Svein Reidar Kjosavik

Alvaro Fernandez-Quilez, Tobias Nordström, Fredrik Jäderling et al.

Background: Prostate cancer (PC) MRI-based risk calculators are commonly based on biological (e.g. PSA), MRI markers (e.g. volume), and patient age. Whilst patient age measures the amount of years an individual has existed, biological age (BA) might better reflect the physiology of an individual. However, surrogates from prostate MRI and linkage with clinically significant PC (csPC) remain to be explored. Purpose: To obtain and evaluate Prostate Age Gap (PAG) as an MRI marker tool for csPC risk. Study type: Retrospective. Population: A total of 7243 prostate MRI slices from 468 participants who had undergone prostate biopsies. A deep learning model was trained on 3223 MRI slices cropped around the gland from 81 low-grade PC (ncsPC, Gleason score <=6) and 131 negative cases and tested on the remaining 256 participants. Assessment: Chronological age was defined as the age of the participant at the time of the visit and used to train the deep learning model to predict the age of the patient. Following, we obtained PAG, defined as the model predicted age minus the patient's chronological age. Multivariate logistic regression models were used to estimate the association through odds ratio (OR) and predictive value of PAG and compared against PSA levels and PI-RADS>=3. Statistical tests: T-test, Mann-Whitney U test, Permutation test and ROC curve analysis. Results: The multivariate adjusted model showed a significant difference in the odds of clinically significant PC (csPC, Gleason score >=7) (OR =3.78, 95% confidence interval (CI):2.32-6.16, P <.001). PAG showed a better predictive ability when compared to PI-RADS>=3 and adjusted by other risk factors, including PSA levels: AUC =0.981 vs AUC =0.704, p<.001. Conclusion: PAG was significantly associated with the risk of clinically significant PC and outperformed other well-established PC risk factors.

Alvaro Fernandez-Quilez, Linas Vidziunas, Ørjan Kløvfjell Thoresen et al.

Traditional deep learning (DL) approaches based on supervised learning paradigms require large amounts of annotated data that are rarely available in the medical domain. Unsupervised Out-of-distribution (OOD) detection is an alternative that requires less annotated data. Further, OOD applications exploit the class skewness commonly present in medical data. Magnetic resonance imaging (MRI) has proven to be useful for prostate cancer (PCa) diagnosis and management, but current DL approaches rely on T2w axial MRI, which suffers from low out-of-plane resolution. We propose a multi-stream approach to accommodate different T2w directions to improve the performance of PCa lesion detection in an OOD approach. We evaluate our approach on a publicly available data-set, obtaining better detection results in terms of AUC when compared to a single direction approach (73.1 vs 82.3). Our results show the potential of OOD approaches for PCa lesion detection based on MRI.

Alvaro Fernandez-Quilez, Christoffer Gabrielsen Andersen, Trygve Eftestøl et al.

Masked Image Modelling (MIM) has been shown to be an efficient self-supervised learning (SSL) pre-training paradigm when paired with transformer architectures and in the presence of a large amount of unlabelled natural images. The combination of the difficulties in accessing and obtaining large amounts of labeled data and the availability of unlabelled data in the medical imaging domain makes MIM an interesting approach to advance deep learning (DL) applications based on 3D medical imaging data. Nevertheless, SSL and, in particular, MIM applications with medical imaging data are rather scarce and there is still uncertainty. around the potential of such a learning paradigm in the medical domain. We study MIM in the context of Prostate Cancer (PCa) lesion classification with T2 weighted (T2w) axial magnetic resonance imaging (MRI) data. In particular, we explore the effect of using MIM when coupled with convolutional neural networks (CNNs) under different conditions such as different masking strategies, obtaining better results in terms of AUC than other pre-training strategies like ImageNet weight initialization.

Sol Erika Boman, Nita Mulliqi, Anders Blilie et al.

