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Interpretable Uncertainty-Aware Deep Regression with Cohort Saliency Analysis for Three-Slice CT Imaging Studies
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.ORCID iD: 0000-0003-0202-9205
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.ORCID iD: 0000-0003-0253-9037
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Medical, Mölndal, Sweden.ORCID iD: 0000-0002-5550-3575
Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
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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. p. 17-32
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: urn:nbn:se:uu:diva-554960OAI: oai:DiVA.org:uu-554960DiVA, id: diva2:1953279
Conference
The 7th International Conference on Medical Imaging with Deep Learning, 3-5 July, 2024, Paris, France
Part of project
Large-scale image analysis for studies of causes and consequences of whole body composition, Swedish Research Council
Funder
Swedish Research Council, 2019-04756EXODIAB - Excellence of Diabetes Research in SwedenSwedish Heart Lung FoundationAvailable from: 2025-04-18 Created: 2025-04-18 Last updated: 2025-06-10Bibliographically approved
In thesis
1. Image Segmentation, Registration and Deep Regression: Methods for CT-based Large-Scale Body Composition Analysis
Open this publication in new window or tab >>Image Segmentation, Registration and Deep Regression: Methods for CT-based Large-Scale Body Composition Analysis
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
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:nbn:se:uu:diva-555411 (URN)978-91-513-2503-3 (ISBN)
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

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Ahmad, NoumanÖfverstedt, JohanTarai, SambitAhlström, HåkanKullberg, Joel

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