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.

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%.

Cancer detection rates of the PI-RADSv2.1 assessment categories: systematic review and meta-analysis on lesion level and patient level.

BACKGROUND: The Prostate Imaging Reporting and Data System, version 2.1 (PI-RADSv2.1) standardizes reporting of multiparametric MRI of the prostate. Assigned assessment categories are a risk stratification algorithm, higher categories indicate a higher probability of clinically significant cancer compared to lower categories. PI-RADSv2.1 does not define these probabilities numerically. We conduct a systematic review and meta-analysis to determine the cancer detection rates (CDR) of the PI-RADSv2.1 assessment categories on lesion level and patient level. METHODS: Two independent reviewers screen a systematic PubMed and Cochrane CENTRAL search for relevant articles (primary outcome: clinically significant cancer, index test: prostate MRI reading according to PI-RADSv2.1, reference standard: histopathology). We perform meta-analyses of proportions with random-effects models for the CDR of the PI-RADSv2.1 assessment categories for clinically significant cancer. We perform subgroup analysis according to lesion localization to test for differences of CDR between peripheral zone lesions and transition zone lesions. RESULTS: A total of 17 articles meet the inclusion criteria and data is independently extracted by two reviewers. Lesion level analysis includes 1946 lesions, patient level analysis includes 1268 patients. On lesion level analysis, CDR are 2% (95% confidence interval: 0-8%) for PI-RADS 1, 4% (1-9%) for PI-RADS 2, 20% (13-27%) for PI-RADS 3, 52% (43-61%) for PI-RADS 4, 89% (76-97%) for PI-RADS 5. On patient level analysis, CDR are 6% (0-20%) for PI-RADS 1, 9% (5-13%) for PI-RADS 2, 16% (7-27%) for PI-RADS 3, 59% (39-78%) for PI-RADS 4, 85% (73-94%) for PI-RADS 5. Higher categories are significantly associated with higher CDR (P < 0.001, univariate meta-regression), no systematic difference of CDR between peripheral zone lesions and transition zone lesions is identified in subgroup analysis. CONCLUSIONS: Our estimates of CDR demonstrate that PI-RADSv2.1 stratifies lesions and patients as intended. Our results might serve as an initial evidence base to discuss management strategies linked to assessment categories.

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.

Phantom study for comparison between computed tomography- and C-Arm computed tomography-guided puncture applied by residents in radiology. / Phantomstudie zum Vergleich zwischen Computertomografie- und C-Arm-Computertomografie-gesteuertem Punktionsverfahren bei Anwendung durch Weiterbildungsassistenten in der Radiologie.

PURPOSE: Comparison of puncture deviation and puncture duration between computed tomography (CT)- and C-arm CT (CACT)-guided puncture performed by residents in training (RiT). METHODS: In a cohort of 25 RiTs enrolled in a research training program either CT- or CACT-guided puncture was performed on a phantom. Prior to the experiments, the RiT's level of training, experience playing a musical instrument, video games, and ball sports, and self-assessed manual skills and spatial skills were recorded. Each RiT performed two punctures. The first puncture was performed with a transaxial or single angulated needle path and the second with a single or double angulated needle path. Puncture deviation and puncture duration were compared between the procedures and were correlated with the self-assessments. RESULTS: RiTs in both the CT guidance and CACT guidance groups did not differ with respect to radiologic experience (p = 1), angiographic experience (p = 0.415), and number of ultrasound-guided puncture procedures (p = 0.483), CT-guided puncture procedures (p = 0.934), and CACT-guided puncture procedures (p = 0.466). The puncture duration was significantly longer with CT guidance (without navigation tool) than with CACT guidance with navigation software (p < 0.001). There was no significant difference in the puncture duration between the first and second puncture using CT guidance (p = 0.719). However, in the case of CACT, the second puncture was significantly faster (p = 0.006). Puncture deviations were not different between CT-guided and CACT-guided puncture (p = 0.337) and between the first and second puncture of CT-guided and CACT-guided puncture (CT: p = 0.130; CACT: p = 0.391). The self-assessment of manual skills did not correlate with puncture deviation (p = 0.059) and puncture duration (p = 0.158). The self-assessed spatial skills correlated positively with puncture deviation (p = 0.011) but not with puncture duration (p = 0.541). CONCLUSION: The RiTs achieved a puncture deviation that was clinically adequate with respect to their level of training and did not differ between CT-guided and CACT-guided puncture. The puncture duration was shorter when using CACT. CACT guidance with navigation software support has a potentially steeper learning curve. Spatial skills might accelerate the learning of image-guided puncture. KEY POINTS: · The CT-guided and CACT-guided puncture experience of the RiTs selected as part of the program "Researchers for the Future" of the German Roentgen Society was adequate with respect to the level of training.. · Despite the lower collective experience of the RiTs with CACT-guided puncture with navigation software assistance, the learning curve regarding CACT-guided puncture may be faster compared to the CT-guided puncture technique.. · If the needle path is complex, CACT guidance with navigation software assistance might have an advantage over CT guidance.. CITATION FORMAT: · Meine TC, Hinrichs JB, Werncke T et al. Phantom study for comparison between computed tomography- and C-Arm computed tomography-guided puncture applied by residents in radiology. Fortschr Röntgenstr 2022; 194: 272 - 280.

