Update on PI-RADS Version 2.1 Diagnostic Performance Benchmarks for Prostate MRI: Systematic Review and Meta-Analysis.

Background Prostate MRI for the detection of clinically significant prostate cancer (csPCa) is standardized by the Prostate Imaging Reporting and Data System (PI-RADS), currently in version 2.1. A systematic review and meta-analysis infrastructure with a 12-month update cycle was established to evaluate the diagnostic performance of PI-RADS over time. Purpose To provide estimates of diagnostic accuracy and cancer detection rates (CDRs) of PI-RADS version 2.1 categories for prostate MRI, which is required for further evidence-based patient management. Materials and Methods A systematic search of PubMed, Embase, Cochrane Library, and multiple trial registers (English-language studies published from March 1, 2019, to August 30, 2022) was performed. Studies that reported data on diagnostic accuracy or CDRs of PI-RADS version 2.1 with csPCa as the primary outcome were included. For the meta-analysis, pooled estimates for sensitivity, specificity, and CDRs were derived from extracted data at the lesion level and patient level. Sensitivity and specificity for PI-RADS greater than or equal to 3 and PI-RADS greater than or equal to 4 considered as test positive were investigated. In addition to individual PI-RADS categories 1-5, subgroup analyses of subcategories (ie, 2+1, 3+0) were performed. Results A total of 70 studies (11 686 lesions, 13 330 patients) were included. At the patient level, with PI-RADS greater than or equal to 3 considered positive, meta-analysis found a 96% summary sensitivity (95% CI: 95, 98) and 43% specificity (95% CI: 33, 54), with an area under the summary receiver operating characteristic (SROC) curve of 0.86 (95% CI: 0.75, 0.93). For PI-RADS greater than or equal to 4, meta-analysis found an 89% sensitivity (95% CI: 85, 92) and 66% specificity (95% CI: 58, 74), with an area under the SROC curve of 0.89 (95% CI: 0.85, 0.92). CDRs were as follows: PI-RADS 1, 6%; PI-RADS 2, 5%; PI-RADS 3, 19%; PI-RADS 4, 54%; and PI-RADS 5, 84%. The CDR was 12% (95% CI: 7, 19) for transition zone 2+1 lesions and 19% (95% CI: 12, 29) for 3+0 lesions (P = .12). Conclusion Estimates of diagnostic accuracy and CDRs for PI-RADS version 2.1 categories are provided for quality benchmarking and to guide further evidence-based patient management. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Tammisetti and Jacobs in this issue.

Deep learning reconstructed T2-weighted Dixon imaging of the spine: Impact on acquisition time and image quality.

PURPOSE: To assess the image quality and impact on acquisition time of a novel deep learning based T2 Dixon sequence (T2DL) of the spine. METHODS: This prospective, single center study included n = 44 consecutive patients with a clinical indication for lumbar MRI at our university radiology department between September 2022 and March 2023. MRI examinations were performed on 1.5-T and 3-T scanners (MAGNETOM Aera and Vida; Siemens Healthineers, Erlangen, Germany) using dedicated spine coils. The MR study protocol consisted of our standard clinical protocol, including a T2 weighted standard Dixon sequence (T2std) and an additional T2DL acquisition. The latter used a conventional sampling pattern with a higher parallel acceleration factor. The individual contrasts acquired for Dixon water-fat separation were then reconstructed using a dedicated research application. After reconstruction of the contrast images from k-space data, a conventional water-fat separation was performed to provide derived water images. Two readers with 6 and 4 years of experience in interpreting MSK imaging, respectively, analyzed the images in a randomized fashion. Regarding overall image quality, banding artifacts, artifacts, sharpness, noise, and diagnostic confidence were analyzed using a 5-point Likert scale (from 1 = non-diagnostic to 5 = excellent image quality). Statistical analyses included the Wilcoxon signed-rank test and weighted Cohen's kappa statistics. RESULTS: Forty-four patients (mean age 53 years (±18), male sex: 39 %) were prospectively included. Thirty-one examinations were performed on 1.5 T and 13 examinations on 3 T scanners. A sequence was successfully acquired in all patients. The total acquisition time of T2DL was 93 s at 1.5-T and 86 s at 3-T, compared to 235 s, and 257 s, respectively for T2std (reduction of acquisition time: 60.4 % at 1.5-T, and 66.5 % at 3-T; p < 0.01). Overall image quality was rated equal for both sequences (median T2DL: 5[3 -5], and median T2std: 5 [2 -5]; p = 0.57). T2DL showed significantly reduced noise levels compared to T2std (5 [4 -5] versus 4 [3 -4]; p < 0.001). In addition, sharpness was rated to be significantly higher in T2DL (5 [4 -5] versus 4 [3 -5]; p < 0.001). Although T2DL displayed significantly more banding artifacts (5 [2 -5] versus 5 [4 -5]; p < 0.001), no significant impact on readers diagnostic confidence between sequences was noted (T2std: 5 [2 -5], and T2DL: 5 [3 -5]; p = 0.61). Substantial inter-reader and intrareader agreement was observed for T2DL overall image quality (κ: 0.77, and κ: 0.8, respectively). CONCLUSION: T2DL is feasible, yields an image quality comparable to the reference standard while substantially reducing the acquisition time.

