Analyse der Körperzusammensetzung: Messung der Skelettmuskulatur mit Computertomographie und Implikationen für die Patientenversorgung

Objective: This thesis aims to evaluate the relationship between the skeletal muscle index derived from computed tomography (CT) images and patient outcomes, as well as its implications for patient care. This goal was pursued in five individual studies: Studies A and B evaluated the relationship between the lumbar skeletal muscle index (L3SMI) and patient outcomes in the intensive care unit (ICU) and oncology setting, respectively. Studies C and D evaluated the effect of CT acquisition parameters on body composition measures. Study E proposed a novel technique to automate the segmentation of skeletal muscle using a fully automated deep learning system. Material and methods: In total, 1328 axial CT images were included in the five studies. Patients in studies A and B were part of the clinical trials NCT01967056 and NCT01401907 at Massachusetts General Hospital (MGH), respectively. Body composition indices were computed using semi-automated segmentation. Multivariable regression models with a priori defined covariates were used to analyze clinical outcomes. To evaluate whether CT acquisition parameters influence segmentation, the Bland-Altman approach was used. In study E, a fully convolutional neural network was implemented for deep learning-based automatic segmentation. Results: Study A found lower L3SMI to be a predictor of increased mortality within 30 days of extubation (p = 0.033), increased rate of pneumonia within 30 days of extubation (p = 0.002), increased adverse discharge disposition (p = 0.044), longer hospital stays post-extubation (p = 0.048), and higher total hospital costs (p = 0.043). In study B, low L3SMI was associated with worse quality of life (p = 0.048) and increased depression symptoms (p = 0.005). Threshold-based segmentation of skeletal muscle in study C and adipose tissue compartments in study D were significantly affected by CT acquisition parameters. The proposed deep learning system in study E provided automatic segmentation of skeletal muscle cross-sectional area and achieved a high congruence to segmentations performed by domain experts (average Dice coefficient of 0.93). Conclusion: L3SMI is a useful tool for the assessment of muscle mass in clinical practice. In critically ill patients, L3SMI can provide clinically useful information about patient outcomes at the time of extubation. Patients with advanced cancer who suffered from low muscle mass reported worse quality of life and increased depression symptoms. This highlights the clinical relevance of addressing muscle loss early on as part of a multimodal treatment plan. Importantly, indices utilized in body composition analysis are significantly affected by CT acquisition parameters. These effects should be considered when body composition analysis is used in clinical practice or research studies. Finally, our fully automated deep learning system enabled instantaneous segmentation of skeletal muscle.Zielsetzung: Das Ziel der vorliegenden Dissertation war es, den Einfluss des auf CT-Bildern berechneten Skelettmuskelindexes auf klinische Ergebnisse von Patienten und die daraus resultierenden Implikationen für die Patientenversorgung zu evaluieren. Dieses Ziel wurde in fünf Einzelstudien verfolgt: In den Studien A und B wurde der Einfluss des lumbalen Skelettmuskelindex (L3SMI) auf klinische Endpunkte von Patienten auf der Intensivstation sowie in der Onkologie untersucht. Die Studien C und D evaluierten die Auswirkungen von CT-Akquisitionsparametern auf Indizes der Körperzusammensetzung. Studie E stellte eine neuartige Technik der automatisierten Segmentierung von Skelettmuskulatur vor, die durch maschinelles Lernen ermöglicht wurde. Material und Methoden: Insgesamt wurden 1328 axiale CT-Bilder in die fünf Studien eingeschlossen. Die Patienten der Studien A und B waren Teilnehmer der klinischen Studien NCT01967056 und NCT01401907 am Massachusetts General Hospital. Die Indizes der Körperzusammensetzung wurden mithilfe halbautomatischer Segmentierung berechnet. Die klinischen Endpunkte wurden in multivariablen Regressionsmodellen mit a priori definierten Kovariaten analysiert. Um zu evaluieren, ob CT-Akquisitionsparameter die Segmentierung beeinflussen, wurde der Bland-Altman-Ansatz verwendet. In Studie E wurden ein künstliches neuronales Netzwerk sowie maschinelles Lernen für die automatische Segmentierung eingesetzt. Ergebnisse: In Studie A war ein niedriger L3SMI ein Prädiktor für eine höhere Mortalität (p = 0.033) und Pneumonierate (p = 0.002) innerhalb von 30 Tagen nach der Extubation sowie für mehr ungünstige Entlassungen (p = 0.044) und höhere Behandlungskosten für den gesamten Krankenhausaufenthalt (p = 0.043). Ein niedriger L3SMI war in Studie B mit einer schlechteren Lebensqualität (p = 0.048) und stärkeren depressiven Symptomen (p = 0.005) assoziiert. Die schwellenwertbasierte Segmentierung der Skelettmuskulatur in Studie C und der Fettgewebekompartimente in Studie D wurde durch CT-Akquisitionsparameter signifikant beeinflusst. Das in Studie E vorgestellte vollautomatische Segmentierungssystem erreichte eine hohe Übereinstimmung mit den durch Experten erstellten Segmentationen (durchschnittlicher Dice-Koeffizient von 0.93). Fazit: Der L3SMI ist ein Werkzeug zur Beurteilung von Muskelmasse. Bei Intensivpatienten kann L3SMI zum Zeitpunkt der Extubation nützliche klinische Informationen liefern. Patienten mit fortgeschrittener Krebserkrankung, die zudem eine geringere Muskelmasse hatten, berichteten über eine schlechtere Lebensqualität und stärkere depressive Symptome. Dies unterstreicht die Notwendigkeit, die Muskulatur frühzeitig als Teil eines multimodalen Behandlungskonzeptes zu adressieren. Die Indizes der Körperzusammensetzung werden signifikant von CT-Akquisitionsparametern beeinflusst. Darüber hinaus ermöglichte unser vollautomatisiertes System dank maschinellen Lernens die verzögerungsfreie Segmentierung von Skelettmuskulatur

