Rulon Mayer

Background/Objectives: Deciding between active surveillance and treatment for prostate cancer patients often requires accurate risk assessment of prostate tumors detected with multi-parametric MRI. Conventionally, radiologists visually inspect MRI and use scoring procedures such as PI-RADS to help assess the scans. More recently, artificial intelligence (AI) applied to MRI has allowed for supplementation and is complementary to clinical assessment. However, AI is computationally expensive and severely saps scarce energy and water resources and requires special processing components, requiring alternate approaches that require less computation and fewer resources. The novel, simpler spectral/statistics approach that mimics color vision was previously successfully applied in a number of retrospective pilot studies of bi-parametric MRI of prostate cancer. The novel approach needs far fewer resources, is less computationally intensive, and is simpler than artificial intelligence to evaluate prostate tumors. However, these earlier spectral/statistics pilot studies required intervention by an analyst and too much time for implementation in future large patient studies that are needed to validate the novel approach. This retrospective pilot study further developed, applied, and tested new automation tools to expedite simpler spectral statistical techniques that need fewer resources to evaluate prostate tumors on multi-parametric MRI. Methods: Automated spatial registration, automated prostate organ segmentation, automated blob generation and selection for spectral signatures derived from the apparent diffusion coefficient, high-B-value DWI, and T2 MRI were performed on 76 consecutive patients in the PI-CAI cohort in this retrospective pilot study. The signal-to-clutter ratio (SCR) was computed using target signatures and the processed statistical metrics of the registered prostate bi-parametric MRI. The processed SCR, spectral/spatial features of blobs and clinical metrics predict clinically significant prostate cancer using multivariate logistic regression. The proposed method was assessed using the area under the curve (AUC) from the receiver operating characteristic curve. Results: AUC values of >0.90 were achieved by combining the SCR with blob and clinical metrics. Increasing the number of non-congruent, independent variables resulted in higher AUC scores. Restricting analysis to blob volumes > 0.1 cm³ achieved higher AUC values. The additional total savings in time by applying the new automation tools reduced the processing time by 80 to 170 min for 10 patients. Implementing the new automation tools resulted in an overall processing time of 40 to 80 min per 10 patients. Conclusions: Automating the spectral/statistics approach resulted in AUCs not inferior to those obtained from AI. The automation achieved sufficiently high AUCs and also reduced processing times, warranting future assessments in large patient cohorts.

Background: Prostate cancer management optimally requires non-invasive, objective, quantitative, accurate evaluation of prostate tumors. The current research applies visual inspection and quantitative approaches, such as artificial intelligence (AI) based on deep learning (DL), to evaluate MRI. Recently, a different spectral/statistical approach has been used to successfully evaluate spatially registered biparametric MRIs for prostate cancer. This study aimed to further assess and improve the spectral/statistical approach through benchmarking and combination with AI. Methods: A zonal-aware self-supervised mesh network (Z-SSMNet) was applied to the same 42-patient cohort from previous spectral/statistical studies. Using the probability of clinical significance of prostate cancer (PCsPCa) and a detection map, the affiliated tumor volume, eccentricity was computed for each patient. Linear and logistic regression were applied to the International Society of Urological Pathology (ISUP) grade and PCsPCa, respectively. The R, p-value, and area under the curve (AUROC) from the Z-SSMNet output were computed. The Z-SSMNet output was combined with the spectral/statistical output for multiple-variate regression. Results: The R (p-value)–AUROC [95% confidence interval] from the Z-SSMNet algorithm relating ISUP to PCsPCa is 0.298 (0.06), 0.50 [0.08–1.0]; relating it to the average blob volume, it is 0.51 (0.0005), 0.37 [0.0–0.91]; relating it to total tumor volume, it is 0.36 (0.02), 0.50 [0.0–1.0]. The R (p-value)–AUROC computations showed a much poorer correlation for eccentricity derived from the Z-SSMNet detection map. Overall, DL/AI showed poorer performance relative to the spectral/statistical approaches from previous studies. Multi-variable regression fitted AI average blob size and SCR results at a level of R = 0.70 (0.000003), significantly higher than the results for the univariate regression fits for AI and spectral/statistical approaches alone. Conclusions: The spectral/statistical approaches performed well relative to Z-SSMNet. Combining Z-SSMNet with spectral/statistical approaches significantly enhanced tumor grade prediction, possibly providing an alternative to current prostate tumor assessment.

