Fritz Albregtsen

About

My research is mainly focused on medical image analysis. The primary aim is to provide robust prognosis for human cancers, using quantitative image analysis. This work is done together with Master- and PhD-students and colleagues at the Norwegian Radium Hospital. Input data are digital microscopy images of cell nuclei from clinical patient materials covering a number of cancer types. Here we try to find compact and reliable sets of superior textural features for human cancer prognosis within a high-dimensional set of possible feature candidates, thus facilitating a more focused and better treatment of cancer patients.

Selected publications

• Scientific articles and book chapters
• Skrede, Ole-Johan; Pradhan, Manohar; Isaksen, Maria; Hveem, Tarjei Sveinsgjerd; Vlatkovic, Ljiljana & Nesbakken, Arild [Show all 23 contributors for this article] (2026). Generalisation of automatic tumour segmentation in histopathological whole-slide images across multiple cancer types. NPJ precision oncology. 10. doi: 10.1038/s41698-026-01311-6. Full text in Research Archive Show summary Deep learning is expected to aid pathologists in tasks such as tumour segmentation. We developed a general tumour segmentation model for histopathological images and examined its performance in different cancer types. The model was developed using over 20,000 whole-slide images from over 4000 patients with colorectal, endometrial, lung, or prostate carcinoma. Performance was validated in pre-planned analyses on external cohorts with over 3000 patients across six cancer types. Exploratory analyses included over 1500 additional patients from The Cancer Genome Atlas. Average Dice coefficient was over 80% in all validation cohorts with en bloc resection specimens and in The Cancer Genome Atlas cohorts. No performance loss was observed when comparing the general model with single-cancer models specialised in cancer types from the development set. In conclusion, extensive and rigorous evaluations demonstrate that generic tumour segmentation by a single model is possible across cancer types, patient populations, sample preparations and slide scanners.
• Nainamalai, Varatharajan; Prasad, Pravda Jith Ray; Pelanis, Egidijus; Edwin, Bjørn von Gohren; Albregtsen, Fritz & Elle, Ole Jakob [Show all 7 contributors for this article] (2022). Evaluation of clinical applicability of automated liver parenchyma segmentation of multi-center magnetic resonance images. European Journal of Radiology Open (EJR Open). 9. doi: 10.1016/j.ejro.2022.100448. Full text in Research Archive
• Prasad, Pravda Jith Ray; Survarachakan, Shanmugapriya; Khan, Zohaib Amjad; Lindseth, Frank; Elle, Ole Jacob & Albregtsen, Fritz [Show all 7 contributors for this article] (2021). Numerical evaluation on parametric choices influencing segmentation results in radiology images—a multi-dataset study. Electronics (Basel). 10:431(4), p. 1–25. doi: 10.3390/electronics10040431. Full text in Research Archive Show summary Medical image segmentation has gained greater attention over the past decade, especially in the field of image-guided surgery. Here, robust, accurate and fast segmentation tools are important for planning and navigation. In this work, we explore the Convolutional Neural Network (CNN) based approaches for multi-dataset segmentation from CT examinations. We hypothesize that selection of certain parameters in the network architecture design critically influence the segmentation results. We have employed two different CNN architectures, 3D-UNet and VGG-16, given that both networks are well accepted in the medical domain for segmentation tasks. In order to understand the efficiency of different parameter choices, we have adopted two different approaches. The first one combines different weight initialization schemes with different activation functions, whereas the second approach combines different weight initialization methods with a set of loss functions and optimizers. For evaluation, the 3D-UNet was trained with the Medical Segmentation Decathlon dataset and VGG-16 using LiTS data. The quality assessment done using eight quantitative metrics enhances the probability of using our proposed strategies for enhancing the segmentation results. Following a systematic approach in the evaluation of the results, we propose a few strategies that can be adopted for obtaining good segmentation results. Both of the architectures used in this work were selected on the basis of general acceptance in segmentation tasks for medical images based on their promising results compared to other state-of-the art networks. The highest Dice score obtained in 3D-UNet for the liver, pancreas and cardiac data was 0.897, 0.691 and 0.892. In the case of VGG-16, it was solely developed to work with liver data and delivered a Dice score of 0.921. From all the experiments conducted, we observed that two of the combinations with Xavier weight initialization (also known as Glorot), Adam optimiser, Cross Entropy loss (GloAdamCE) and LeCun weight initialization, cross entropy loss and Adam optimiser LecAdamCE worked best for most of the metrics in a 3D-UNet setting, while Xavier together with cross entropy loss and Tanh activation function (GlotanhCE) worked best for the VGG-16 network. Here, the parameter combinations are proposed on the basis of their contributions in obtaining optimal outcomes in segmentation evaluations. Moreover, we discuss that the preliminary evaluation results show that these parameters could later on be used for gaining more insights into model convergence and optimal solutions.The results from the quality assessment metrics and the statistical analysis validate our conclusions and we propose that the presented work can be used as a guide in choosing parameters for the best possible segmentation results for future works.