Comparison of data fusion strategies for automated prostate lesion detection using mpMRI correlated with whole mount histology.

BACKGROUND: In this work, we compare input level, feature level and decision level data fusion techniques for automatic detection of clinically significant prostate lesions (csPCa). METHODS: Multiple deep learning CNN architectures were developed using the Unet as the baseline. The CNNs use both multiparametric MRI images (T2W, ADC, and High b-value) and quantitative clinical data (prostate specific antigen (PSA), PSA density (PSAD), prostate gland volume & gross tumor volume (GTV)), and only mp-MRI images (n = 118), as input. In addition, co-registered ground truth data from whole mount histopathology images (n = 22) were used as a test set for evaluation. RESULTS: The CNNs achieved for early/intermediate / late level fusion a precision of 0.41/0.51/0.61, recall value of 0.18/0.22/0.25, an average precision of 0.13 / 0.19 / 0.27, and F scores of 0.55/0.67/ 0.76. Dice Sorensen Coefficient (DSC) was used to evaluate the influence of combining mpMRI with parametric clinical data for the detection of csPCa. We compared the DSC between the predictions of CNN's trained with mpMRI and parametric clinical and the CNN's trained with only mpMRI images as input with the ground truth. We obtained a DSC of data 0.30/0.34/0.36 and 0.26/0.33/0.34 respectively. Additionally, we evaluated the influence of each mpMRI input channel for the task of csPCa detection and obtained a DSC of 0.14 / 0.25 / 0.28. CONCLUSION: The results show that the decision level fusion network performs better for the task of prostate lesion detection. Combining mpMRI data with quantitative clinical data does not show significant differences between these networks (p = 0.26/0.62/0.85). The results show that CNNs trained with all mpMRI data outperform CNNs with less input channels which is consistent with current clinical protocols where the same input is used for PI-RADS lesion scoring. TRIAL REGISTRATION: The trial was registered retrospectively at the German Register for Clinical Studies (DRKS) under proposal number Nr. 476/14 & 476/19.

Ex Vivo Fluorescence Confocal Microscopy of MRI-Guided Targeted Prostate Biopsies for Rapid Detection of Clinically Significant Carcinomas-A Feasibility Study.

BACKGROUND: MRI-guided prostate biopsies from visible tumor-specific lesions (TBx) can be used to diagnose clinically significant carcinomas (csPCa) requiring treatment more selectively than conventional systematic biopsies (SBx). Ex vivo fluorescence confocal microscopy (FCM) is a novel technique that can be used to examine TBx prior to conventional histologic workup. METHODS: TBx from 150 patients were examined with FCM on the day of collection. Preliminary findings were reported within 2 h of collection. The results were statistically compared with the final histology. RESULTS: 27/40 (68%) of the csPCa were already recognized in the intraday FCM in accordance with the results of conventional histology. Even non-significant carcinomas (cisPCa) of the intermediate and high-risk groups (serum prostate-specific antigen (PSA) > 10 or 20 ng/mL) according to conventional risk stratifications were reliably detectable. In contrast, small foci of cisPCa were often not detected or were difficult to distinguish from reactive changes. CONCLUSION: The rapid reporting of preliminary FCM findings helps to reduce the psychological stress on patients, and can improve the clinical management of csPCa. Additional SBx can be avoided in individual cases, leading to lower rates of complications and scarring in the future surgical area. Additional staging examinations can be arranged without losing time. FCM represents a promising basis for future AI-based diagnostic algorithms.

Ultrashort VIBE-Dixon versus Cine and late gadolinium enhancement MRI sequences for cardiac thrombus detection.

