosine estimator (ACE)] applied to SRMP MRI determines tumor’s eccentricity, noise reduced SCR (by regularizing or eliminating principal components (PC) from the covariance matrix), and volume. Pathology assessed wholemount prostatectomy for Gleason score (GS). Tumors with GS >=4+3 (<=3+4) were judged as “Clinically Significant” (“Insignificant”). Logistic regression combined eccentricity, SCR, volume to generate probability distribution. Nomograms, DCA used all patients plus training (13 patients) and test (12 patients) sets. Area Under the Curves for (AUC) for Receiver Operator Curves (ROC) and p-values evaluated the performance.Results: Combining eccentricity (0.45 ACE threshold), SCR (3, 4 PCs), SCR (regularized, modified regularization) with tumor volume (0.65 ACE threshold) improved AUC (>0.70) for ROC curves and p-values (<0.05) for logistic fit. DCA showed greater net benefit from model fit than univariate analysis, treating “all,” or “none.” Training/test sets achieved comparable AUC but with higher p-values.Conclusions: Performance of nomograms and DCA based on metrics derived from SRMP-MRI in this pilot study were comparable to those using prostate serum antigen, age, and PI-RADS.

Prostate tumor eccentricity predicts Gleason score better than prostate tumor volume Rulon Mayer, Charles B. Simone II, Baris Turkbey, Peter Choyke