delmona

• Arous, Delmon; Lie, Jacob Larsen; Edin, Nina Frederike Jeppesen & Malinen, Eirik (2025). Integrating 2D dosimetry and cell survival analysis for predicting local effect in spatially fractionated radiotherapy. Acta Oncologica. ISSN 0284-186X. 64, p. 1465–1472. doi: 10.2340/1651-226x.2025.44599. Full text in Research Archive Show summary

  Background and purpose: Robust methods for analysis and prediction of local cell survival after spatially fractionated radiotherapy (SFRT) in vitro remain limited. We present a methodology integrating spatial dosimetry with colony formation assessment and modelling to improve prediction of SFRT-induced responses. Patient/material and methods: A549 lung cancer cells were irradiated with 220 kV X-rays in three field patterns: open, striped, and dotted. Colony centroid locations were mapped from scanned images of culture flasks. Dose distributions were measured using radiochromic film dosimetry. Digital images with colony locations and dose maps were divided into 1 mm² quadrats. A Poisson regression model was fitted to colony counts per quadrat, incorporating linear-quadratic (LQ) model parameters α and β. A modified LQ (MLQ) model included an additional interaction between dose and nearest distance to a peak region, with parameter δ. Results: The methodology was successfully implemented. LQ fitting across all quadrats and patterns yielded α = 0.254 Gy−¹ and β = 0.039 Gy−², while the MLQ model gave α = 0.249 Gy−¹, β = 0.032 Gy−², and δ = −0.040 Gy−¹ cm−¹. Parameter uncertainty was below 0.5%. The MLQ model showed slightly lower fitting errors than the LQ model, indicating improved predictive accuracy. Interpretation: We introduce a novel analysis pipeline for 2D localization of colonies and SFRT survival modelling in vitro. Findings suggest that distance to peak dose regions significantly influences local SFRT effects. Incorporating this spatial factor via an MLQ model may enhance understanding and prediction of SFRT-induced survival.

• Arous, Delmon; Lie, Jacob Larsen; Håland, Bjørg Vårli; Børsting, Magnus; Edin, Nina Frederike Jeppesen & Malinen, Eirik (2023). 2D mapping of radiation dose and clonogenic survival for accurate assessment of in vitro X-ray GRID irradiation effects. Physics in Medicine and Biology. ISSN 0031-9155. 68:025024(2). doi: 10.1088/1361-6560/acaf20. Full text in Research Archive
• Nattudurai, Ravikumar; Arous, Delmon; Edin, Nina Frederike Jeppesen; Pandey, Anant & Malinen, Eirik (2023). New characterization and evaluation of BaSO<inf>4</inf>: Eu as a thermoluminescent radiation dosimeter. Nuclear Instruments and Methods in Physics Reseach B. ISSN 0168-583X. 541, p. 19–25. doi: 10.1016/j.nimb.2023.05.025. Full text in Research Archive
• Zlygosteva, Olga; Juvkam, Inga; Arous, Delmon; Sitarz, Mateusz; Sørensen, Brita Singers & Ankjærgaard, Christina [Show all 11 contributors for this article] (2023). Acute normal tissue responses in a murine model following fractionated irradiation of the head and neck with protons or X-rays. Acta Oncologica. ISSN 0284-186X. doi: 10.1080/0284186X.2023.2254481. Full text in Research Archive Show summary

  Background The purpose of this study was to investigate acute normal tissue responses in the head and neck region following proton- or X-irradiation of a murine model. Materials and methods Female C57BL/6J mice were irradiated with protons (25 or 60 MeV) or X-rays (100 kV). The radiation field covered the oral cavity and the major salivary glands. For protons, two different treatment plans were used, either with the Bragg Peak in the middle of the mouse (BP) or outside the mouse (transmission mode; TM). Delivered physical doses were 41, 45, and 65 Gy given in 6, 7, and 10 fractions for BP, TM, and X-rays, respectively. Alanine dosimetry was used to assess delivered doses. Oral mucositis and dermatitis were scored using CTC v.2.0-based tables. Saliva was collected at baseline, right after end of irradiation, and at day 35. Results The measured dose distribution for protons (TM) and X-rays was very similar. Oral mucositis appeared earlier, had a higher score and was found in a higher percentage of mice after proton irradiation compared to X-irradiation. Dermatitis, on the other hand, had a similar appearance after protons and X-rays. Compared to controls, saliva production was lower right after termination of proton- and X-irradiation. The BP group demonstrated saliva recovery compared to the TM and X-ray group at day 35. Conclusion With lower delivered doses, proton irradiation resulted in similar skin reactions and increased oral mucositis compared to X-irradiation. This indicates that the relative biological effectiveness of protons for acute tissue responses in the mouse head and neck is greater than the clinical standard of 1.1. Thus, there is a need for further investigations of the biological effect of protons in normal tissues.