PURPOSE: To determine the diagnostic accuracy of volumetric interpolated breath-hold examination sequences with fat suppression in Dixon technique (VIBE-Dixon) for cardiac thrombus detection. METHOD: From our clinical database, we retrospectively identified consecutive patients between 2014 and 2022 who had definite diagnosis or exclusion of cardiac thrombus confirmed by an independent adjudication committee, serving as the reference standard. All patients received 2D-Cine plus 2D-Late-Gadolinium-Enhancement (Cine + LGE) and VIBE-Dixon sequences. Two blinded readers assessed all images for the presence of cardiac thrombus. The diagnostic accuracy of Cine + LGE and VIBE-Dixon was determined and compared. RESULTS: Among 141 MRI studies (116 male, mean age: 61 years) mean image examination time was 28.8 ± 3.1 s for VIBE-Dixon and 23.3 ± 2.5 min for Cine + LGE. Cardiac thrombus was present in 49 patients (prevalence: 35 %). For both readers sensitivity for thrombus detection was significantly higher in VIBE-Dixon compared with Cine + LGE (Reader 1: 96 % vs.73 %, Reader 2: 96 % vs. 78 %, p < 0.01 for both readers), whereas specificity did not differ significantly (Reader 1: 96 % vs. 98 %, Reader 2: 92 % vs. 93 %, p > 0.1). Overall diagnostic accuracy of VIBE-Dixon was higher than for Cine + LGE (95 % vs. 89 %, p = 0.02) and was non-inferior to the reference standard (Delta ≤ 5 % with probability > 95 %). CONCLUSIONS: Biplanar VIBE-Dixon sequences, acquired within a few seconds, provided a very high diagnostic accuracy for cardiac thrombus detection. They could be used as stand-alone sequences to rapidly screen for cardiac thrombus in patients not amenable to lengthy acquisition times.

A Machine Learning Framework Reduces the Manual Workload for Systematic Reviews of the Diagnostic Performance of Prostate Magnetic Resonance Imaging.

Prostate magnetic resonance imaging has become the imaging standard for prostate cancer in various clinical settings, with interpretation standardized according to the Prostate Imaging Reporting and Data System (PI-RADS). Each year, hundreds of scientific studies that report on the diagnostic performance of PI-RADS are published. To keep up with this ever-increasing evidence base, systematic reviews and meta-analyses are essential. As systematic reviews are highly resource-intensive, we investigated whether a machine learning framework can reduce the manual workload and speed up the screening process (title and abstract). We used search results from a living systematic review of the diagnostic performance of PI-RADS (1585 studies, of which 482 were potentially eligible after screening). A naïve Bayesian classifier was implemented in an active learning environment for classification of the titles and abstracts. Our outcome variable was the percentage of studies that can be excluded after 95% of relevant studies have been identified by the classifier (work saved over sampling: WSS@95%). In simulation runs of the entire screening process (controlling for classifier initiation and the frequency of classifier updating), we obtained a WSS@95% value of 28% (standard error of the mean ±0.1%). Applied prospectively, our classification framework would translate into a significant reduction in manual screening effort. Patient summary: Systematic reviews of scientific evidence are labor-intensive and take a lot of time. For example, many studies on prostate cancer diagnosis via MRI (magnetic resonance imaging) are published every year. We describe the use of machine learning to reduce the manual workload in screening search results. For a review of MRI for prostate cancer diagnosis, this approach reduced the screening workload by about 28%.

Accelerated Diffusion-Weighted Imaging in 3 T Breast MRI Using a Deep Learning Reconstruction Algorithm With Superresolution Processing: A Prospective Comparative Study.