• Skrede, Ole-Johan; Raedt, Sepp De; Kleppe, Andreas; Hveem, Tarjei Sveinsgjerd; Liestøl, Knut & Maddison, John [Show all 20 contributors for this article] (2020). Deep learning for prediction of colorectal cancer outcome: a discovery and validation study. The Lancet. ISSN 0140-6736. 395:10221, p. 350–360. doi: 10.1016/S0140-6736(19)32998-8. Full text in Research Archive Show summary Background Improved markers of prognosis are needed to stratify patients with early-stage colorectal cancer to refine selection of adjuvant therapy. The aim of the present study was to develop a biomarker of patient outcome after primary colorectal cancer resection by directly analysing scanned conventional haematoxylin and eosin stained sections using deep learning. Methods More than 12 000 000 image tiles from patients with a distinctly good or poor disease outcome from four cohorts were used to train a total of ten convolutional neural networks, purpose-built for classifying supersized heterogeneous images. A prognostic biomarker integrating the ten networks was determined using patients with a non-distinct outcome. The marker was tested on 920 patients with slides prepared in the UK, and then independently validated according to a predefined protocol in 1122 patients treated with single-agent capecitabine using slides prepared in Norway. All cohorts included only patients with resectable tumours, and a formalin-fixed, paraffin-embedded tumour tissue block available for analysis. The primary outcome was cancer-specific survival. Findings 828 patients from four cohorts had a distinct outcome and were used as a training cohort to obtain clear ground truth. 1645 patients had a non-distinct outcome and were used for tuning. The biomarker provided a hazard ratio for poor versus good prognosis of 3·84 (95% CI 2·72–5·43; p<0·0001) in the primary analysis of the validation cohort, and 3·04 (2·07–4·47; p<0·0001) after adjusting for established prognostic markers significant in univariable analyses of the same cohort, which were pN stage, pT stage, lymphatic invasion, and venous vascular invasion. Interpretation A clinically useful prognostic marker was developed using deep learning allied to digital scanning of conventional haematoxylin and eosin stained tumour tissue sections. The assay has been extensively evaluated in large, independent patient populations, correlates with and outperforms established molecular and morphological prognostic markers, and gives consistent results across tumour and nodal stage. The biomarker stratified stage II and III patients into sufficiently distinct prognostic groups that potentially could be used to guide selection of adjuvant treatment by avoiding therapy in very low risk groups and identifying patients who would benefit from more intensive treatment regimes.
