Prostate cancer risk assessment and avoidance of prostate biopsies using fully automatic deep learning in prostate MRI: comparison to PI-RADS and integration with clinical data in nomograms.

OBJECTIVES: Risk calculators (RCs) improve patient selection for prostate biopsy with clinical/demographic information, recently with prostate MRI using the prostate imaging reporting and data system (PI-RADS). Fully-automated deep learning (DL) analyzes MRI data independently, and has been shown to be on par with clinical radiologists, but has yet to be incorporated into RCs. The goal of this study is to re-assess the diagnostic quality of RCs, the impact of replacing PI-RADS with DL predictions, and potential performance gains by adding DL besides PI-RADS. MATERIAL AND METHODS: One thousand six hundred twenty-seven consecutive examinations from 2014 to 2021 were included in this retrospective single-center study, including 517 exams withheld for RC testing. Board-certified radiologists assessed PI-RADS during clinical routine, then systematic and MRI/Ultrasound-fusion biopsies provided histopathological ground truth for significant prostate cancer (sPC). nnUNet-based DL ensembles were trained on biparametric MRI predicting the presence of sPC lesions (UNet-probability) and a PI-RADS-analogous five-point scale (UNet-Likert). Previously published RCs were validated as is; with PI-RADS substituted by UNet-Likert (UNet-Likert-substituted RC); and with both UNet-probability and PI-RADS (UNet-probability-extended RC). Together with a newly fitted RC using clinical data, PI-RADS and UNet-probability, existing RCs were compared by receiver-operating characteristics, calibration, and decision-curve analysis. RESULTS: Diagnostic performance remained stable for UNet-Likert-substituted RCs. DL contained complementary diagnostic information to PI-RADS. The newly-fitted RC spared 49% [252/517] of biopsies while maintaining the negative predictive value (94%), compared to PI-RADS ≥ 4 cut-off which spared 37% [190/517] (p < 0.001). CONCLUSIONS: Incorporating DL as an independent diagnostic marker for RCs can improve patient stratification before biopsy, as there is complementary information in DL features and clinical PI-RADS assessment. CLINICAL RELEVANCE STATEMENT: For patients with positive prostate screening results, a comprehensive diagnostic workup, including prostate MRI, DL analysis, and individual classification using nomograms can identify patients with minimal prostate cancer risk, as they benefit less from the more invasive biopsy procedure. KEY POINTS: The current MRI-based nomograms result in many negative prostate biopsies. The addition of DL to nomograms with clinical data and PI-RADS improves patient stratification before biopsy. Fully automatic DL can be substituted for PI-RADS without sacrificing the quality of nomogram predictions. Prostate nomograms show cancer detection ability comparable to previous validation studies while being suitable for the addition of DL analysis.

Are T2WI PI-RADS sub-scores of transition zone prostate lesions biased by DWI information? A multi-reader, single-center study.

PURPOSE: According to PI-RADS v2.1, T2-weighted imaging (T2WI) is the dominant sequence for transition zone (TZ) lesions. This study aimed to assess, whether diffusion-weighted imaging (DWI) information influences the assignment of T2WI scores. METHOD: Out of 283 prostate MRI examinations with correlated biopsy results, fourty-four patients were selected retrospectively: first, 22 patients with a TZ lesion with T2WI and DWI scores ≥ 4, to represent lesions with unequivocal suspicion on T2WI and DWI. Second, 22 additional patients with TZ lesions of similar T2WI appearance but with corresponding DWI score ≤ 3 were added as control. Four residents and one board-certified radiologist each performed two assessments of the included patients: First, only T2WI was available (T2-only read); second, both T2WI and DWI sequences were available (biparametric read). Lesion scores were assessed using Wilcoxon signed-rank test, inter-reader agreement using weighted kappa and Kendall's W statistics, and sensitivity/specificity using McNemar test. RESULTS: The T2WI scores were significantly different between the T2-only and biparametric read for 3 out of 4 residents (p ≤ 0.049) but not for the radiologist. The overall PI-RADS scores derived from the two reading sessions differed considerably for 35/220 cases (all readers pooled). Inter-reader agreement was fair for the T2WI and overall PI-RADS scores (mean kappa 0.27-0.30) and moderate for the DWI scores (mean kappa 0.43). CONCLUSIONS: For inexperienced readers, assessment of T2WI is variable and potentially biased by availability of DWI information, which can lead to changes of overall PI-RADS score and consequently clinical management. Assessment of T2WI should be performed before reviewing DWI to ensure non-biased interpretation of TZ lesions in the dominant sequence.