OBJECTIVES: Diffusion-weighted imaging (DWI) enhances specificity in multiparametric breast MRI but is associated with longer acquisition time. Deep learning (DL) reconstruction may significantly shorten acquisition time and improve spatial resolution. In this prospective study, we evaluated acquisition time and image quality of a DL-accelerated DWI sequence with superresolution processing (DWI DL ) in comparison to standard imaging including analysis of lesion conspicuity and contrast of invasive breast cancers (IBCs), benign lesions (BEs), and cysts. MATERIALS AND METHODS: This institutional review board-approved prospective monocentric study enrolled participants who underwent 3 T breast MRI between August and December 2022. Standard DWI (DWI STD ; single-shot echo-planar DWI combined with reduced field-of-view excitation; b-values: 50 and 800 s/mm 2 ) was followed by DWI DL with similar acquisition parameters and reduced averages. Quantitative image quality was analyzed for region of interest-based signal-to-noise ratio (SNR) on breast tissue. Apparent diffusion coefficient (ADC), SNR, contrast-to-noise ratio, and contrast (C) values were calculated for biopsy-proven IBCs, BEs, and for cysts. Two radiologists independently assessed image quality, artifacts, and lesion conspicuity in a blinded independent manner. Univariate analysis was performed to test differences and interrater reliability. RESULTS: Among 65 participants (54 ± 13 years, 64 women) enrolled in the study, the prevalence of breast cancer was 23%. Average acquisition time was 5:02 minutes for DWI STD and 2:44 minutes for DWI DL ( P < 0.001). Signal-to-noise ratio measured in breast tissue was higher for DWI STD ( P < 0.001). The mean ADC values for IBC were 0.77 × 10 -3 ± 0.13 mm 2 /s in DWI STD and 0.75 × 10 -3 ± 0.12 mm 2 /s in DWI DL without significant difference when sequences were compared ( P = 0.32). Benign lesions presented with mean ADC values of 1.32 × 10 -3 ± 0.48 mm 2 /s in DWI STD and 1.39 × 10 -3 ± 0.54 mm 2 /s in DWI DL ( P = 0.12), and cysts presented with 2.18 × 10 -3 ± 0.49 mm 2 /s in DWI STD and 2.31 × 10 -3 ± 0.43 mm 2 /s in DWI DL . All lesions presented with significantly higher contrast in the DWI DL ( P < 0.001), whereas SNR and contrast-to-noise ratio did not differ significantly between DWI STD and DWI DL regardless of lesion type. Both sequences demonstrated a high subjective image quality (29/65 for DWI STD vs 20/65 for DWI DL ; P < 0.001). The highest lesion conspicuity score was observed more often for DWI DL ( P < 0.001) for all lesion types. Artifacts were scored higher for DWI DL ( P < 0.001). In general, no additional artifacts were noted in DWI DL . Interrater reliability was substantial to excellent (k = 0.68 to 1.0). CONCLUSIONS: DWI DL in breast MRI significantly reduced scan time by nearly one half while improving lesion conspicuity and maintaining overall image quality in a prospective clinical cohort.

Enhancing Radiation Dose Efficiency in Prospective ECG-Triggered Coronary CT Angiography Using Calcium-Scoring CT.

BACKGROUND: This study investigates whether the scan length adjustment of prospectively ECG-triggered coronary CT angiography (CCTA) using calcium-scoring CT (CAS-CT) images can reduce overall radiation doses. METHODS: A retrospective analysis was conducted on 182 patients who underwent CAS-CT and prospectively ECG-triggered CCTA using a second-generation Dual-Source CT scanner. CCTA planning was based on CAS-CT images, for which simulated scout view planning was performed for comparison. Effective doses were compared between two scenarios: Scenario 1-CAS-CT-derived CCTA + CAS-CT and Scenario 2-scout-view-derived CCTA without CAS-CT. Dose differences were further analyzed with respect to scan mode and body mass index. RESULTS: Planning CCTA using CAS-CT led to a shorter scan length than planning via scout view (114.3 ± 9.7 mm vs. 133.7 ± 13.2 mm, p < 0.001). The whole-examination effective dose was slightly lower for Scenario 1 (3.2 [1.8-5.3] mSv vs. 3.4 [1.5-5.9] mSv; p < 0.001, n = 182). Notably, Scenario 1 resulted in a significantly lower radiation dose for sequential scans and obese patients. Only high-pitch spiral CCTA showed dose reduction in Scenario 2. CONCLUSIONS: Using CAS-CT for planning prospectively ECG-triggered CCTA reduced the overall radiation dose administered compared to scout view planning without CAS-CT, except for high-pitch spiral CCTA, where a slightly opposite effect was observed.

Investigation and benchmarking of U-Nets on prostate segmentation tasks.

