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Deep learning for medical image analysis in cancer diagnosis
Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.ORCID iD: 0000-0002-7582-1706
2024 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Medical imaging is one of the cornerstones of clinical diagnosis, providing insights into the anatomy and physiology of organs and tissues for screening, initial diagnosis, treatment planning, and follow-up. Utilizing both invasive and non-invasive techniques, medical imaging employs various contrast mechanisms to capture details of the tissue structure and the functionality of biological systems at different spatial and temporal resolutions, and dimensionalities. The ever-growing volume of medical image data driven by screening programs, digitalization, and the push towards precision medicine has highlighted the need for automatic image analysis methods to reduce the workload of healthcare personnel in reviewing these images.

Deep learning (DL), a subset of artificial intelligence (AI), comprises of methods that learn representations from data to perform various predictive tasks. Although DL was introduced in the mid-1960s, it has only been successfully applied for computer vision tasks in the past two decades, becoming the standard method for natural image processing. Additionally, the versatility of DL in processing data from diverse sources (such as speech, text, and climate) has encouraged its application in the medical domain as well.

This thesis explores the application of DL-based methods for medical image analysis, focusing on cancer diagnosis at various treatment planning stages, including preoperative, intraoperative, and postoperative procedures. Methods were developed and applied to three medical imaging modalities: optical coherence tomography (OCT) for intraoperative diagnosis, magnetic resonance imaging (MRI) for pre-operative diagnosis and radiotherapy treatment planning, and histopathology whole-slide images (WSI) for postoperative final diagnosis, addressing tasks such as detection, semantic segmentation, and classification for thyroid diseases and pediatric and adult brain tumors.

In summary, the outcomes of this thesis highlight the potential of deep learning-based methods for medical image analysis in the context of cancer diagnosis. These works demonstrate the versatility of deep learning in processing medical images from various sources and at different spatial resolutions and dimensionalities. Appropriate dataset curation, method validation and interpretation, and translational research are needed to promote the integration of deep learning-powered tools in the clinic.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2024. , p. 78
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 2408
Keywords [en]
Medical imaging, Cancer diagnosis, Deep learning
National Category
Medical Imaging
Identifiers
URN: urn:nbn:se:liu:diva-208602DOI: 10.3384/9789180757805ISBN: 9789180757799 (print)ISBN: 9789180757805 (electronic)OAI: oai:DiVA.org:liu-208602DiVA, id: diva2:1906440
Public defence
2024-11-27, Belladonna, Building 511, Campus US, Linköping, 09:00 (English)
Opponent
Supervisors
Available from: 2024-10-17 Created: 2024-10-17 Last updated: 2025-02-09Bibliographically approved
List of papers
1. Optical coherence tomography for thyroid pathology: 3D analysis of tissue microstructure
Open this publication in new window or tab >>Optical coherence tomography for thyroid pathology: 3D analysis of tissue microstructure
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2020 (English)In: Biomedical Optics Express, E-ISSN 2156-7085, Vol. 11, no 8, p. 4130-4149, article id 394296Article in journal (Refereed) Published
Abstract [en]

To investigate the potential of optical coherence tomography (OCT) to distinguish between normal and pathologic thyroid tissue, 3D OCT images were acquired on ex vivo thyroid samples from adult subjects (n=22) diagnosed with a variety of pathologies. The follicular structure was analyzed in terms of count, size, density and sphericity. Results showed that OCT images highly agreed with the corresponding histopathology and the calculated parameters were representative of the follicular structure variation. The analysis of OCT volumes provides quantitative information that could make automatic classification possible. Thus, OCT can be beneficial for intraoperative surgical guidance or in the pathology assessment routine.

Place, publisher, year, edition, pages
Optics Info Base, Optical Society of America, 2020
Keywords
Optical Coherence Tomography, Thyroid, Image analysis, Surgery, Pathology
National Category
Other Medical Engineering
Identifiers
urn:nbn:se:liu:diva-167261 (URN)10.1364/BOE.394296 (DOI)000577451600006 ()
Funder
Åke Wiberg Foundation, M19-0455Medical Research Council of Southeast Sweden (FORSS), 471451
Note

Funding agencies: AkeWiberg Stiftelse [M19-0455]; Cancer Organization at Linkoping University; Forskningsradet i Sydostra [FORSS - 471451, FORSS - 563881, FORSS - 755231, FORSS - 931466]

