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Purpose Pancreatic ductal adenocarcinoma (PDAC) is a molecularly heterogeneous tumor entity with no clinically established imaging biomarkers. We hypothesize that tumor morphology and physiology, including vascularity and perfusion, show variations that can be detected by differences in contrast agent (CA) accumulation measured non-invasively. This work seeks to establish imaging biomarkers for tumor stratification and therapy response monitoring in PDAC, based on this hypothesis. Methods and materials Regional CA accumulation in PDAC was correlated with tumor vascularization, stroma content, and tumor cellularity in murine and human subjects. Changes in CA distribution in response to gemcitabine (GEM) were monitored longitudinally with computed tomography (CT) Hounsfield Units ratio (HUr) of tumor to the aorta or with magnetic resonance imaging (MRI) ΔR1 area under the curve at 60 s tumor-to-muscle ratio (AUC60r). Tissue analyses were performed on co-registered samples, including endothelial cell proliferation and cisplatin tissue deposition as a surrogate of chemotherapy delivery. Results Tumor cell poor, stroma-rich regions exhibited high CA accumulation both in human (meanHUr 0.64 vs. 0.34, p < 0.001) and mouse PDAC (meanAUC60r 2.0 vs. 1.1, p < 0.001). Compared to the baseline, in vivo CA accumulation decreased specifically in response to GEM treatment in a subset of human (HUr −18%) and mouse (AUC60r −36%) tumors. Ex vivo analyses of mPDAC showed reduced cisplatin delivery (GEM: 0.92 ± 0.5 mg/g, vs. vehicle: 3.1 ± 1.5 mg/g, p = 0.004) and diminished endothelial cell proliferation (GEM: 22.3% vs. vehicle: 30.9%, p = 0.002) upon GEM administration. Conclusion In PDAC, CA accumulation, which is related to tumor vascularization and perfusion, inversely correlates with tumor cellularity. The standard of care GEM treatment results in decreased CA accumulation, which impedes drug delivery. Further investigation is warranted into potentially detrimental effects of GEM in combinatorial therapy regimens.

In this study, we aim to bridge the gap between the theoretical understanding of attacks against collaborative machine learning workflows and their practical ramifications by considering the effects of model architecture, learning setting and hyperparameters on the resilience against attacks. We refer to such mitigations asmodel adaptation. Through extensive experimentation on both, benchmark and real-life datasets, we establish a more practical threat model for collaborative learning scenarios. In particular, we evaluate the impact of model adaptation by implementing a range of attacks belonging to the broader categories of model inversion and membership inference. Our experiments yield two noteworthy outcomes: they demonstrate the difficulty of actually conducting successful attacks under realistic settings when model adaptation is employed and they highlight the challenge inherent in successfully combining model adaptation and formal privacy-preserving techniques to retain the optimal balance between model utility and attack resilience.

Rationale and Objectives To investigate the effects of a reduced field-of-view (rFOV) acquisition in diffusion-weighted magnetic resonance imaging of the pancreas. Materials and Methods We enrolled 153 patients who underwent routine clinical MRI work-up including respiratory-triggered diffusion-weighted single-shot echo-planar imaging (DWI) with full field-of-view (fFOV, 3 × 3 × 4 mm3 voxel size) and reduced field-of-view (rFOV, 2.5 × 2.5 × 3 mm3 voxel size) for suspected pancreatic pathology. Two experienced radiologists were asked to subjectively rate (Likert Scale 1–4) image quality (overall image quality, lesion conspicuity, anatomical detail, artifacts). In addition, quantitative image parameters were assessed (apparent diffusion coefficient, apparent signal to noise ratio, apparent contrast to noise ratio [CNR]). Results All subjective metrics of image quality were rated in favor of rFOV DWI images compared to fFOV DWI images with substantial-to-high inter-rater reliability. Calculated ADC values of normal pancreas, pancreatic pathologies and reference tissues revealed no differences between both sequences. Whereas the apparent signal to noise ratio was higher in fFOV images, apparent CNR was higher in rFOV images. Conclusion rFOV DWI provides higher image quality and apparent CNR values, favorable in the analysis of pancreatic pathologies.