Validation of color Doppler ultrasound and computed tomography in the radiologic assessment of non-malignant acute splanchnic vein thrombosis.

INTRODUCTION: International guidelines propose color Doppler ultrasound (CDUS) and contrast-enhanced computed tomography (CT) as primary imaging techniques in the diagnosis of acute splanchnic vein thrombosis. However, their reliability in this context is poorly investigated. Therefore, the aim of our study was to validate CDUS and CT in the radiologic assessment of acute splanchnic vein thrombosis, using direct transjugular spleno-portography as gold standard. MATERIALS AND METHODS: 49 patients with non-malignant acute splanchnic vein thrombosis were included in a retrospective, multicenter analysis. The thrombosis' extent in five regions of the splanchnic venous system (right and left intrahepatic portal vein, main trunk of the portal vein, splenic vein, superior mesenteric vein) and the degree of thrombosis (patent, partial thrombosis, complete thrombosis) were assessed by portography, CDUS and CT in a blinded manner. Reliability of CDUS and CT with regard to portography as gold standard was analyzed by calculating Cohen's kappa. RESULTS: Results of CDUS and CT were consistent with portography in 76.6% and 78.4% of examinations, respectively. Cohen's kappa demonstrated that CDUS and CT delivered almost equally reliable results with regard to the portographic gold standard (k = 0.634 [p < 0.001] vs. k = 0.644 [p < 0.001]). In case of findings non-consistent with portography there was no clear trend to over- or underestimation of the degree of thrombosis in both CDUS (60.0% vs. 40.0%) and CT (59.5% vs. 40.5%). CONCLUSIONS: CDUS and CT are equally reliable tools in the radiologic assessment of non-malignant acute splanchnic vein thrombosis.

Chondrogenic Bone Tumors: The Importance of Imaging Characteristics. / Chondrogene Knochentumoren: Bildgebung als Wegweiser?

BACKGROUND: Chondrogenic tumors are the most frequent primary bone tumors. Malignant chondrogenic tumors represent about one quarter of malignant bone tumors. Benign chondrogenic bone tumors are frequent incidental findings at imaging. Radiological parameters may be helpful for identification, characterization, and differential diagnosis. METHODS: Systematic PubMed literature research. Identification and review of studies analyzing and describing imaging characteristics of chondrogenic bone tumors. RESULTS AND CONCLUSIONS: The 2020 World Health Organization (WHO) classification system differentiates between benign, intermediate (locally aggressive or rarely metastasizing), and malignant chondrogenic tumors. On imaging, typical findings of differentiated chondrogenic tumors are lobulated patterns with a high signal on T2-weighted magnetic resonance imaging (MRI) and ring- and arc-like calcifications on conventional radiography and computed tomography (CT). Depending on the entity, the prevalence of this chondrogenic pattern differs. While high grade tumors may be identified due to aggressive imaging patterns, the differentiation between benign and intermediate grade chondrogenic tumors is challenging, even in an interdisciplinary approach. KEY POINTS: · The WHO defines benign, intermediate, and malignant chondrogenic bone tumors. · Frequent benign tumors: osteochondroma and enchondroma; Frequent malignant tumor: conventional chondrosarcoma. · Differentiation between enchondroma versus low-grade chondrosarcoma is challenging for radiologists and pathologists. · Pain, deep scalloping, cortical destruction, bone expansion, soft tissue component: favor chondrosarcoma. · Potential malignant transformation of osteochondroma: progression after skeletal maturity, cartilage cap thickness (> 2 cm adult; > 3 cm child). · Potentially helpful advanced imaging methods: Dynamic MRI, texture analysis, FDG-PET/CT. CITATION FORMAT: · Engel H, Herget GW, Füllgraf H et al. Chondrogenic Bone Tumors: The Importance of Imaging Characteristics. Fortschr Röntgenstr 2021; 193: 262 - 274.