Available from: 2020-07-09 Created: 2020-07-09 Last updated: 2024-10-17
2. Diseased thyroid tissue classification in OCT images using deep learning: towards surgical decision support
Open this publication in new window or tab >>Diseased thyroid tissue classification in OCT images using deep learning: towards surgical decision support
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2023 (English)In: Journal of Biophotonics, ISSN 1864-063X, E-ISSN 1864-0648, E-ISSN 1864-0648, Vol. 16, no 2, article id e202200227Article in journal (Refereed) Published
Abstract [en]

Intraoperative guidance tools for thyroid surgery based on optical coherence tomography (OCT) could aid distinguish between normal and diseased tissue. However, OCT images are difficult to interpret, thus, real-time automatic analysis could support the clinical decision-making. In this study, several deep learning models were investigated for thyroid disease classification on 2D and 3D OCT data obtained from ex vivo specimens of 22 patients undergoing surgery and diagnosed with several thyroid pathologies. Additionally, two open-access datasets were used to evaluate the custom models. On the thyroid dataset, the best performance was achieved by the 3D vision transformer model with a Matthews correlation coefficient (MCC) of 0.79 (accuracy = 0.90) for the normal-versus-abnormal classification. On the open-access datasets, the custom models achieved the best performance (MCC > 0.88, accuracy > 0.96). Results obtained for the normal-versus-abnormal classification suggest OCT, complemented with deep learning-based analysis, as a tool for real-time automatic diseased tissue identification in thyroid surgery.

Keywords
optical coherence tomography, surgical guidance, thyroid, tissue classification, convolutional neural networks, vision transformers
National Category
Medical Engineering Medical Imaging
Identifiers
urn:nbn:se:liu:diva-188559 (URN)10.1002/jbio.202200227 (DOI)000881833000001 ()36203247 (PubMedID)
Funder
Swedish Research Council, 2018-05250Åke Wiberg Foundation, M19-0455,M20-0034, M21-0083Vinnova, 2017-02447 (AIDA))Medical Research Council of Southeast Sweden (FORSS), 931466
Note

Funding: Ake Wiberg Stiftelse [M19-0455 M20-0034 M21-0083]; Forskningsradet i Sydostra Sverige [931466]; VINNOVA via Medtech4Health; AIDA(1908) [2017-02447]; Vetenskapsradet-Swedish Research Council [2018-05250]

Available from: 2022-09-16 Created: 2022-09-16 Last updated: 2025-02-09
3. Inflation of test accuracy due to data leakage in deep learning-based classification of OCT images
Open this publication in new window or tab >>Inflation of test accuracy due to data leakage in deep learning-based classification of OCT images
2022 (English)In: Scientific Data, E-ISSN 2052-4463, Scientific Data, E-ISSN 2052-4463, Vol. 9, no 1, article id 580Article in journal (Refereed) Published
Abstract [en]

In the application of deep learning on optical coherence tomography (OCT) data, it is common to train classification networks using 2D images originating from volumetric data. Given the micrometer resolution of OCT systems, consecutive images are often very similar inboth visible structures and noise. Thus, an inappropriate data split can result in overlap between the training and testing sets, with a largeportion of the literature overlooking this aspect. In this study, the effect of improper dataset splitting on model evaluation is demonstratedfor three classification tasks using three OCT open-access datasets extensively used, Kermany’s and Srinivasan's ophthalmologydatasets, and AIIMS breast tissue dataset. Results show that the classification performance is inflated by 0.07 up to 0.43 in terms ofMatthews Correlation Coefficient (accuracy: 5% to 30%) for models tested on datasets with improper splitting, highlighting theconsiderable effect of dataset handling on model evaluation. This study intends to raise awareness on the importance of dataset splittinggiven the increased research interest in implementing deep learning on OCT data.

Place, publisher, year, edition, pages
Nature Publishing Group, 2022
Keywords
deep learning, artificial intelligence, optical coherence tomography, image
National Category
Medical Imaging
Identifiers
urn:nbn:se:liu:diva-187921 (URN)10.1038/s41597-022-01618-6 (DOI)000857064600001 ()36138025 (PubMedID)
Funder
Medical Research Council of Southeast Sweden (FORSS), 931466Åke Wiberg Foundation, M19-0455, M20-0034, M21-0083Vinnova, 2017-02447Swedish Research Council, 2018-05250Vinnova, ASSIST (2021-01954)
Note