In healthcare, a growing number of physicians and support staff are striving to facilitate personalized radiotherapy regimens for patients with prostate cancer. This is because individual patient biology is unique, and employing a single approach for all is inefficient. A crucial step for customizing radiotherapy planning and gaining fundamental information about the disease, is the identification and delineation of targeted structures. However, accurate biomedical image segmentation is time-consuming, requires considerable experience and is prone to observer variability. In the past decade, the use of deep learning models has significantly increased in the field of medical image segmentation. At present, a vast number of anatomical structures can be demarcated on a clinician's level with deep learning models. These models would not only unload work, but they can offer unbiased characterization of the disease. The main architectures used in segmentation are the U-Net and its variants, that exhibit outstanding performances. However, reproducing results or directly comparing methods is often limited by closed source of data and the large heterogeneity among medical images. With this in mind, our intention is to provide a reliable source for assessing deep learning models. As an example, we chose the challenging task of delineating the prostate gland in multi-modal images. First, this paper provides a comprehensive review of current state-of-the-art convolutional neural networks for 3D prostate segmentation. Second, utilizing public and in-house CT and MR datasets of varying properties, we created a framework for an objective comparison of automatic prostate segmentation algorithms. The framework was used for rigorous evaluations of the models, highlighting their strengths and weaknesses.

Multiparametric magnetic resonance imaging for radiation therapy response monitoring in soft tissue sarcomas: a histology and MRI co-registration algorithm.

Rationale: To establish a spatially exact co-registration procedure between in vivo multiparametric magnetic resonance imaging (mpMRI) and (immuno)histopathology of soft tissue sarcomas (STS) to identify imaging parameters that reflect radiation therapy response of STS. Methods: The mpMRI-Protocol included diffusion-weighted (DWI), intravoxel-incoherent motion (IVIM), and dynamic contrast-enhancing (DCE) imaging. The resection specimen was embedded in 6.5% agarose after initial fixation in formalin. To ensure identical alignment of histopathological sectioning and in vivo imaging, an ex vivo MRI scan of the specimen was rigidly co-registered with the in vivo mpMRI. The deviating angulation of the specimen to the in vivo location of the tumor was determined. The agarose block was trimmed accordingly. A second ex vivo MRI in a dedicated localizer with a 4 mm grid was performed, which was matched to a custom-built sectioning machine. Microtomy sections were stained with hematoxylin and eosin. Immunohistochemical staining was performed with anti-ALDH1A1 antibodies as a radioresistance and anti-MIB1 antibodies as a proliferation marker. Fusion of the digitized microtomy sections with the in vivo mpMRI was accomplished through nonrigid co-registration to the in vivo mpMRI. Co-registration accuracy was qualitatively assessed by visual assessment and quantitatively evaluated by computing target registration errors (TRE). Results: The study sample comprised nine tumor sections from three STS patients. Visual assessment after nonrigid co-registration showed a strong morphological correlation of the histopathological specimens with ex vivo MRI and in vivo mpMRI after neoadjuvant radiation therapy. Quantitative assessment of the co-registration procedure using TRE analysis of different pairs of pathology and MRI sections revealed highly accurate structural alignment, with a total median TRE of 2.25 mm (histology - ex vivo MRI), 2.22 mm (histology - in vivo mpMRI), and 2.02 mm (ex vivo MRI - in vivo mpMRI). There was no significant difference between TREs of the different pairs of sections or caudal, middle, and cranial tumor parts, respectively. Conclusion: Our initial results show a promising approach to obtaining accurate co-registration between histopathology and in vivo MRI for STS. In a larger cohort of patients, the method established here will enable the prospective identification and validation of in vivo imaging biomarkers for radiation therapy response prediction and monitoring in STS patients via precise molecular and cellular correlation.

Development of PSMA-PET-guided CT-based radiomic signature to predict biochemical recurrence after salvage radiotherapy.

PURPOSE: To develop a CT-based radiomic signature to predict biochemical recurrence (BCR) in prostate cancer patients after sRT guided by positron-emission tomography targeting prostate-specific membrane antigen (PSMA-PET). MATERIAL AND METHODS: Consecutive patients, who underwent 68Ga-PSMA11-PET/CT-guided sRT from three high-volume centers in Germany, were included in this retrospective multicenter study. Patients had PET-positive local recurrences and were treated with intensity-modulated sRT. Radiomic features were extracted from volumes of interests on CT guided by focal PSMA-PET uptakes. After preprocessing, clinical, radiomics, and combined clinical-radiomic models were developed combining different feature reduction techniques and Cox proportional hazard models within a nested cross validation approach. RESULTS: Among 99 patients, median interval until BCR was the radiomic models outperformed clinical models and combined clinical-radiomic models for prediction of BCR with a C-index of 0.71 compared to 0.53 and 0.63 in the test sets, respectively. In contrast to the other models, the radiomic model achieved significantly improved patient stratification in Kaplan-Meier analysis. The radiomic and clinical-radiomic model achieved a significantly better time-dependent net reclassification improvement index (0.392 and 0.762, respectively) compared to the clinical model. Decision curve analysis demonstrated a clinical net benefit for both models. Mean intensity was the most predictive radiomic feature. CONCLUSION: This is the first study to develop a PSMA-PET-guided CT-based radiomic model to predict BCR after sRT. The radiomic models outperformed clinical models and might contribute to guide personalized treatment decisions.