Background Prostate cancer management optimally requires non-invasive, objective, quantitative, accurate evalua-tion of prostate tumors. Current research applies visual inspection and quantitative approaches, such as artificial intelligence (AI) focused in deep learning (DL) to evaluate MRI. Recently, a different spectral/statistical approach successfully evaluated spatially registered bi-parametric MRIs for prostate cancer. This study aimed to further as-sess and improve the spectral/statistics approach through benchmarking and combining with AI. Methods A zonal-aware self-supervised mesh network (Z-SSMNet) was applied to the same 42-patient cohort from previous spectral/statistical studies. The probability of clinical significance of prostate cancer (PCsPCa) and detec-tion map with affiliated tumor volume, eccentricity were computed for each patient. Linear and logistic regression were applied to International Society of Urological Pathology (ISUP) grade and PCsPCa, respectively. The R, p-value, Area Under the Curve (AUROC) from Z-SSMNet output was computed The Z-SSMNet output was combined with spectral/statistics output for multiple-variate regression. Results The R (p-value), AUROC [95% Confidence Interval] from Z-SSMNet algorithm relating ISUP to PCsPCa is 0.298 (0.06), 0.50 [0.08-1.0], to average blob volume is 0.51 (0.0005), 0.37 [0.0-0.91], to total tumor volume is 0.36 (0.02), 0.50 [0.0-1.0]. R (p-value), AUROC computations showed much poorer correlation for eccentricity derived from Z-SSMNet detection map with ISUP. Overall DL/AI performed less well relative to spectral/statistical approaches from previous studies. Multi-variable regression fitted AI average blob size and SCR results in R=0.70 (0.000003) significantly higher than univariate regression fits of AI, spectral/statistics alone. Conclusions. Spectral/statistical approaches performed well relative to Z-SSMNet. Combining Z-SSMNet with spectral/statistics approaches significantly enhanced tumor grade prediction, possibly providing an alternative to current prostate tumor assessment.

This Special Topics Issue, “Imaging-based Diagnosis of Prostate Cancer—State of the Art”, of Diagnostics compiles 10 select articles

Background: Accurate, reliable, non-invasive assessment of patients diagnosed with prostate cancer is essential for proper disease management. Quantitative assessment of multi-parametric MRI, such as through artificial intelligence or spectral/statistical approaches, can provide a non-invasive objective determination of the prostate tumor aggressiveness without side effects or potential poor sampling from needle biopsy or overdiagnosis from prostate serum antigen measurements. To simplify and expedite prostate tumor evaluation, this study examined the efficacy of autonomously extracting tumor spectral signatures for spectral/statistical algorithms for spatially registered bi-parametric MRI. Methods: Spatially registered hypercubes were digitally constructed by resizing, translating, and cropping from the image sequences (Apparent Diffusion Coefficient (ADC), High B-value, T2) from 42 consecutive patients in the bi-parametric MRI PI-CAI dataset. Prostate cancer blobs exceeded a threshold applied to the registered set from normalizing the registered set into an image that maximizes High B-value, but minimizes the ADC and T2 images, appearing “green” in the color composite. Clinically significant blobs were selected based on size, average normalized green value, sliding window statistics within a blob, and position within the hypercube. The center of mass and maximized sliding window statistics within the blobs identified voxels associated with tumor signatures. We used correlation coefficients (R) and p-values, to evaluate the linear regression fits of the z-score and SCR (with processed covariance matrix) to tumor aggressiveness, as well as Area Under the Curves (AUC) for Receiver Operator Curves (ROC) from logistic probability fits to clinically significant prostate cancer. Results: The highest R (R > 0.45), AUC (>0.90), and lowest p-values (<0.01) were achieved using z-score and modified registration applied to the covariance matrix and tumor signatures selected from the “greenest” parts from the selected blob. Conclusions: The first autonomous tumor signature applied to spatially registered bi-parametric MRI shows promise for determining prostate tumor aggressiveness.

(1) Background: Non-invasive prostate cancer assessments using multi-parametric MRI are essential to the reliable detection of lesions and proper management of patients. While current guidelines call for the administration of Gadolinium-containing intravenous contrast injections, eliminating such injections would simplify scanning and reduce patient risk and costs. However, augmented image analysis is necessary to extract important diagnostic information from MRIs. Purpose: This study aims to extend previous work on the signal to clutter ratio and test whether prostate tumor eccentricity and volume are indicators of tumor aggressiveness using bi-parametric (BP)-MRI. (2) Methods: This study retrospectively processed 42 consecutive prostate cancer patients from the PI-CAI data collection. BP-MRIs (apparent diffusion coefficient, high b-value, and T2 images) were resized, translated, cropped, and stitched to form spatially registered BP-MRIs. The International Society of Urological Pathology (ISUP) grade was used to judge cases of prostate cancer as either clinically significant prostate cancer (CsPCa) (ISUP ≥ 2) or clinically insignificant prostate cancer (CiPCa) (ISUP < 2). The Adaptive Cosine Estimator (ACE) algorithm was applied to the BP-MRIs, followed by thresholding, and then eccentricity and volume computations, from the labeled and blobbed detection maps. Then, univariate and multivariate linear regression fittings of eccentricity and volume were applied to the ISUP grade. The fits were quantitatively evaluated by computing correlation coefficients (R) and p-values. Area under the curve (AUC) and receiver operator characteristic (ROC) curve scores were used to assess the logistic fitting to CsPCa/CiPCa. (3) Results: Modest correlation coefficients (R) (>0.35) and AUC scores (0.70) for the linear and/or logistic fits from the processed prostate tumor eccentricity and volume computations for the spatially registered BP-MRIs exceeded fits using the parameters of prostate serum antigen, prostate volume, and patient age (R~0.17). (4) Conclusions: This is the first study that applied spectral approaches to BP-MRIs to generate tumor eccentricity and volume metrics to assess tumor aggressiveness. This study found significant values of R and AUC (albeit below those from multi-parametric MRI) to fit and relate the metrics to the ISUP grade and CsPCA/CiPCA, respectively.