Funding: ITEA/VINNOVA [2021-01954]; Ake Wiberg Stiftelse [M19-0455, M20-0034, M21-0083]; Vinnova project via Medtech4Health and Analytic Imaging Diagnostics Arena (1908) [2017-02447]; Swedish research council [2018-05250];  [FORSS - 931466]

Available from: 2022-08-30 Created: 2022-08-30 Last updated: 2025-02-09
4. Does Anatomical Contextual Information Improve 3D U-Net-Based Brain Tumor Segmentation?
Open this publication in new window or tab >>Does Anatomical Contextual Information Improve 3D U-Net-Based Brain Tumor Segmentation?
2021 (English)In: Diagnostics, ISSN 2075-4418, Diagnostics, ISSN 2075-4418, Vol. 11, no 7, article id 1159Article in journal (Refereed) Published
Abstract [en]

Effective, robust, and automatic tools for brain tumor segmentation are needed for the extraction of information useful in treatment planning. Recently, convolutional neural networks have shown remarkable performance in the identification of tumor regions in magnetic resonance (MR) images. Context-aware artificial intelligence is an emerging concept for the development of deep learning applications for computer-aided medical image analysis. A large portion of the current research is devoted to the development of new network architectures to improve segmentation accuracy by using context-aware mechanisms. In this work, it is investigated whether or not the addition of contextual information from the brain anatomy in the form of white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF) masks and probability maps improves U-Net-based brain tumor segmentation. The BraTS2020 dataset was used to train and test two standard 3D U-Net (nnU-Net) models that, in addition to the conventional MR image modalities, used the anatomical contextual information as extra channels in the form of binary masks (CIM) or probability maps (CIP). For comparison, a baseline model (BLM) that only used the conventional MR image modalities was also trained. The impact of adding contextual information was investigated in terms of overall segmentation accuracy, model training time, domain generalization, and compensation for fewer MR modalities available for each subject. Median (mean) Dice scores of 90.2 (81.9), 90.2 (81.9), and 90.0 (82.1) were obtained on the official BraTS2020 validation dataset (125 subjects) for BLM, CIM, and CIP, respectively. Results show that there is no statistically significant difference when comparing Dice scores between the baseline model and the contextual information models (p > 0.05), even when comparing performances for high and low grade tumors independently. In a few low grade cases where improvement was seen, the number of false positives was reduced. Moreover, no improvements were found when considering model training time or domain generalization. Only in the case of compensation for fewer MR modalities available for each subject did the addition of anatomical contextual information significantly improve (p < 0.05) the segmentation of the whole tumor. In conclusion, there is no overall significant improvement in segmentation performance when using anatomical contextual information in the form of either binary WM, GM, and CSF masks or probability maps as extra channels.

Place, publisher, year, edition, pages
Basel, Switzerland: MDPI, 2021
Keywords
automatic segmentation; artificial intelligence; 3D U-Net; anatomical contextual information; high grade glioma; low grade glioma
National Category
Medical Imaging Cancer and Oncology Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:liu:diva-177355 (URN)10.3390/diagnostics11071159 (DOI)000676813200001 ()
Funder
Swedish Research Council, 2018-05250Åke Wiberg Foundation, M20-0031Linköpings universitet, LiU CancerVinnova, Medtech4Health, AIDA (2017-02447))Vinnova, IMPACT (2018- 02230)
Available from: 2021-06-25 Created: 2021-06-25 Last updated: 2025-02-09Bibliographically approved
5. Deep learning-based detection and identification of brain tumor biomarkers in quantitative MR-images
Open this publication in new window or tab >>Deep learning-based detection and identification of brain tumor biomarkers in quantitative MR-images
2023 (English)In: Machine Learning: Science and Technology, E-ISSN 2632-2153, Vol. 4, no 3, article id 035038Article in journal (Refereed) Published
Abstract [en]