Artificial Intelligence (AI) has a multitude of applications in cancer research and oncology. However, the training of AI systems is impeded by the limited availability of large datasets due to data protection requirements and other regulatory obstacles. Federated and swarm learning represent possible solutions to this problem by collaboratively training AI models while avoiding data transfer. However, in these decentralized methods, weight updates are still transferred to the aggregation server for merging the models. This leaves the possibility for a breach of data privacy, for example by model inversion or membership inference attacks by untrusted servers. Homomorphically encrypted federated learning (HEFL) is a solution to this problem because only encrypted weights are transferred, and model updates are performed in the encrypted space. Here, we demonstrate the first successful implementation of HEFL in a range of clinically relevant tasks in cancer image analysis on multicentric datasets in radiology and histopathology. We show that HEFL enables the training of AI models which outperform locally trained models and perform on par with models which are centrally trained. In the future, HEFL can enable multiple institutions to co-train AI models without forsaking data governance and without ever transmitting any decryptable data to untrusted servers.One Sentence SummaryFederated learning with homomorphic encryption enables multiple parties to securely co-train artificial intelligence models in pathology and radiology, reaching state-of-the-art performance with privacy guarantees.

The Gaussian mechanism (GM) represents a universally employed tool for achieving differential privacy (DP), and a large body of work has been devoted to its analysis. We argue that the three prevailing interpretations of the GM, namely epsilon/delta-DP, f-DP and Rényi DP can be expressed by using a single parameter psi, which we term the sensitivity index. Psi uniquely characterises the GM and its properties by encapsulating its two fundamental quantities: the sensitivity of the query and the magnitude of the noise perturbation. With strong links to the ROC curve and the hypothesis-testing interpretation of DP, psi offers the practitioner a powerful method for interpreting, comparing and communicating the privacy guarantees of Gaussian mechanisms.

Collaborative machine learning techniques such as federated learning (FL) enable the training of models on effectively larger datasets without data transfer. Recent initiatives have demonstrated that segmentation models trained with FL can achieve performance similar to locally trained models. However, FL is not a fully privacy-preserving technique and privacy-centred attacks can disclose confidential patient data. Thus, supplementing FL with privacy-enhancing technologies (PETs) such as differential privacy (DP) is a requirement for clinical applications in a multi-institutional setting. The application of PETs to FL in medical imaging and the trade-offs between privacy guarantees and model utility, the ramifications on training performance and the susceptibility of the final models to attacks have not yet been conclusively investigated. Here we demonstrate the first application of differentially private gradient descent-based FL on the task of semantic segmentation in computed tomography. We find that high segmentation performance is possible under strong privacy guarantees with an acceptable training time penalty. We furthermore demonstrate the first successful gradient-based model inversion attack on a semantic segmentation model and show that the application of DP prevents it from divulging sensitive image features. Our code is available at https://github.com/TUM-AIMED/PrivateSegmentation.

In this work, we report the set-up and results of the Liver Tumor Segmentation Benchmark (LiTS), which was organized in conjunction with the IEEE International Symposium on Biomedical Imaging (ISBI) 2017 and the International Conferences on Medical Image Computing and Computer-Assisted Intervention (MICCAI) 2017 and 2018. The image dataset is diverse and contains primary and secondary tumors with varied sizes and appearances with various lesion-to-background levels (hyper-/hypo-dense), created in collaboration with seven hospitals and research institutions. Seventy-five submitted liver and liver tumor segmentation algorithms were trained on a set of 131 computed tomography (CT) volumes and were tested on 70 unseen test images acquired from different patients. We found that not a single algorithm performed best for both liver and liver tumors in the three events. The best liver segmentation algorithm achieved a Dice score of 0.963, whereas, for tumor segmentation, the best algorithms achieved Dices scores of 0.674 (ISBI 2017), 0.702 (MICCAI 2017), and 0.739 (MICCAI 2018). Retrospectively, we performed additional analysis on liver tumor detection and revealed that not all top-performing segmentation algorithms worked well for tumor detection. The best liver tumor detection method achieved a lesion-wise recall of 0.458 (ISBI 2017), 0.515 (MICCAI 2017), and 0.554 (MICCAI 2018), indicating the need for further research. LiTS remains an active benchmark and resource for research, e.g., contributing the liver-related segmentation tasks in \url{http://medicaldecathlon.com/}. In addition, both data and online evaluation are accessible via \url{www.lits-challenge.com}., Patrick Bilic, Patrick Christ, Hongwei Bran Li, and Eugene Vorontsov made equal contributions to this work. Published in Medical Image Analysis