MRI phenotype of the prostate: Transition zone radiomics analysis improves explanation of prostate-specific antigen (PSA) serum level compared to volume measurement alone.

PURPOSE: To determine the value of a radiomics MRI phenotype of the transition zone to explain PSA level in patients with low suspicion for clinically significant cancer to confirm hyperplastic changes. MATERIALS AND METHODS: T2 weighted images from 36 consecutive PI-RADS 2 and 3 cases with volume adapted systematic transperineal biopsy as reference standard (all biopsies negative, 34.8 biopsy cores per patient in average, mean PSA level 10.77 ng/mL) are manually segmented to define transition zone (TZ) volume. 54 radiomic features (RF) are derived for each TZ. RF are tested for significant correlation with PSA level, Bonferroni correction is applied. We build regression models to explain PSA level with a) TZ volume b) RF c) TZ volume+RF. We apply all models to a control group with clinically significant transition zone cancer. RESULTS: TZ volume is moderately correlated with PSA level (r = 0.44). 5/54 RF are significantly correlated with PSA level (r: 0.53-0.69, p < 0.05). Inclusion of each of these five features into the regression model significantly improves the explanatory value for PSA level (p < 0.05). Furthermore, RF alone better explain PSA level compared to TZ volume alone (p < 0.01). A systematic and significant trend for positive residuals is observed when regression models are applied to the malignant control group. CONCLUSION: A radiomics analysis of the transition zone has the potential to improve explanation of corresponding PSA level in patients with low suspicion. This knowledge may reassure radiologists to read prostate MRI cases as unremarkable, despite present hyperplastic changes.

Direct reprogramming of fibroblasts into renal tubular epithelial cells by defined transcription factors.

Direct reprogramming by forced expression of transcription factors can convert one cell type into another. Thus, desired cell types can be generated bypassing pluripotency. However, direct reprogramming towards renal cells remains an unmet challenge. Here, we identify renal cell fate-inducing factors on the basis of their tissue specificity and evolutionarily conserved expression, and demonstrate that combined expression of Emx2, Hnf1b, Hnf4a and Pax8 converts mouse and human fibroblasts into induced renal tubular epithelial cells (iRECs). iRECs exhibit epithelial features, a global gene expression profile resembling their native counterparts, functional properties of differentiated renal tubule cells and sensitivity to nephrotoxic substances. Furthermore, iRECs integrate into kidney organoids and form tubules in decellularized kidneys. Our approach demonstrates that reprogramming factors can be identified by targeted in silico analysis. Renal tubular epithelial cells generated ex vivo by forced expression of transcription factors may facilitate disease modelling, drug and nephrotoxicity testing, and regenerative approaches.

MicroRNAs establish robustness and adaptability of a critical gene network to regulate progenitor fate decisions during cortical neurogenesis.

Over the course of cortical neurogenesis, the transition of progenitors from proliferation to differentiation requires a precise regulation of involved gene networks under varying environmental conditions. In order to identify such regulatory mechanisms, we analyzed microRNA (miRNA) target networks in progenitors during early and late stages of neurogenesis. We found that cyclin D1 is a network hub whose expression is miRNA-dosage sensitive. Experimental validation revealed a feedback regulation between cyclin D1 and its regulating miRNAs miR-20a, miR-20b, and miR-23a. Cyclin D1 induces expression of miR-20a and miR-20b, whereas it represses miR-23a. Inhibition of any of these miRNAs increases the developmental stage-specific mean and dynamic expression range (variance) of cyclin D1 protein in progenitors, leading to reduced neuronal differentiation. Thus, miRNAs establish robustness and stage-specific adaptability to a critical dosage-sensitive gene network during cortical neurogenesis. Understanding such network regulatory mechanisms for key developmental events can provide insights into individual susceptibilities for genetically complex neuropsychiatric disorders.