The infiltrative nature of malignant gliomas results in active tumor spreading into the peritumoral edema, which is not visible in conventional magnetic resonance imaging (cMRI) even after contrast injection. MR relaxometry (qMRI) measures relaxation rates dependent on tissue properties, and can offer additional contrast mechanisms to highlight the non-enhancing infiltrative tumor. To investigate if qMRI data provides additional information compared to cMRI sequences when considering deep learning-based brain tumor detection and segmentation, preoperative conventional (T1-w per- and post-contrast, T2-w and FLAIR) and quantitative (pre- and post-contrast R1, R2 and proton density) MR data was obtained from 23 patients with typical radiological findings suggestive of a high-grade malignant glioma. 2D deep learning models were trained on transversal slices (n=528) for tumor detection and segmentation using either conventional or quantitative data. Moreover, trends in quantitative R1 and R2 rates of regions identified as relevant for tumor detection by model explainability methods were qualitatively analyzed. Tumor detection and segmentation performance for models trained with a combination of qMRI pre- and post-contrast was the highest (detection MCC=0.72, segmentation DSC=0.90), however, the difference compared to cMRI was not statistically significant. Overall analysis of the relevant regions identified using model explainability showed no differences between models trained on cMRI or qMRI. When looking at the individual cases, relaxation rates of brain regions outside the annotation and identified as relevant for tumor detection exhibited changes after contrast injection similar to region inside the annotation in the majority of cases. In conclusion, models trained on qMRI data obtained similar detection and segmentation performance to those trained on cMRI data, with the advantage of quantitatively measuring brain tissue properties within similar scan time. When considering individual patients, the analysis of relaxation rates of regions identified by model explainability suggests the presence of infiltrative tumor outside the tumor cMRI-based annotation.

Place, publisher, year, edition, pages
IOP Publishing Ltd, 2023
Keywords
quantitative MRI, brain tumor, deep learning, model explainability, cancer
National Category
Medical Imaging
Identifiers
urn:nbn:se:liu:diva-196603 (URN)10.1088/2632-2153/acf095 (DOI)001058164800001 ()2-s2.0-85170823259 (Scopus ID)
Funder
Swedish Research Council, 2018-05250Vinnova, ASSISTVinnova, IMPACTÅke Wiberg Foundation, M22-0088Medical Research Council of Southeast Sweden (FORSS), FORSS-234551Linköpings universitet, LiU Cancer Strength Area 2021
Note

Funding: CENIIT at Linkoeping University, ITEA3 / VINNOVA funded project Intelligence based iMprovement of Personalized treatment And Clinical workflow supporT (IMPACT); ITEA4 / VINNOVA funded project Automation, Surgery Support and Intuitive 3D visualization to optimize workflow in IGT SysTems (ASSIST) [2021-01954]; Cancer Strength Area at Linkoeping University, VINOVA project via the Analytic Imaging Diagnostics Arena (AIDA) [2017-02447]; Medical Research Council of Southeast Sweden [FORSS-234551]; Swedish Research Council [2018-05250]

Available from: 2023-08-16 Created: 2023-08-16 Last updated: 2025-02-19
6. Pediatric brain tumor classification using deep learning on MR-images with age fusion
Open this publication in new window or tab >>Pediatric brain tumor classification using deep learning on MR-images with age fusion
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2025 (English)In: Neuro-Oncology Advances, E-ISSN 2632-2498, ISSN 2632-2498, Vol. 7, no 1, article id vdae205Article in journal (Refereed) Published
Abstract [en]

Purpose: To implement and evaluate deep learning-based methods for the classification of pediatric brain tumors in MR data.

Materials and methods: A subset of the “Children’s Brain Tumor Network” dataset was retrospectively used (n=178 subjects, female=72, male=102, NA=4, age-range [0.01, 36.49] years) with tumor types being low-grade astrocytoma (n=84), ependymoma (n=32), and medulloblastoma (n=62). T1w post-contrast (n=94 subjects), T2w (n=160 subjects), and ADC (n=66 subjects) MR sequences were used separately. Two deep-learning models were trained on transversal slices showing tumor. Joint fusion was implemented to combine image and age data, and two pre-training paradigms were utilized. Model explainability was investigated using gradient-weighted class activation mapping (Grad-CAM), and the learned feature space was visualized using principal component analysis (PCA).

Results: The highest tumor-type classification performance was achieved when using a vision transformer model pre-trained on ImageNet and fine-tuned on ADC images with age fusion (MCC: 0.77 ± 0.14 Accuracy: 0.87 ± 0.08), followed by models trained on T2w (MCC: 0.58 ± 0.11, Accuracy: 0.73 ± 0.08) and T1w post-contrast (MCC: 0.41 ± 0.11, Accuracy: 0.62 ± 0.08) data. Age fusion marginally improved the model’s performance. Both model architectures performed similarly across the experiments, with no differences between the pre-training strategies. Grad-CAMs showed that the models’ attention focused on the brain region. PCA of the feature space showed greater separation of the tumor-type clusters when using contrastive pre-training.