Same-day repeatability and Between-Sequence reproducibility of Mean ADC in PI-RADS lesions.

PURPOSE: This study aimed to assess repeatability after repositioning (inter-scan), intra-rater, inter-rater and inter-sequence variability of mean apparent diffusion coefficient (ADC) measurements in MRI-detected prostate lesions. METHOD: Forty-three patients with suspicion for prostate cancer were included and received a clinical prostate bi-/multiparametric MRI examination with repeat scans of the T2-weighted and two DWI-weighted sequences (ssEPI and rsEPI). Two raters (R1 and R2) performed single-slice, 2D regions of interest (2D-ROIs) and 3D-segmentation-ROIs (3D-ROIs). Mean bias, corresponding limits of agreement (LoA), mean absolute difference, within-subject coefficient of variation (CoV) and repeatability/reproducibility coefficient (RC/RDC) were calculated. Bradley & Blackwood test was used for variance comparison. Linear mixed models (LMM) were used to account for multiple lesions per patient. RESULTS: Inter-scan repeatability, intra-rater and inter-sequence reproducibility analysis of ADC showed no significant bias. 3D-ROIs demonstrated significantly less variability than 2D-ROIs (p < 0.01). Inter-rater comparison demonstrated small significant systematic bias of 57 × 10-6 mm2/s for 3D-ROIs (p < 0.001). Intra-rater RC, with the lowest variation, was 145 and 189 × 10-6 mm2/s for 3D- and 2D-ROIs, respectively. For 3D-ROIs of ssEPI, RCs and RDCs were 190-198 × 10-6 mm2/s for inter-scan, inter-rater and inter-sequence variation. No significant differences were found for inter-scan, inter-rater and inter-sequence variability. CONCLUSIONS: In a single-scanner setting, single-slice ADC measurements showed considerable variation, which may be lowered using 3D-ROIs. For 3D-ROIs, we propose a cut-off of âˆ¼ 200 × 10-6 mm2/s for differences introduced by repositioning, rater or sequence effects. The results suggest that follow-up measurements should be possible by different raters or sequences.

Deep Learning for Automatic Bone Marrow Apparent Diffusion Coefficient Measurements From Whole-Body Magnetic Resonance Imaging in Patients With Multiple Myeloma: A Retrospective Multicenter Study.

OBJECTIVES: Diffusion-weighted magnetic resonance imaging (MRI) is increasingly important in patients with multiple myeloma (MM). The objective of this study was to train and test an algorithm for automatic pelvic bone marrow analysis from whole-body apparent diffusion coefficient (ADC) maps in patients with MM, which automatically segments pelvic bones and subsequently extracts objective, representative ADC measurements from each bone. MATERIALS AND METHODS: In this retrospective multicentric study, 180 MRIs from 54 patients were annotated (semi)manually and used to train an nnU-Net for automatic, individual segmentation of the right hip bone, the left hip bone, and the sacral bone. The quality of the automatic segmentation was evaluated on 15 manually segmented whole-body MRIs from 3 centers using the dice score. In 3 independent test sets from 3 centers, which comprised a total of 312 whole-body MRIs, agreement between automatically extracted mean ADC values from the nnU-Net segmentation and manual ADC measurements from 2 independent radiologists was evaluated. Bland-Altman plots were constructed, and absolute bias, relative bias to mean, limits of agreement, and coefficients of variation were calculated. In 56 patients with newly diagnosed MM who had undergone bone marrow biopsy, ADC measurements were correlated with biopsy results using Spearman correlation. RESULTS: The ADC-nnU-Net achieved automatic segmentations with mean dice scores of 0.92, 0.93, and 0.85 for the right pelvis, the left pelvis, and the sacral bone, whereas the interrater experiment gave mean dice scores of 0.86, 0.86, and 0.77, respectively. The agreement between radiologists' manual ADC measurements and automatic ADC measurements was as follows: the bias between the first reader and the automatic approach was 49 × 10 -6 mm 2 /s, 7 × 10 -6 mm 2 /s, and -58 × 10 -6 mm 2 /s, and the bias between the second reader and the automatic approach was 12 × 10 -6 mm 2 /s, 2 × 10 -6 mm 2 /s, and -66 × 10 -6 mm 2 /s for the right pelvis, the left pelvis, and the sacral bone, respectively. The bias between reader 1 and reader 2 was 40 × 10 -6 mm 2 /s, 8 × 10 -6 mm 2 /s, and 7 × 10 -6 mm 2 /s, and the mean absolute difference between manual readers was 84 × 10 -6 mm 2 /s, 65 × 10 -6 mm 2 /s, and 75 × 10 -6 mm 2 /s. Automatically extracted ADC values significantly correlated with bone marrow plasma cell infiltration ( R = 0.36, P = 0.007). CONCLUSIONS: In this study, a nnU-Net was trained that can automatically segment pelvic bone marrow from whole-body ADC maps in multicentric data sets with a quality comparable to manual segmentations. This approach allows automatic, objective bone marrow ADC measurements, which agree well with manual ADC measurements and can help to overcome interrater variability or nonrepresentative measurements. Automatically extracted ADC values significantly correlate with bone marrow plasma cell infiltration and might be of value for automatic staging, risk stratification, or therapy response assessment.

