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Image Segmentation, Registration and Deep Regression: Methods for CT-based Large-Scale Body Composition Analysis
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.ORCID iD: 0000-0003-0202-9205
2025 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Body composition refers to the amount and distribution of fat, muscle, bone, and other tissues in the body. It is associated with the risk of, for example, type 2 diabetes (T2D) and cardiovascular disease (CVD). Computed tomography (CT) is an imaging modality that provides detailed internal views, making it a valuable tool for body composition analysis.

CT imaging, however, exposes the imaged subjects to ionizing radiation, which poses health risks. To mitigate this, limited-slice protocols have been adopted for body composition studies. The Swedish CArdioPulmonary bioImage Study (SCAPIS) and Impaired Glucose Tolerance microbiota study (IGT) cohorts employ a three single-slice CT imaging approach. These cohort studies allow detailed investigations of the relationships between body composition, T2D, and CVD.

The primary aim of this thesis was to develop and evaluate different methods for detailed association studies of CT imaging and non-imaging data, applicable to large-scale body composition research. These methods have been employed to perform tasks such as image segmentation, image registration, voxel-wise association studies, deep regression, and classification.

An automatic segmentation method for the quantification of anatomical structures such as the liver, spleen, skeletal muscle, bone marrow, and various adipose tissue depots based on fully convolutional networks was developed and evaluated. To enable voxel-wise association studies, image registration was performed to align images from different subjects to a common reference space.

Additionally, deep learning-based convolutional neural networks were trained for image-driven regression tasks, predicting proof-of-concept measurements and more complex target variables properties such as age, BMI, and sex. In deep regression tasks, interpretability is important both to validate the model and to aid in the discovery of new associations between the image data and the target variable. To enable interpretability and trustworthiness, individual Gradient-weighted Class Activation Mapping (Grad-CAM) saliency maps were generated, deformed into a common reference space, and subsequently aggregated to produce cohort-level saliency maps. These maps highlight anatomical structures commonly associated with the predicted target (parameter) across the population. Furthermore, uncertainty quantification was employed to provide individual confidence intervals for each prediction, thereby estimating the quality of the model predictions.

In summary, advanced image analysis methods suitable for large-scale body composition analysis have been developed and evaluated. In future research the developed methods can be used, one at a time or in combination, for detailed studies of associations between body composition and, for example, prevalent and incident cardiometabolic diseases and their risk factors.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2025. , p. 78
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 2160
Keywords [en]
computed tomography, body composition, medical image analysis, deep learning, convolutional neural network, image segmentation, image registration, deep regression, saliency analysis, uncertainty quantification
National Category
Radiology and Medical Imaging Medical Imaging
Research subject
Computer Science; Computerized Image Processing; Machine learning
Identifiers
URN: urn:nbn:se:uu:diva-555411ISBN: 978-91-513-2503-3 (print)OAI: oai:DiVA.org:uu-555411DiVA, id: diva2:1954771
Public defence
2025-08-22, H:son Holmdahlsalen, Akademiska sjukhuset, ing. 100, Uppsala, 13:15 (English)
Opponent
Supervisors
Available from: 2025-05-28 Created: 2025-04-27 Last updated: 2025-06-11
List of papers
1. Automatic segmentation of large-scale CT image datasets for detailed body composition analysis.
Open this publication in new window or tab >>Automatic segmentation of large-scale CT image datasets for detailed body composition analysis.
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2023 (English)In: BMC Bioinformatics, E-ISSN 1471-2105, Vol. 24, no 1, article id 346Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Body composition (BC) is an important factor in determining the risk of type 2-diabetes and cardiovascular disease. Computed tomography (CT) is a useful imaging technique for studying BC, however manual segmentation of CT images is time-consuming and subjective. The purpose of this study is to develop and evaluate fully automated segmentation techniques applicable to a 3-slice CT imaging protocol, consisting of single slices at the level of the liver, abdomen, and thigh, allowing detailed analysis of numerous tissues and organs.