Fully-automated Body Composition Analysis in Routine CT Imaging Using 3D Semantic Segmentation Convolutional Neural Networks

Body tissue composition is a long-known biomarker with high diagnostic and prognostic value in cardiovascular, oncological and orthopaedic diseases, but also in rehabilitation medicine or drug dosage. In this study, the aim was to develop a fully automated, reproducible and quantitative 3D volumetry of body tissue composition from standard CT examinations of the abdomen in order to be able to offer such valuable biomarkers as part of routine clinical imaging. Therefore an in-house dataset of 40 CTs for training and 10 CTs for testing were fully annotated on every fifth axial slice with five different semantic body regions: abdominal cavity, bones, muscle, subcutaneous tissue, and thoracic cavity. Multi-resolution U-Net 3D neural networks were employed for segmenting these body regions, followed by subclassifying adipose tissue and muscle using known hounsfield unit limits. The S{\o}rensen Dice scores averaged over all semantic regions was 0.9553 and the intra-class correlation coefficients for subclassified tissues were above 0.99. Our results show that fully-automated body composition analysis on routine CT imaging can provide stable biomarkers across the whole abdomen and not just on L3 slices, which is historically the reference location for analysing body composition in the clinical routine

Artificial intelligence-aided CT segmentation for body composition analysis: a validation study