Quantitative Analysis of DCE and DSC-MRI: From Kinetic Modeling to Deep Learning.

BACKGROUND: Perfusion MRI is a well-established imaging modality with a multitude of applications in oncological and cardiovascular imaging. Clinically used processing methods, while stable and robust, have remained largely unchanged in recent years. Despite promising results from novel methods, their relatively minimal improvement compared to established methods did not generally warrant significant changes to clinical perfusion processing. RESULTS AND CONCLUSION: Machine learning in general and deep learning in particular, which are currently revolutionizing computer-aided diagnosis, may carry the potential to change this situation and truly capture the potential of perfusion imaging. Recent advances in the training of recurrent neural networks make it possible to predict and classify time series data with high accuracy. Combining physics-based tissue models and deep learning, using either physics-informed neural networks or universal differential equations, simplifies the training process and increases the interpretability of the resulting models. Due to their versatility, these methods will potentially be useful in bridging the gap between microvascular architecture and perfusion parameters, akin to MR fingerprinting in structural MR imaging. Still, further research is urgently needed before these methods may be used in clinical practice. KEY POINTS: · Machine learning offers promising methods for processing of perfusion data.. · Recurrent neural networks can classify time series with high accuracy.. · Data augmentation is essentially especially when using small datasets.. CITATION FORMAT: · Rotkopf LT, Zhang KS, Tavakoli AA et al. Quantitative Analysis of DCE and DSC-MRI: From Kinetic Modeling to Deep Learning. Fortschr Röntgenstr 2022; 194: 975 - 982.

Pseudoprospective Paraclinical Interaction of Radiology Residents With a Deep Learning System for Prostate Cancer Detection: Experience, Performance, and Identification of the Need for Intermittent Recalibration.

OBJECTIVES: The aim of this study was to estimate the prospective utility of a previously retrospectively validated convolutional neural network (CNN) for prostate cancer (PC) detection on prostate magnetic resonance imaging (MRI). MATERIALS AND METHODS: The biparametric (T2-weighted and diffusion-weighted) portion of clinical multiparametric prostate MRI from consecutive men included between November 2019 and September 2020 was fully automatically and individually analyzed by a CNN briefly after image acquisition (pseudoprospective design). Radiology residents performed 2 research Prostate Imaging Reporting and Data System (PI-RADS) assessments of the multiparametric dataset independent from clinical reporting (paraclinical design) before and after review of the CNN results and completed a survey. Presence of clinically significant PC was determined by the presence of an International Society of Urological Pathology grade 2 or higher PC on combined targeted and extended systematic transperineal MRI/transrectal ultrasound fusion biopsy. Sensitivities and specificities on a patient and prostate sextant basis were compared using the McNemar test and compared with the receiver operating characteristic (ROC) curve of CNN. Survey results were summarized as absolute counts and percentages. RESULTS: A total of 201 men were included. The CNN achieved an ROC area under the curve of 0.77 on a patient basis. Using PI-RADS ≥3-emulating probability threshold (c3), CNN had a patient-based sensitivity of 81.8% and specificity of 54.8%, not statistically different from the current clinical routine PI-RADS ≥4 assessment at 90.9% and 54.8%, respectively ( P = 0.30/ P = 1.0). In general, residents achieved similar sensitivity and specificity before and after CNN review. On a prostate sextant basis, clinical assessment possessed the highest ROC area under the curve of 0.82, higher than CNN (AUC = 0.76, P = 0.21) and significantly higher than resident performance before and after CNN review (AUC = 0.76 / 0.76, P ≤ 0.03). The resident survey indicated CNN to be helpful and clinically useful. CONCLUSIONS: Pseudoprospective paraclinical integration of fully automated CNN-based detection of suspicious lesions on prostate multiparametric MRI was demonstrated and showed good acceptance among residents, whereas no significant improvement in resident performance was found. General CNN performance was preserved despite an observed shift in CNN calibration, identifying the requirement for continuous quality control and recalibration.