METHODS: The study used more than 4000 CT subjects acquired from the large-scale SCAPIS and IGT cohort to train and evaluate four convolutional neural network based architectures: ResUNET, UNET++, Ghost-UNET, and the proposed Ghost-UNET++. The segmentation techniques were developed and evaluated for automated segmentation of the liver, spleen, skeletal muscle, bone marrow, cortical bone, and various adipose tissue depots, including visceral (VAT), intraperitoneal (IPAT), retroperitoneal (RPAT), subcutaneous (SAT), deep (DSAT), and superficial SAT (SSAT), as well as intermuscular adipose tissue (IMAT). The models were trained and validated for each target using tenfold cross-validation and test sets.

RESULTS: The Dice scores on cross validation in SCAPIS were: ResUNET 0.964 (0.909-0.996), UNET++ 0.981 (0.927-0.996), Ghost-UNET 0.961 (0.904-0.991), and Ghost-UNET++ 0.968 (0.910-0.994). All four models showed relatively strong results, however UNET++ had the best performance overall. Ghost-UNET++ performed competitively compared to UNET++ and showed a more computationally efficient approach.

CONCLUSION: Fully automated segmentation techniques can be successfully applied to a 3-slice CT imaging protocol to analyze multiple tissues and organs related to BC. The overall best performance was achieved by UNET++, against which Ghost-UNET++ showed competitive results based on a more computationally efficient approach. The use of fully automated segmentation methods can reduce analysis time and provide objective results in large-scale studies of BC.

Place, publisher, year, edition, pages
BioMed Central (BMC), 2023
Keywords
Body composition, Computed tomography, Deep learning, Medical imaging, Segmentation
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-514086 (URN)10.1186/s12859-023-05462-2 (DOI)001068040700003 ()37723444 (PubMedID)
Available from: 2023-10-13 Created: 2023-10-13 Last updated: 2025-04-27Bibliographically approved
2. Voxel-wise body composition analysis using image registration of a three-slice CT imaging protocol: methodology and proof-of-concept studies
Open this publication in new window or tab >>Voxel-wise body composition analysis using image registration of a three-slice CT imaging protocol: methodology and proof-of-concept studies
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2024 (English)In: Biomedical engineering online, E-ISSN 1475-925X, Vol. 23, no 1, article id 42Article in journal (Refereed) Published
Abstract [en]

Background Computed tomography (CT) is an imaging modality commonly used for studies of internal body structures and very useful for detailed studies of body composition. The aim of this study was to develop and evaluate a fully automatic image registration framework for inter-subject CT slice registration. The aim was also to use the results, in a set of proof-of-concept studies, for voxel-wise statistical body composition analysis (Imiomics) of correlations between imaging and non-imaging data.Methods The current study utilized three single-slice CT images of the liver, abdomen, and thigh from two large cohort studies, SCAPIS and IGT. The image registration method developed and evaluated used both CT images together with image-derived tissue and organ segmentation masks. To evaluate the performance of the registration method, a set of baseline 3-single-slice CT images (from 2780 subjects including 8285 slices) from the SCAPIS and IGT cohorts were registered. Vector magnitude and intensity magnitude error indicating inverse consistency were used for evaluation. Image registration results were further used for voxel-wise analysis of associations between the CT images (as represented by tissue volume from Hounsfield unit and Jacobian determinant) and various explicit measurements of various tissues, fat depots, and organs collected in both cohort studies.Results Our findings demonstrated that the key organs and anatomical structures were registered appropriately. The evaluation parameters of inverse consistency, such as vector magnitude and intensity magnitude error, were on average less than 3 mm and 50 Hounsfield units. The registration followed by Imiomics analysis enabled the examination of associations between various explicit measurements (liver, spleen, abdominal muscle, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), thigh SAT, intermuscular adipose tissue (IMAT), and thigh muscle) and the voxel-wise image information.Conclusion The developed and evaluated framework allows accurate image registrations of the collected three single-slice CT images and enables detailed voxel-wise studies of associations between body composition and associated diseases and risk factors.