Background: Body composition is associated with survival outcome in oncological patients, but it is not routinely calculated. Manual segmentation of subcutaneous adipose tissue (SAT) and muscle is time-consuming and therefore limited to a single CT slice. Our goal was to develop an artificial-intelligence (AI)-based method for automated quantification of three-dimensional SAT and muscle volumes from CT images. Methods: Ethical approvals from Gothenburg and Lund Universities were obtained. Convolutional neural networks were trained to segment SAT and muscle using manual segmentations on CT images from a training group of 50 patients. The method was applied to a separate test group of 74 cancer patients, who had two CT studies each with a median interval between the studies of 3 days. Manual segmentations in a single CT slice were used for comparison. The accuracy was measured as overlap between the automated and manual segmentations. Results: The accuracy of the AI method was 0.96 for SAT and 0.94 for muscle. The average differences in volumes were significantly lower than the corresponding differences in areas in a single CT slice: 1.8% versus 5.0% (p < 0.001) for SAT and 1.9% versus 3.9% (p < 0.001) for muscle. The 95% confidence intervals for predicted volumes in an individual subject from the corresponding single CT slice areas were in the order of \ub1 20%. Conclusions: The AI-based tool for quantification of SAT and muscle volumes showed high accuracy and reproducibility and provided a body composition analysis that is more relevant than manual analysis of a single CT slice

Advanced body composition assessment: from body mass index to body composition profiling

This paper gives a brief overview of common non-invasive techniques for body composition analysis and a more in-depth review of a body composition assessment method based on fatreferenced quantitative MRI. Earlier published studies of this method are summarized, and a previously unpublished validation study, based on 4753 subjects from the UK Biobank imaging cohort, comparing the quantitative MRI method with dualenergy X-ray absorptiometry (DXA) is presented. For whole-body measurements of adipose tissue (AT) or fat and lean tissue (LT), DXA and quantitative MRIs show excellent agreement with linear correlation of 0.99 and 0.97, and coefficient of variation (CV) of 4.5 and 4.6 per cent for fat (computed from AT) and LT, respectively, but the agreement was found significantly lower for visceral adipose tissue, with a CV of >20 per cent. The additional ability of MRI to also measure muscle volumes, muscle AT infiltration and ectopic fat, in combination with rapid scanning protocols and efficient image analysis tools, makes quantitative MRI a powerful tool for advanced body composition assessment

Body composition assessment: comparison of quantitative values between magnetic resonance imaging and computed tomography.

Background The primary objective of this study was to compare measurements of skeletal muscle index (SMI), visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) at the level of L3, on subjects who underwent computed tomography (CT) and magnetic resonance imaging (MRI) examinations within a three-month period. The secondary objective was to compare the automatic and semi-automatic quantifications of the same values for CT images. Methods Among subjects who underwent CT and MRI at our Institution between 2011 and 2020, exclusion criteria were: presence of extensive artifacts; images not including the whole waist circumference; CT acquired with low-dose technique and lack of non-contrast images. A set of three axial images (CT, MRI T1-weighted and T2-weighted) were used to extract the following measurements with semi-automatic segmentations: SMI [calculated normalizing skeletal muscle area (SMA) by the square height], SAT, VAT. For the CT images only, the same values were also calculated by using automatic segmentation. Statistical analysis was performed comparing quantitative MRI and CT measurements by Pearson correlation analysis and by Bland-Altman agreement analysis. Results A total of 123 patients were included. By performing linear regression analysis, CT and MRI measurements of SMI showed a high correlation (r2=0.81 for T1, r2=0.89 for T2), with a mean logarithmic difference between CT and MRI quantitative values of 0.041 for T1-weighted and 0.072 for T2-weighted images. CT and MRI measurements of SAT showed high correlation (r2=0.81 for T1; r2=0.81 for T2), with a mean logarithmic difference between CT and MRI values of 0.0174 for T1-weighted and 0.201 for T2-weighted images. CT and MRI measurements of VAT showed high correlation (r2=0.94 for T1; r2=0.93 for T2), with a mean logarithmic difference of 0.040 for T1-weighted and -0.084 for T2-weighted images. The comparison of values extracted by semi-automatic and automatic segmentations were highly correlated. Conclusions Quantification of body composition values at MRI from T1-weighted and T2-weighted images was highly correlated to same values at CT, therefore quantitative values of body composition among patients who underwent either one of the examinations may be compared. CT body composition values extracted by semi-automatic and automatic segmentations showed high correlation