Improvement of PI-RADS-dependent prostate cancer classification by quantitative image assessment using radiomics or mean ADC.

Background Currently, interpretation of prostate MRI is performed qualitatively. Quantitative assessment of the mean apparent diffusion coefficient (mADC) is promising to improve diagnostic accuracy while radiomic machine learning (RML) allows to probe complex parameter spaces to identify the most promising multi-parametric models. We have previously developed quantitative RML and ADC classifiers for prediction of clinically significant prostate cancer (sPC) from prostate MRI, however these have not been combined with radiologist PI-RADS assessment. Purpose To propose and evaluate diagnostic algorithms combining quantitative ADC or RML and qualitative PI-RADS assessment for prediction of sPC. Methods and population The previously published quantitative models (RML and mADC) were utilized to construct four algorithms: 1) Down(ADC) and 2) Down(RML): clinically detected PI-RADS positive prostate lesions (defined as either PI-RADS≥3 or ≥4) were downgraded to MRI negative upon negative quantitative assessment; and 3) Up(ADC) and 4) Up(RML): MRI-negative lesions were upgraded to MRI-positive upon positive assessment of quantitative parameters. Analyses were performed at the individual lesion level and the patient level in 133 consecutive patients with suspicion for clinically significant prostate cancer (sPC, International Society of Urological Pathology (ISUP) grade group≥2), the test set subcohort of a previously published patient population. McNemar test was used to compare differences in sensitivity, specificity and accuracy. Differences between lesions of different prostate zones were assessed using ANOVA. Reduction in false positive assessments was assessed as ratios. Results Compared to clinical assessment at the PI-RADS≥4 cut-off alone, algorithms Down(ADC/RML) improved specificity from 43% to 65% (p = 0.001)/62% (p = 0.003), while sensitivity did not change significantly at 89% compared to 87% (p = 1.0)/89% (unchanged) on the patient level. Reduction of false positive lesions was 50% [26/52] in the PZ and 53% [15/28] in the TZ. Algorithms Up(ADC/RML) led, on a patient basis, to an unfavorable loss of specificity from 43% to 30% (p = 0.039)/32% (p = 0.106), with insignificant increase of sensitivity from 89% to 96%/96% (both p = 1.0). Compared to clinical assessment at the PI-RADS≥3 cut-off alone, similar results were observed for Down(ADC) with significantly increased specificity from 2% to 23% (p < 0.001) and unchanged sensitivity on the lesion level; patient level specificity increased only non-significantly. Conclusion Downgrading PI-RADS≥3 and ≥ 4 lesions based on quantitative mADC measurements or RML classifiers can increase diagnostic accuracy by enhancing specificity and preserving sensitivity for detection of sPC and reduce false positives.

PRAS40 suppresses atherogenesis through inhibition of mTORC1-dependent pro-inflammatory signaling in endothelial cells.

Endothelial pro-inflammatory activation plays a pivotal role in atherosclerosis, and many pro-inflammatory and atherogenic signals converge upon mechanistic target of rapamycin (mTOR). Inhibitors of mTOR complex 1 (mTORC1) reduced atherosclerosis in preclinical studies, but side effects including insulin resistance and dyslipidemia limit their clinical use in this context. Therefore, we investigated PRAS40, a cell type-specific endogenous modulator of mTORC1, as alternative target. Indeed, we previously found PRAS40 gene therapy to improve metabolic profile; however, its function in endothelial cells and its role in atherosclerosis remain unknown. Here we show that PRAS40 negatively regulates endothelial mTORC1 and pro-inflammatory signaling. Knockdown of PRAS40 in endothelial cells promoted TNFα-induced mTORC1 signaling, proliferation, upregulation of inflammatory markers and monocyte recruitment. In contrast, PRAS40-overexpression blocked mTORC1 and all measures of pro-inflammatory signaling. These effects were mimicked by pharmacological mTORC1-inhibition with torin1. In an in vivo model of atherogenic remodeling, mice with induced endothelium-specific PRAS40 deficiency showed enhanced endothelial pro-inflammatory activation as well as increased neointimal hyperplasia and atherosclerotic lesion formation. These data indicate that PRAS40 suppresses atherosclerosis via inhibition of endothelial mTORC1-mediated pro-inflammatory signaling. In conjunction with its favourable effects on metabolic homeostasis, this renders PRAS40 a potential target for the treatment of atherosclerosis.