Prediction of upgrade to clinically significant prostate cancer in patients under active surveillance: Performance of a fully automated AI-algorithm for lesion detection and classification.

BACKGROUND: Multiparametric MRI (mpMRI) improves the detection of aggressive prostate cancer (PCa) subtypes. As cases of active surveillance (AS) increase and tumor progression triggers definitive treatment, we evaluated whether an AI-driven algorithm can detect clinically significant PCa (csPCa) in patients under AS. METHODS: Consecutive patients under AS who received mpMRI (PI-RADSv2.1 protocol) and subsequent MR-guided ultrasound fusion (targeted and extensive systematic) biopsy between 2017 and 2020 were retrospectively analyzed. Diagnostic performance of an automated clinically certified AI-driven algorithm was evaluated on both lesion and patient level regarding the detection of csPCa. RESULTS: Analysis of 56 patients resulted in 93 target lesions. Patient level sensitivity and specificity of the AI algorithm was 92.5%/31% for the detection of ISUP ≥ 1 and 96.4%/25% for the detection of ISUP ≥ 2, respectively. The only case of csPCa missed by the AI harbored only 1/47 Gleason 7a core (systematic biopsy; previous and subsequent biopsies rendered non-csPCa). CONCLUSIONS: AI-augmented lesion detection and PI-RADS scoring is a robust tool to detect progression to csPCa in patients under AS. Integration in the clinical workflow can serve as reassurance for the reader and streamline reporting, hence improve efficiency and diagnostic confidence.

Individualized Decision Making in Transperineal Prostate Biopsy: Should All Men Undergo an Additional Systematic Biopsy?

Background: In prostate cancer (PC) diagnosis, additional systematic biopsy (SB) is recommended to complement MRI-targeted biopsy (TB) to address the limited sensitivity of TB alone. The combination of TB+SB is beneficial for diagnosing additional significant PC (sPC) but harmful in terms of the additional diagnosis of indolent PC (iPC), morbidity, and resource expenditures. We aimed to investigate the benefit of additional SB and to identify predictors for this outcome. Methods: We analyzed the frequency of upgrading to sPC by additional SB in a retrospective single-center cohort of 1043 men. Regression analysis (RA) was performed to identify predictors for this outcome. Reclassification rates of ISUP grade groups between prostate biopsy and a subsequent radical prostatectomy were assessed. Results: Additional SB led to upgrading to sPC in 98/1043 men (9.4%) and to the additional diagnosis of iPC in 71/1043 (6.8%). In RA, men harboring a PI-RADS 2-4 lesion were more likely to have TB results upgraded by SB (p < 0.01) compared to PI-RADS 5 men. When analyzing reclassification rates, additional SB reduced the upgrading to sPC from 43/214 (20.1%) to 8/214 (3.7%). In the PI-RADS 5 subgroup, this difference decreased: 4/87 (4.7%) with TB only vs. 1/87 (1.2%) with TB+SB. Conclusion: Men with a PI-RADS 5 lesion may obviate additional SB.

Living systematic review and meta-analysis of the prostate MRI diagnostic test with Prostate Imaging Reporting and Data System (PI-RADS) assessment for the detection of prostate cancer: study protocol.

INTRODUCTION: The Prostate Imaging Reporting and Data System (PI-RADS) standardises reporting of prostate MRI for the detection of clinically significant prostate cancer. We provide the protocol of a planned living systematic review and meta-analysis for (1) diagnostic accuracy (sensitivity and specificity), (2) cancer detection rates of assessment categories and (3) inter-reader agreement. METHODS AND ANALYSIS: Retrospective and prospective studies reporting on at least one of the outcomes of interest are included. Each step that requires literature evaluation and data extraction is performed by two independent reviewers. Since PI-RADS is intended as a living document itself, a 12-month update cycle of the systematic review and meta-analysis is planned.This protocol is in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Protocols statement. The search strategies including databases, study eligibility criteria, index and reference test definitions, outcome definitions and data analysis processes are detailed. A full list of extracted data items is provided.Summary estimates of sensitivity and specificity (for PI-RADS ≥3 and PI-RADS ≥4 considered positive) are derived with bivariate binomial models. Summary estimates of cancer detection rates are calculated with random intercept logistic regression models for single proportions. Summary estimates of inter-reader agreement are derived with random effects models. ETHICS AND DISSEMINATION: No original patient data are collected, ethical review board approval, therefore, is not necessary. Results are published in peer-reviewed, open-access scientific journals. We make the collected data accessible as supplemental material to guarantee transparency of results. PROSPERO REGISTRATION NUMBER: CRD42022343931.