Fully-Automated Analysis of Body Composition from CT in Cancer Patients Using Convolutional Neural Networks

The amounts of muscle and fat in a person's body, known as body composition, are correlated with cancer risks, cancer survival, and cardiovascular risk. The current gold standard for measuring body composition requires time-consuming manual segmentation of CT images by an expert reader. In this work, we describe a two-step process to fully automate the analysis of CT body composition using a DenseNet to select the CT slice and U-Net to perform segmentation. We train and test our methods on independent cohorts. Our results show Dice scores (0.95-0.98) and correlation coefficients (R=0.99) that are favorable compared to human readers. These results suggest that fully automated body composition analysis is feasible, which could enable both clinical use and large-scale population studies

Fully Automated Segmentation and Quantification of Abdominal Adipose Tissue Compartments in Mouse MRI

Obesity currently affects 25% of Canadians and is strongly associated with many diseases including diabetes, cardiovascular disease, and cancer. However, only Intra-Abdominal Adipose Tissue (IAAT) is an important predictor of obesity associated disease and mortality. Magnetic Resonance Imaging (MRI) is an effective modality for imaging fat and methods have been developed to automate segmentation of IAAT. Currently existing techniques for automated segmentation in mice require acquisition using high magnetic field MRI equipment and use image acquisition techniques with low precision for fat quantification. We demonstrate a new fully automated technique for fat quantification in clinical strength mouse MRI through adaptation of an existing human fat quantification technique. We validated this method using images collected from mice in a 3 T clinical MRI against manual segmentation. Dice correlation coefficients revealed that 84% of voxels agreed for Subcutaneous Adipose Tissue (SAT) and 87% of voxels agreed for IAAT

Quantitative body shape analysis for obesity evaluation

Obesity is a public health concern as it is associated with a number of diseases, such as diabetes mellitus type 2, cardiovascular disease, some forms of renal failure and certain types of cancers. Growing evidence suggests that it is not only the amount of fat, but also its distribution in the body that is important to predict metabolic risk factors and adverse changes in organs. In this respect, it is necessary to develop convenient and inexpensive measures to characterize human body fat distribution and to investigate the unknown linkage between intrinsic adiposity and external body shape. This dissertation research aims to improve the obesity assessment by developing new quantitative measurements that comprehensively characterize body shape, and are highly relevant to intrinsic abdominal adiposity conditions. The proposed body shape descriptors were defined based on three-dimensional body images reconstructed from a custom-made stereovision body imaging system, which is particularly suitable for clinical use as an obesity monitoring equipment for its high portability and affordability. In this study, we developed a fully-automated algorithm to process T1-weighted magnetic resonance imaging (MRI) slices for abdominal adiposity measurements. This algorithm dramatically reduces the processing time and workload compared with traditional manual or semi-automatic methods for MRI processing, and greatly improves the repeatability and objectivity of fat assessments. A new obesity categorization method was then defined based on MRI adiposity data to depict characteristics of abdominal fat distribution, and the associations between the body shape descriptors and the MRI abdominal adiposity were explored. It was shown that the proposed body shape descriptors are able to capture the body shape differences between the subjects with dissimilar internal fat distribution (i.e., different categories), and to provide excellent prediction for the category of fat distribution through an optimized support-vector-machine classifier. The predictive models established in this dissertation demonstrate that the novel body shape descriptors were also effective for prediction of the volumes of abdominal visceral fat and subcutaneous fat accumulated in male and female adults. This dissertation introduces an innovative approach to assess obesity and fat distribution based on newly defined shape descriptors, and provides new findings that reveal the associations of intrinsic fat distribution with external body shapes, which enable both qualitative and quantitative assessment of obesity from body shape measurements.Biomedical Engineerin