• Nattudurai, Ravikumar; Arous, Delmon; Edin, Nina Frederike Jeppesen; Pandey, Anant & Malinen, Eirik (2023). The energy dependence of BaSO<inf>4</inf>: Eu nanophosphors for thermoluminescence dosimetry of orthovoltage X-rays and low energy protons. Radiation Physics and Chemistry. ISSN 0969-806X. 208. doi: 10.1016/j.radphyschem.2023.110928. Full text in Research Archive
• Arous, Delmon; Schrunner, Stefan; Hanson, Ingunn; Edin, Nina Frederike Jeppesen & Malinen, Eirik (2022). Principal component-based image segmentation: a new approach to outline in vitro cell colonies. Computer Methods in Biomechanics and Biomedical Engineering: Imaging and Visualization. ISSN 2168-1163. doi: 10.1080/21681163.2022.2035822. Full text in Research Archive Show summary

  Identification, segmentation and counting of stained in vitro cell colonies play a vital part in biological assays. Automating these tasks by optical scanning of cell dishes and subsequent image processing is not trivial due to challenges with, e.g. background noise and contaminations. Here, we present a machine learning procedure to amend these issues by characterising, extracting and segmenting inquired cell colonies using principal component analysis, k-means clustering and a modified watershed segmentation algorithm to automatically identify visible colonies. The proposed segmentation algorithm was tested on two data sets: a T-47D (proprietary) cell colony and a bacteria (open source) data set. High F1 scores (∼0.90 for T-47D and >0.95 for bacterial images), along with low absolute percentage errors (∼11% for T-47D and <5% for bacterial images), underlined good agreement with ground truth data. Our approach outperformed a recent state-of-the-art method on both data sets, demonstrating the usefulness of the presented algorithm.

• Juvkam, Inga; Zlygosteva, Olga; Arous, Delmon; Galtung, Hilde; Malinen, Eirik & Søland, Tine Merete [Show all 7 contributors for this article] (2022). A preclinical model to investigate normal tissue damage following fractionated radiotherapy to the head and neck. Journal of radiation research. ISSN 0449-3060. p. 1–9. doi: 10.1093/jrr/rrac066. Full text in Research Archive Show summary

  Abstract Radiotherapy (RT) of head and neck (H&amp;N) cancer is known to cause both early- and late-occurring toxicities. To better appraise normal tissue responses and their dependence on treatment parameters such as radiation field and type, as well as dose and fractionation scheme, a preclinical model with relevant endpoints is required. 12-week old female C57BL/6 J mice were irradiated with 100 or 180 kV X-rays to total doses ranging from 30 to 85 Gy, given in 10 fractions over 5 days. The radiation field covered the oral cavity, swallowing structures and salivary glands. Monte Carlo simulations were employed to estimate tissue dose distribution. The follow-up period was 35 days, in order to study the early radiation-induced effects. Baseline and post irradiation investigations included macroscopic and microscopic examinations of the skin, lips, salivary glands and oral mucosa. Saliva sampling was performed to assess the salivary gland function following radiation exposure. A dose dependent radiation dermatitis in the skin was observed for doses above 30 Gy. Oral mucositis in the tongue appeared as ulcerations on the ventral surface of the tongue for doses of 75–85 Gy. The irradiated mice showed significantly reduced saliva production compared to controls. In summary, a preclinical model to investigate a broad panel of normal tissue responses following fractionated irradiation of the H&amp;N region was established. The optimal dose to study early radiation-induced effects was found to be around 75 Gy, as this was the highest tolerated dose that gave acute effects similar to that observed in cancer patients.