Place, publisher, year, edition, pages
Springer Nature, 2024
Keywords
Image registration, Computed tomography, Body composition, Imiomics analysis
National Category
Radiology, Nuclear Medicine and Medical Imaging Medical Imaging
Identifiers
urn:nbn:se:uu:diva-528252 (URN)10.1186/s12938-024-01235-x (DOI)001201490300001 ()38614974 (PubMedID)
Available from: 2024-05-21 Created: 2024-05-21 Last updated: 2025-04-27Bibliographically approved
3. Interpretable Uncertainty-Aware Deep Regression with Cohort Saliency Analysis for Three-Slice CT Imaging Studies
Open this publication in new window or tab >>Interpretable Uncertainty-Aware Deep Regression with Cohort Saliency Analysis for Three-Slice CT Imaging Studies
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2024 (English)In: Proceedings of The 7nd International Conference on Medical Imaging with Deep Learning / [ed] Ninon Burgos; Caroline Petitjean; Maria Vakalopoulou; Stergios Christodoulidis; Pierrick Coupe; Hervé Delingette; Carole Lartizien; Diana Mateus, MLResearchPress , 2024, p. 17-32Conference paper, Published paper (Refereed)
Abstract [en]

Obesity is associated with an increased risk of morbidity and mortality. Achieving a healthy body composition, which involves maintaining a balance between fat and muscle mass, is important for metabolic health and preventing chronic diseases. Computed tomography (CT) imaging offers detailed insights into the body’s internal structure, aiding in understanding body composition and its related factors. In this feasibility study, we utilized CT image data from 2,724 subjects from the large metabolic health cohort studies SCAPIS and IGT. We train and evaluate an uncertainty-aware deep regression based ResNet-50 network, which outputs its prediction as mean and variance, for quantification of cross-sectional areas of liver, visceral adipose tissue (VAT), and thigh muscle. This was done using collages of three single-slice CT images from the liver, abdomen, and thigh regions. The model demonstrated promising results with the evaluation metrics – including R-squared (R2) and mean absolute error (MAE) for predictions. Additionally, for interpretability, the model was evaluated with saliency analysis based on Grad-CAM (Gradient-weighted Class Activation Mapping) at stages 2, 3, and 4 of the network. Deformable image registration to a template subject further enabled cohort saliency analysis that provide group-wise visualization of image regions of importance for associations to biomarkers of interest. We found that the networks focus on relevant regions for each target, according to prior knowledge.

Place, publisher, year, edition, pages
MLResearchPress, 2024
Series
Proceedings of Machine Learning Research, PMLR, E-ISSN 2640-3498 ; 250
National Category
Radiology and Medical Imaging Epidemiology
Research subject
Machine learning
Identifiers
urn:nbn:se:uu:diva-554960 (URN)
Conference
The 7th International Conference on Medical Imaging with Deep Learning, 3-5 July, 2024, Paris, France
Funder
Swedish Research Council, 2019-04756EXODIAB - Excellence of Diabetes Research in SwedenSwedish Heart Lung Foundation
Available from: 2025-04-18 Created: 2025-04-18 Last updated: 2025-06-10Bibliographically approved
4. Interpretable Deep Learning-based Prediction Studies of Body Composition, Age, BMI and Sex from a Three Single-Slice CT Imaging Protocol
Open this publication in new window or tab >>Interpretable Deep Learning-based Prediction Studies of Body Composition, Age, BMI and Sex from a Three Single-Slice CT Imaging Protocol
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(English)Manuscript (preprint) (Other academic)
National Category
Medical and Health Sciences Radiology and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-555403 (URN)
Available from: 2025-04-25 Created: 2025-04-25 Last updated: 2025-04-27

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