• Kleppe, Andreas; Albregtsen, Fritz; Trovik, Jone; Kristensen, Gunnar S Balle & Danielsen, Håvard Emil (2020). Prognostic value of the diversity of nuclear chromatin compartments in gynaecological carcinomas. Cancers. 12:3838(12), p. 1–16. doi: 10.3390/cancers12123838. Full text in Research Archive Show summary Statistical texture analysis of cancer cell nuclei stained for DNA has recently been used to develop a pan-cancer prognostic marker of chromatin heterogeneity. In this study, we instead analysed chromatin organisation by automatically quantifying the diversity of chromatin compartments in cancer cell nuclei. The aim was to investigate the prognostic value of such an assessment in relation to chromatin heterogeneity and as a potential supplement to pathological risk classifications in gynaecological carcinomas. The diversity was quantified by calculating the entropy of both chromatin compartment sizes and optical densities within compartments. We analysed a median of 281 nuclei (interquartile range (IQR), 273 to 289) from 246 ovarian carcinoma patients and a median of 997 nuclei (IQR, 502 to 1452) from 791 endometrial carcinoma patients. The prognostic value of the entropies and chromatin heterogeneity was moderately strongly correlated (r ranged from 0.68 to 0.73), but the novel marker was observed to provide additional prognostic information. In multivariable analysis with clinical and pathological markers, the hazard ratio associated with the novel marker was 2.1 (95% CI, 1.3 to 3.5) in ovarian carcinoma and 2.4 (95% CI, 1.5 to 3.9) in endometrial carcinoma. Integration with pathological risk classifications gave three risk groups with distinctly different prognoses. This suggests that the novel marker of diversity of chromatin compartments might possibly contribute to the selection of high-risk stage I ovarian carcinoma patients for adjuvant chemotherapy and low-risk endometrial carcinoma patients for less extensive surgery.
• Nielsen, Birgitte; Kleppe, Andreas; Hveem, Tarjei Sveinsgjerd; Pradhan, Manohar; Syvertsen, Rolf Anders & Nesheim, John Arne [Show all 11 contributors for this article] (2018). Association Between Proportion of Nuclei With High Chromatin Entropy and Prognosis in Gynecological Cancers. Journal of the National Cancer Institute. ISSN 0027-8874. 110(12), p. 1400–1408. doi: 10.1093/jnci/djy063. Full text in Research Archive Show summary Background: Nuclear texture analysis measuring differences in chromatin structure has provided prognostic biomarkers in several cancers. There is a need for improved cell-by-cell chromatin analysis to detect nuclei with highly disorganized chromatin. The purpose of this study was to develop a method for detecting nuclei with high chromatin entropy and to evaluate the association between the presence of such deviating nuclei and prognosis. Methods: A new texture-based biomarker that characterizes each cancer based on the proportion of high–chromatin entropy nuclei (<25% vs ≥25%) was developed on a discovery set of 175 uterine sarcomas. The prognostic impact of this biomarker was evaluated on a validation set of 179 uterine sarcomas, as well as on independent validation sets of 246 early-stage ovarian carcinomas and 791 endometrial carcinomas. More than 1 million images of nuclei stained for DNA were included in the study. All statistical tests were two-sided. Results: An increased proportion of high–chromatin entropy nuclei was associated with poor clinical outcome. The biomarker predicted five-year overall survival for uterine sarcoma patients with a hazard ratio (HR) of 2.02 (95% confidence interval [CI] = 1.43 to 2.84), time to recurrence for ovarian cancer patients (HR = 2.91, 95% CI = 1.74 to 4.88), and cancer-specific survival for endometrial cancer patients (HR = 3.74, 95% CI = 2.24 to 6.24). Chromatin entropy was an independent prognostic marker in multivariable analyses with clinicopathological parameters (HR = 1.81, 95% CI = 1.21 to 2.70, for sarcoma; HR = 1.71, 95% CI = 1.01 to 2.90, for ovarian cancer; and HR = 2.03, 95% CI = 1.19 to 3.45, for endometrial cancer). Conclusions: A novel method detected high–chromatin entropy nuclei, and an increased proportion of such nuclei was associated with poor prognosis. Chromatin entropy supplemented existing prognostic markers in multivariable analyses of three gynecological cancer cohorts.