Tissue detection is a crucial first step in most digital pathology applications. Details of the segmentation algorithm are rarely reported, and there is a lack of studies investigating the downstream effects of a poor segmentation algorithm. Disregarding tissue detection quality could create a bottleneck for downstream performance and jeopardize patient safety if diagnostically relevant parts of the specimen are excluded from analysis in clinical applications. This study aims to determine whether performance of downstream tasks is sensitive to the tissue detection method, and to compare performance of classical and AI-based tissue detection. To this end, we trained an AI model for Gleason grading of prostate cancer in whole slide images (WSIs) using two different tissue detection algorithms: thresholding (classical) and UNet++ (AI). A total of 33,823 WSIs scanned on five digital pathology scanners were used to train the tissue detection AI model. The downstream Gleason grading algorithm was trained and tested using 70,524 WSIs from 13 clinical sites scanned on 13 different scanners. There was a decrease from 116 (0.43%) to 22 (0.08%) fully undetected tissue samples when switching from thresholding-based tissue detection to AI-based, suggesting an AI model may be more reliable than a classical model for avoiding total failures on slides with unusual appearance. On the slides where tissue could be detected by both algorithms, no significant difference in overall Gleason grading performance was observed. However, tissue detection dependent clinically significant variations in AI grading were observed in 3.5% of malignant slides, highlighting the importance of robust tissue detection for optimal clinical performance of diagnostic AI.

Anders Blilie, Nita Mulliqi, Xiaoyi Ji et al.

Prostate cancer diagnosis heavily relies on histopathological evaluation, which is subject to variability. While immunohistochemical staining (IHC) assists in distinguishing benign from malignant tissue, it involves increased work, higher costs, and diagnostic delays. Artificial intelligence (AI) presents a promising solution to reduce reliance on IHC by accurately classifying atypical glands and borderline morphologies in hematoxylin & eosin (H&E) stained tissue sections. In this study, we evaluated an AI model's ability to minimize IHC use without compromising diagnostic accuracy by retrospectively analyzing prostate core needle biopsies from routine diagnostics at three different pathology sites. These cohorts were composed exclusively of difficult cases where the diagnosing pathologists required IHC to finalize the diagnosis. The AI model demonstrated area under the curve values of 0.951-0.993 for detecting cancer in routine H&E-stained slides. Applying sensitivity-prioritized diagnostic thresholds reduced the need for IHC staining by 44.4%, 42.0%, and 20.7% in the three cohorts investigated, without a single false negative prediction. This AI model shows potential for optimizing IHC use, streamlining decision-making in prostate pathology, and alleviating resource burdens.

Alvaro Fernandez-Quilez, Trygve Eftestøl, Morten Goodwin et al.

Prostate cancer (PCa) is the second most common cancer diagnosed among men worldwide. The current PCa diagnostic pathway comes at the cost of substantial overdiagnosis, leading to unnecessary treatment and further testing. Bi-parametric magnetic resonance imaging (bp-MRI) based on apparent diffusion coefficient maps (ADC) and T2-weighted (T2w) sequences has been proposed as a triage test to differentiate between clinically significant (cS) and non-clinically significant (ncS) prostate lesions. However, analysis of the sequences relies on expertise, requires specialized training, and suffers from inter-observer variability. Deep learning (DL) techniques hold promise in tasks such as classification and detection. Nevertheless, they rely on large amounts of annotated data which is not common in the medical field. In order to palliate such issues, existing works rely on transfer learning (TL) and ImageNet pre-training, which has been proven to be sub-optimal for the medical imaging domain. In this paper, we present a patch-based pre-training strategy to distinguish between cS and ncS lesions which exploit the region of interest (ROI) of the patched source domain to efficiently train a classifier in the full-slice target domain which does not require annotations by making use of transfer learning (TL). We provide a comprehensive comparison between several CNNs architectures and different settings which are presented as a baseline. Moreover, we explore cross-domain TL which exploits both MRI modalities and improves single modality results. Finally, we show how our approaches outperform the standard approaches by a considerable margin

Alvaro Fernandez-Quilez, Steinar Valle Larsen, Morten Goodwin et al.

Whole gland (WG) segmentation of the prostate plays a crucial role in detection, staging and treatment planning of prostate cancer (PCa). Despite promise shown by deep learning (DL) methods, they rely on the availability of a considerable amount of annotated data. Augmentation techniques such as translation and rotation of images present an alternative to increase data availability. Nevertheless, the amount of information provided by the transformed data is limited due to the correlation between the generated data and the original. Based on the recent success of generative adversarial networks (GAN) in producing synthetic images for other domains as well as in the medical domain, we present a pipeline to generate WG segmentation masks and synthesize T2-weighted MRI of the prostate based on a publicly available multi-center dataset. Following, we use the generated data as a form of data augmentation. Results show an improvement in the quality of the WG segmentation when compared to standard augmentation techniques.