Ex vivo γH2AX assay for tumor radiosensitivity in primary prostate cancer patients and correlation with clinical parameters.

BACKROUND: Accurate surrogate parameters for radio resistance are warranted for individualized radiotherapy (RT) concepts in prostate cancer (PCa). The purpose of this study was to assess intertumoral heterogeneity in terms of radio resistance using an ex-vivo γH2AX assay after irradiation of prostate biopsy cores and to investigate its correlation with clinical features of respective patients as well as imaging and genomic features of tumor areas. METHODS: Twenty one patients with histologically-proven PCa and pre-therapeutic multiparametric resonance imaging and prostate-specific membrane antigen positron emission tomography were included in the study. Biopsy cores were collected from 26 PCa foci. Residual γH2AX foci were counted 24 h after ex-vivo irradiation (with 0 and 4 Gy) of biopsy specimen and served as a surrogate for radio resistance. Clinical, genomic (next generation sequencing) and imaging features were collected and their association with the radio resistance was studied. RESULTS: In total 18 PCa lesions from 16 patients were included in the final analysis. The median γH2AX foci value per PCa lesion was 3.12. According to this, the patients were divided into two groups (radio sensitive vs. radio resistant) with significant differences in foci number (p < 0.0001). The patients in the radio sensitive group had significantly higher prostate specific antigen serum concentration (p = 0.015), tumor areas in the radio sensitive group had higher SUV (standardized uptake values in PSMA PET)-max and -mean values (p = 0.0037, p = 0.028) and lower ADC (apparent diffusion coefficient-mean values, p = 0.049). All later parameters had significant (p < 0.05) correlations in Pearson's test. One patient in the radio sensitive group displayed a previously not reported loss of function frameshift mutation in the NBN gene (c.654_658delAAAAC) that introduces a premature termination codon and results in a truncated protein. CONCLUSION: In this pilot study, significant differences in intertumoral radio resistance were observed and clinical as well as imaging parameters may be applied for their prediction. After further prospective validation in larger patient cohorts these finding may lead to individual RT dose prescription for PCa patients in the future.

Quantitative Analysis of Diffusion Weighted Imaging May Improve Risk Stratification of Prostatic Transition Zone Lesions.

BACKGROUND/AIM: To investigate whether quantitative analysis of diffusion weighted images allows for improved risk stratification of transition zone lesions in prostate magnetic resonance imaging (MRI) evaluated according to PI-RADSv2.1 [Prostate Imaging Reporting and Data System, target variable: clinically significant prostate cancer (csPCa)]. PATIENTS AND METHODS: Consecutive patients with transition zone lesions in 3T prostate MRI were enrolled in the study. All lesions on MRI were histopathologically verified by transperineal MRI-TRUS fusion biopsy. Two blinded radiologists re-evaluated all lesions according to PI-RADSv2.1. A consensus reading was performed after reading of all cases. Additionally, mean apparent diffusion coefficient values (mADC) were derived from blinded lesion segmentation. ROC analysis was performed for PI-RADS categories and PI-RADS categories with separate subcategories and diffusion coefficient values (ADC). Data were examined for optimal mADC cut-off values that improve stratification of csPCa and benign lesions. RESULTS: Among 85 patients (mean age=66.2 years), 98 transition zone lesions were detected. Biopsy confirmed csPCa in 24/98 cases. Area under the curve (AUC) was 0.89/0.90 for reader 1, 0.92/0.91 for reader 2 and 0.92/0.91 for the consensus reading (5 category analysis/analysis with subcategories separately). Inter-reader agreement was substantial, with lower PI-RADS categories assigned by the more experienced reader (p<0.05). AUC for mADC alone was 0.81. When a cut-off threshold of 950 µm2/s mADC is used to downgrade PI-RADS 3 lesions to PI-RADS 2, biopsy could be avoided in all benign PI-RADS 3 cases. CONCLUSION: Quantitative analysis of diffusion weighted images may help avoid unnecessary biopsies of transition zone PI-RADS 3 lesions.