• Kleppe, Andreas; Albregtsen, Fritz; Vlatkovic, Ljiljana; Pradhan, Manohar; Nielsen, Birgitte & Hveem, Tarjei Sveinsgjerd [Show all 16 contributors for this article] (2018). Chromatin organisation and cancer prognosis: a pan-cancer study. The Lancet Oncology. ISSN 1470-2045. 19(3), p. 356–369. doi: 10.1016/S1470-2045(17)30899-9. Full text in Research Archive Show summary Background: Chromatin organisation affects gene expression and regional mutation frequencies and contributes to carcinogenesis. Aberrant organisation of DNA has been correlated with cancer prognosis in analyses of the chromatin component of tumour cell nuclei using image texture analysis. As yet, the methodology has not been sufficiently validated to permit its clinical application. We aimed to define and validate a novel prognostic biomarker for the automatic detection of heterogeneous chromatin organisation. Methods Machine learning algorithms analysed the chromatin organisation in 461 000 images of tumour cell nuclei stained for DNA from 390 patients (discovery cohort) treated for stage I or II colorectal cancer at the Aker University Hospital (Oslo, Norway). The resulting marker of chromatin heterogeneity, termed Nucleotyping, was subsequently independently validated in six patient cohorts: 442 patients with stage I or II colorectal cancer in the Gloucester Colorectal Cancer Study (UK); 391 patients with stage II colorectal cancer in the QUASAR 2 trial; 246 patients with stage I ovarian carcinoma; 354 patients with uterine sarcoma; 307 patients with prostate carcinoma; and 791 patients with endometrial carcinoma. The primary outcome was cancer-specific survival. Findings: In all patient cohorts, patients with chromatin heterogeneous tumours had worse cancer-specific survival than patients with chromatin homogeneous tumours (univariable analysis hazard ratio [HR] 1·7, 95% CI 1·2–2·5, in the discovery cohort; 1·8, 1·0–3·0, in the Gloucester validation cohort; 2·2, 1·1–4·5, in the QUASAR 2 validation cohort; 3·1, 1·9–5·0, in the ovarian carcinoma cohort; 2·5, 1·8–3·4, in the uterine sarcoma cohort; 2·3, 1·2–4·6, in the prostate carcinoma cohort; and 4·3, 2·8–6·8, in the endometrial carcinoma cohort). After adjusting for established prognostic patient characteristics in multivariable analyses, Nucleotyping was prognostic in all cohorts except for the prostate carcinoma cohort (HR 1·7, 95% CI 1·1–2·5, in the discovery cohort; 1·9, 1·1–3·2, in the Gloucester validation cohort; 2·6, 1·2–5·6, in the QUASAR 2 cohort; 1·8, 1·1–3·0, for ovarian carcinoma; 1·6, 1·0–2·4, for uterine sarcoma; 1·43, 0·68–2·99, for prostate carcinoma; and 1·9, 1·1–3·1, for endometrial carcinoma). Chromatin heterogeneity was a significant predictor of cancer-specific survival in microsatellite unstable (HR 2·9, 95% CI 1·0–8·4) and microsatellite stable (1·8, 1·2–2·7) stage II colorectal cancer, but microsatellite instability was not a significant predictor of outcome in chromatin homogeneous (1·3, 0·7–2·4) or chromatin heterogeneous (0·8, 0·3–2·0) stage II colorectal cancer. Interpretation: The consistent prognostic prediction of Nucleotyping in different biological and technical circumstances suggests that the marker of chromatin heterogeneity can be reliably assessed in routine clinical practice and could be used to objectively assist decision making in a range of clinical settings. An immediate application would be to identify high-risk patients with stage II colorectal cancer who might have greater absolute benefit from adjuvant chemotherapy. Clinical trials are warranted to evaluate the survival benefit and cost-effectiveness of using Nucleotyping to guide treatment decisions in multiple clinical settings.