• Asperud, Jonas; Arous, Delmon; Edin, Nina Frederike Jeppesen & Malinen, Eirik (2021). Spatially fractionated radiotherapy: Tumor response modelling including immunomodulation. Physics in Medicine and Biology. ISSN 0031-9155. 66(17). doi: 10.1088/1361-6560/ac176b. Full text in Research Archive
• Grigalavicius, Mantas; Mastrangelopoulou, Maria; Arous, Delmon; Juzeniene, Asta; Ménard, Mathilde & Skarpen, Ellen [Show all 8 contributors for this article] (2020). Photodynamic efficacy of cercosporin in 3D tumor cell CCultures. Photochemistry and Photobiology. ISSN 0031-8655. 96(3), p. 699–707. doi: 10.1111/php.13257. Full text in Research Archive Show summary

  In the present work, we study the photodynamic action of cercosporin (cerco), a naturally occurring photosensitizer, on human cancer multicellular spheroids. U87 spheroids exhibit double the uptake of cerco than T47D and T98G spheroids as shown by flow cytometry on the single cell level. Moreover, cerco is efficiently internalized by cells throughout the spheroid as shown by confocal microscopy, for all three cell lines. Despite their higher cerco uptake, U87 spheroids show the least vulnerability to cerco‐PDT, in contrast to the other two cell lines (T47D and T98G). While 300 μm diameter spheroids consistently shrink and become necrotic after cerco PDT, bigger spheroids (>500 μm) start to regrow following blue‐light PDT and exhibit high viability. Cerco‐PDT was found to be effective on bigger spheroids reaching 1mm in diameter especially under longer exposure to yellow light (~590 nm). In terms of metabolism, T47D and T98G undergo a complete bioenergetic collapse (respiration and glycolysis) as a result of cerco‐PDT. U87 spheroids also experienced a respiratory collapse following cerco‐PDT, but retained half their glycolytic activity.

• Grigalavicius, Mantas; Mastrangelopoulou, Maria; Berg, Kristian; Arous, Delmon; Ménard, Mathilde & Henriksen-Raabe, Tine Therese [Show all 12 contributors for this article] (2019). Proton-dynamic therapy following photosensitiser activation by accelerated protons demonstrated through fluorescence and singlet oxygen production. Nature Communications. 10(1). doi: 10.1038/s41467-019-12042-7. Full text in Research Archive Show summary

  We demonstrate excitation of photosensitisers (PSs) by accelerated protons to produce fluorescence and singlet oxygen. Their fluorescence follows a pattern similar to the proton energy loss in matter, while proton-derived fluorescence spectra match the photon-induced spectra. PSs excited in dry gelatin exhibit enhanced phosphorescence, suggesting an efficient PSs triplet state population. Singlet oxygen measurements, both optically at ~1270 nm and through the photoproduct of protoporphyrin IX (PpIX), demonstrate cytotoxic singlet oxygen generation by proton excitation. The singlet oxygen-specific scavenger 1,4-diazabicyclo[2.2.2]octane (DABCO) abrogates the photoproduct formation under proton excitation, but cannot countermand the overall loss of PpIX fluorescence. Furthermore, in two cell lines, M059K and T98G, we observe differential cell death upon the addition of the PS cercosporin, while in U87 cells we see no effect at any proton irradiation dose. Our results pave the way for a novel treatment combining proton therapy and “proton-dynamic therapy” for more efficient tumour eradication.

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• Nattudurai, Ravikumar; Arous, Delmon; Edin, Nina Frederike Jeppesen; Pandey, Anant & Malinen, Eirik (2022). Investigation of BaSO4:Eu nanophosphors for thermoluminescence dosimetry of X-ray and proton beams. Radiotherapy and Oncology. ISSN 0167-8140. 170, p. S1356–S1356. Full text in Research Archive
• Nattudurai, Ravikumar; Arous, Delmon; Edin, Nina Frederike Jeppesen; Pandey, Anant & Malinen, Eirik (2022). Dosimetric characterization of BaSO4 phosphors activated by Eu for proton, gamma and X-ray beams. Full text in Research Archive
• Grigalavicius, Mantas; Mastrangelopoulou, Maria; Berg, K.; Arous, Delmon; Ménard, M. & Raabe-Henriksen, T. [Show all 12 contributors for this article] (2021). Publisher Correction: Proton-dynamic therapy following photosensitiser activation by accelerated protons demonstrated through fluorescence and singlet oxygen production (Nature Communications, (2019), 10, 1, (3986), 10.1038/s41467-019-12042-7). Nature Communications. 12(1). doi: 10.1038/s41467-021-27175-x. Full text in Research Archive
• Nattudurai, Ravikumar; Arous, Delmon; Edin, Nina Frederike Jeppesen & Malinen, Eirik (2021). Estimating linear energy transfer in proton beams using alanine/EPR dosimetry. Full text in Research Archive
• Nattudurai, Ravikumar; Arous, Delmon; Edin, Nina Frederike Jeppesen & Malinen, Eirik (2021). Alanine dosimeters for determining linear energy transfer in proton beams. Radiotherapy and Oncology. ISSN 0167-8140. 161, p. 229–229. Full text in Research Archive

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