Conclusion: Classification of pediatric brain tumors on MR-images could be accomplished using deep learning, with the top-performing model being trained on ADC data, which is used by radiologists for the clinical classification of these tumors.

Place, publisher, year, edition, pages
Oxford University Press, 2025
Keywords
deep-learning, artificial intelligence, cancer, pediatric brain tumor, MRI, data fusion
National Category
Medical Imaging Cancer and Oncology Pediatrics
Identifiers
urn:nbn:se:liu:diva-208701 (URN)10.1093/noajnl/vdae205 (DOI)001390014100001 ()39777258 (PubMedID)2-s2.0-85214564318 (Scopus ID)
Funder
Swedish Childhood Cancer Foundation, MT2021-0011, MT2022-0013Linköpings universitet, Cocozza 2022Linköpings universitet, Cancer Strength AreaRegion Östergötland, ALF, 974566
Note

Funding Agencies|Swedish Childhood Cancer Foundation; Children's Brain Tumor Tissue Consortium (CBTTC) / The Children's Brain Tumor Network (CBTN)

Available from: 2024-10-21 Created: 2024-10-21 Last updated: 2025-04-10Bibliographically approved
7. Pediatric brain tumor classification using digital pathology and deep learning: Evaluation of SOTA methods on a multi-center Swedish cohort
Open this publication in new window or tab >>Pediatric brain tumor classification using digital pathology and deep learning: Evaluation of SOTA methods on a multi-center Swedish cohort
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2026 (English)In: Brain Pathology, ISSN 1015-6305, Vol. 36, no 1, article id e70029Article in journal (Refereed) Published
Abstract [en]

Brain tumors are the most common solid tumors in children and young adults, but the scarcity of large histopathology datasets has limited the application of computational pathology in this group. This study implements two weakly supervised multiple-instance learning (MIL) approaches on patch features obtained from state-of-the-art histology-specific foundation models to classify pediatric brain tumors in hematoxylin and eosin whole slide images (WSIs) from a multi-center Swedish cohort. WSIs from 540 subjects (age 8.5 ± 4.9 years) diagnosed with brain tumors were gathered from the six Swedish university hospitals. Instance (patch)-level features were obtained from WSIs using three pre-trained feature extractors: ResNet50, UNI, and CONCH. Instances were aggregated using attention-based MIL (ABMIL) or clustering-constrained attention MIL (CLAM) for patient-level classification. Models were evaluated on three classification tasks based on the hierarchical classification of pediatric brain tumors: tumor category, family, and type. Model generalization was assessed by training on data from two of the centers and testing on data from four other centers. Model interpretability was evaluated through attention mapping. The highest classification performance was achieved using UNI features and ABMIL aggregation, with Matthew's correlation coefficient of 0.76 ± 0.04, 0.63 ± 0.04, and 0.60 ± 0.05 for tumor category, family, and type classification, respectively. When evaluating generalization, models utilizing UNI and CONCH features outperformed those using ResNet50. However, the drop in performance from the in-site to out-of-site testing was similar across feature extractors. These results show the potential of state-of-the-art computational pathology methods in diagnosing pediatric brain tumors at different hierarchical levels with fair generalizability on a multi-center national dataset.

Place, publisher, year, edition, pages
John Wiley & Sons, 2026
Keywords
Deep learning, artificial intelligence, Cancer, Pediatric brain tumor, digital pathology
National Category
Medical Imaging Cancer and Oncology Pediatrics
Identifiers
urn:nbn:se:liu:diva-208705 (URN)10.1111/bpa.70029 (DOI)001519965600001 ()40589103 (PubMedID)2-s2.0-105009437454 (Scopus ID)
Funder
Swedish Childhood Cancer Foundation, MT2021-0011, MT2022-0013Linköpings universitet, Cocozza 2022Linköpings universitet, Cancer Strength AreaVinnova, AIDA (2022-2222)Region Östergötland, ALF, 974566Wallenberg Foundations, Wallenberg Center for Molecular Medicine
Note

Funding Agencies|Linkoeping University's Cancer Strength Area; ALF Grants, Region Ostergoetland [974566]; Vinnova via Medtech4Health and Analytic Imaging Diagnostics Arena [2222]; Swedish Childhood Cancer Fund [MT2021-0011, MT2022-0013]; Joanna Cocozza's Foundation for Children's Medical Research

Available from: 2024-10-21 Created: 2024-10-21 Last updated: 2025-12-18Bibliographically approved

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Tampu, Iulian Emil

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