Intraindividual Comparison Between [18F] PSMA-1007 PET/CT and Multiparametric MRI for Radiotherapy Planning in Primary Prostate Cancer Patients.

Introduction: Accurate detection and segmentation of the intraprostatic gross tumor volume (GTV) is pivotal for radiotherapy (RT) in primary prostate cancer (PCa) since it influences focal therapy target volumes and the patients' cT stage. The study aimed to compare the performance of multiparametric resonance imaging (mpMRI) with [18F] PSMA-1007 positron emission tomography (PET) for intraprostatic GTV detection as well as delineation and to evaluate their respective influence on RT concepts. Materials and Methods: In total, 93 patients from two German University Hospitals with [18F] PSMA-1007-PET/CT and MRI (Freiburg) or [18F] PSMA-1007-PET/MRI (Dresden) were retrospectively enrolled. Validated contouring techniques were applied for GTV-PET and -MRI segmentation. Absolute tumor volume and cT status were determined for each imaging method. The PCa distribution from histopathological reports based on biopsy cores and surgery specimen was used as reference in terms of laterality (unilateral vs. bilateral). Results: In the Freiburg cohort (n = 84), mpMRI and PET detected in median 2 (range: 1-5) and 3 (range: 1-8) GTVs, respectively (p < 0.01). The median GTV-MRI was significantly smaller than the GTV-PET, measuring 2.05 vs. 3.65 ml (p = 0.0005). PET had a statistically significant higher concordance in laterality with surgery specimen compared to mpMRI (p = 0.04) and biopsy (p < 0.01), respectively. PSMA PET led to more cT2c and cT3b stages, whereas cT3a stage was more pronounced in mpMRI. Based on the cT stage derived from mpMRI and PET information, 21 and 23 as well as 59 and 60 patients, respectively, were intermediate- and high-risk according to the National Comprehensive Cancer Network (NCCN) v1.2022 criteria. In the Dresden cohort (n = 9), similar results were observed. Conclusion: Intraprostatic GTV segmentation based on [18F] PSMA-1007 PET results in more and larger GTVs compared to mpMRI. This influences focal RT target volumes and cT stage definition, but not the NCCN risk group.

[Image-guided biopsy of the prostate gland]. / Bildgesteuerte Biopsie der Prostata.

The recommendations on carrying out a multiparametric magnetic resonance imaging (mpMRI) for the primary diagnostics and during active surveillance of prostate cancer, include as a consequence an image-guided sampling from conspicuous areas. In doing so, the information on the localization provided by mpMRI is used for a targeted biopsy of the area suspected of being a tumor. The targeted sampling is mainly performed under sonographic control and after fusion of MRI and ultrasound but can also be (mostly in special cases) carried out directly in the MRI scanner. In an ultrasound-guided biopsy, it is vital to coregister the MR images with the ultrasound images (segmentation of the contour of the prostate and registration of suspect findings). This coregistration can either be carried out cognitively (transfer by the person performing the biopsy alone) or software based. Each method shows specific advantages and disadvantages in the prioritization between diagnostic accuracy and resource expenditure.

Explainable AI for CNN-based prostate tumor segmentation in multi-parametric MRI correlated to whole mount histopathology.

Automatic prostate tumor segmentation is often unable to identify the lesion even if multi-parametric MRI data is used as input, and the segmentation output is difficult to verify due to the lack of clinically established ground truth images. In this work we use an explainable deep learning model to interpret the predictions of a convolutional neural network (CNN) for prostate tumor segmentation. The CNN uses a U-Net architecture which was trained on multi-parametric MRI data from 122 patients to automatically segment the prostate gland and prostate tumor lesions. In addition, co-registered ground truth data from whole mount histopathology images were available in 15 patients that were used as a test set during CNN testing. To be able to interpret the segmentation results of the CNN, heat maps were generated using the Gradient Weighted Class Activation Map (Grad-CAM) method. The CNN achieved a mean Dice Sorensen Coefficient 0.62 and 0.31 for the prostate gland and the tumor lesions -with the radiologist drawn ground truth and 0.32 with whole-mount histology ground truth for tumor lesions. Dice Sorensen Coefficient between CNN predictions and manual segmentations from MRI and histology data were not significantly different. In the prostate the Grad-CAM heat maps could differentiate between tumor and healthy prostate tissue, which indicates that the image information in the tumor was essential for the CNN segmentation.