Background: Current prostate cancer evaluation can be inaccurate and burdensome. Quantitative evaluation of Magnetic Resonance Imaging (MRI) sequences non-invasively helps prostate tumor assessment. However, including Dynamic Contrast Enhancement (DCE) in the examined MRI sequence set can add complications, inducing possible side effects from the IV placement or injected contrast material and prolonging scanning time. More accurate quantitative MRI without DCE and artificial intelligence approaches are needed. Purpose: Predict the risk of developing Clinically Significant (Insignificant) prostate cancer CsPCa (CiPCa) and correlate with the International Society of Urologic Pathology (ISUP) grade using processed Signal to Clutter Ratio (SCR) derived from spatially registered bi-parametric MRI (SRBP-MRI) and thereby enhance non-invasive management of prostate cancer. Methods: This pilot study retrospectively analyzed 42 consecutive prostate cancer patients from the PI-CAI data collection. BP-MRI (Apparent Diffusion Coefficient, High B-value, T2) were resized, translated, cropped, and stitched to form spatially registered SRBP-MRI. Efficacy of noise reduction was tested by regularizing, eliminating principal components (PC), and minimizing elliptical volume from the covariance matrix to optimize the SCR. MRI guided biopsy (MRBx), Systematic Biopsy (SysBx), combination (MRBx + SysBx), or radical prostatectomy determined the ISUP grade for each patient. ISUP grade ≥ 2 (0.55) and high AUC (=1.0) for linear and/or logistic fit from processed SCR and z-score for SRBP-MRI greatly exceed fits using prostate serum antigen, prostate volume, and patient age (R ~ 0.17). Patients assessed with combined MRBx + SysBx and from individual MRI scanners achieved higher R (DR = 0.207+/−0.118) than all patients used in the fits. Conclusions: In the first study, to date, spectral approaches for assessing tumor aggressiveness on SRBP-MRI have been applied and tested and achieved high values of R and exceptional AUC to fit the ISUP grade and CsPCA/CiPCA, respectively.

Background: Current prostate cancer evaluation can be inaccurate and burdensome. Quantitative evaluation of MRI sequences non-invasively helps prostate tumor assessment. However, including Dynamic Contrast Enhancement in the examined MRI sequence set can add complications, inducing possible side effects from the IV placement or injected contrast material, and prolongs scanning time. Purpose: Predict the risk of developing Clinically Significant (Insignificant) prostate cancer CsPCa (CiPCa) and International Society of Urologic Pathology (ISUP) grade using processed Signal to Clutter Ratio (SCR) derived from spatially registered bi-parametric MRI (SRBP-MRI) and thereby enhance non-invasively management of prostate cancer. Methods: This pilot study retrospectively analyzed 42 consecutive prostate cancer patients from the PI-CAI data collection. BP-MRI (Apparent Diffusion Coefficient, High B-value, T2) were resized, translated, cropped, and stitched to form spatially registered SRBP-MRI. Efficacy of noise reduction was tested by regularizing, eliminating principal components (PC), and minimizing elliptical volume from the covariance matrix to optimize the SCR. MRI guided biopsy (MRBx), Systematic Biopsy (SysBx), combination (MRBx+SysBx), or radical prostatectomy determined the ISUP grade for each patient. ISUP grade >=2 (0.55) and high AUC (=1.0) for linear and/or logistic fit from processed SCR and z-score for SRBP-MRI greatly exceed fits using prostate serum antigen, prostate volume, and patient age (R~0.17). Patients assessed with combined MRBx+SysBx and from individual MRI scanners achieved higher R (R=0.207+/-0.118) than using all patients in the fits. Conclusions: In the first study to date to apply and test hyperspectral approaches for assessing tumor aggressiveness on SRBP-MRI, high values of R and exceptional AUC to fit the ISUP grade and CsPCA/CiPCA were comparable or better than those from artificial intelligence in other studies.

Editorial: Combining multiple non-invasive images and/or biochemical tests to predict prostate cancer aggressiveness

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.