Improving the accuracy of fatty liver index to reflect liver fat content with predictive regression modelling

The fatty liver index (FLI) is frequently used as a non-invasive clinical marker for research, prognostic and diagnostic purposes. It is also used to stratify individuals with hepatic steatosis such as non-alcoholic fatty liver disease (NAFLD), and to detect the presence of type 2 diabetes or cardiovascular disease. The FLI is calculated using a combination of anthropometric and blood biochemical variables; however, it reportedly excludes 8.5-16.7% of individuals with NAFLD. Moreover, the FLI cannot quantitatively predict liver fat, which might otherwise render an improved diagnosis and assessment of fatty liver, particularly in longitudinal studies. We propose FLI+ using predictive regression modelling, an improved index reflecting liver fat content that integrates 12 routinely-measured variables, including the original FLI. Methods and findings: We evaluated FLI+ on a dataset from the UK Biobank containing 28,796 individual estimates of proton density fat fraction derived from magnetic resonance imaging across normal to severe levels and interpolated to align with the original FLI range. The results obtained for FLI+ outperform the original FLI by delivering a lower mean absolute error by approximately 47%, a lower standard deviation by approximately 20%, and an increased adjusted R2 statistic by approximately 49%, reflecting a more accurate representation of liver fat content. Conclusions: Our proposed model predicting FLI+ has the potential to improve diagnosis and provide a more accurate stratification than FLI between absent, mild, moderate and severe levels of hepatic steatosis

Automated Measurement of Pancreatic Fat and Iron Concentration Using Multi-Echo and T1-Weghted MRI Data

We present an automated method for estimation of proton density fat fraction and iron concentration in the pancreas using both structural and quantitative imaging data present in the UK Biobank abdominal MRI acquisition protocol. Our method relies on automatic segmentation of 3D T1-weighted MRI data using a convolutional neural network and extracting the location of the multi-echo slice through the segmented volume. We finally estimate the fat and iron content in the pancreas using the extracted segmentation as a mask on the multi-echo data. Our segmentation model achieves a mean dice similarity coefficient of 0.842±0.071 on unseen data, which is comparable to the current state of the art for 3D segmentation of the pancreas. The proposed method is efficient and robust and enables an enhanced analysis of spatial distribution of proton density fat fraction and iron concentration over the current practice of manually placing regions of interest on often ambiguous multi-echo data

Liver Shape Analysis using Statistical Parametric Maps at Population Scale

Background: Morphometric image analysis enables the quantification of differences in the shape and size of organs between individuals. Methods: Here we have applied morphometric methods to the study of the liver by constructing surface meshes from liver segmentations from abdominal MRI images in 33,434 participants in the UK Biobank. Based on these three dimensional mesh vertices, we evaluated local shape variations and modelled their association with anthropometric, phenotypic and clinical conditions, including liver disease and type-2 diabetes. Results: We found that age, body mass index, hepatic fat and iron content, as well as, health traits were significantly associated with regional liver shape and size. Interaction models in groups with specific clinical conditions showed that the presence of type-2 diabetes accelerates age-related changes in the liver, while presence of liver fat further increased shape variations in both type-2 diabetes and liver disease. Conclusions: The results suggest that this novel approach may greatly benefit studies aiming at better categorisation of pathologies associated with acute and chronic clinical conditions

Mass Univariate Regression Analysis for Three-Dimensional Liver Image-Derived Phenotypes

Image-derived phenotypes of abdominal organs from magnetic resonance imaging reveal variations in volume and shape and may be used to model changes in a normal versus pathological organ and improve diagnosis. Computational atlases of anatomical organs provide many advantages in quantifying and modeling differences in shape and size of organs for population imaging studies. Here we made use of liver segmentations derived from Dixon MRI for 2,730 UK Biobank participants to create 3D liver meshes. We computed the signed distances between a reference and subject-specific meshes to define the surface-to-surface (S2S) phenotype. We employed mass univariate regression analysis to compare the S2S values from the liver meshes to image-derived phenotypes specific to the liver, such as proton density fat fraction and iron concentration while adjusting for age, sex, ethnicity, body mass index and waist-to-hip ratio. Vertex-based associations in the 3D liver mesh were extracted and threshold-free cluster enhancement was applied to improve the sensitivity and stability of the statistical parametric maps. Our findings show that the 3D liver meshes are a robust method for modeling the association between anatomical, anthropometric, and phenotypic variations across the liver. This approach may be readily applied to different clinical conditions as well as extended to other abdominal organs in a larger population

Large‑scale analysis of iliopsoas muscle volumes in the UK Biobank

Psoas muscle measurements are frequently used as markers of sarcopenia and predictors of health. Manually measured cross-sectional areas are most commonly used, but there is a lack of consistency regarding the position of the measurement and manual annotations are not practical for large population studies. We have developed a fully automated method to measure iliopsoas muscle volume (comprised of the psoas and iliacus muscles) using a convolutional neural network. Magnetic resonance images were obtained from the UK Biobank for 5000 participants, balanced for age, gender and BMI. Ninety manual annotations were available for model training and validation. The model showed excellent performance against out-of-sample data (average dice score coefficient of 0.9046 ± 0.0058 for six-fold cross-validation). Iliopsoas muscle volumes were successfully measured in all 5000 participants. Iliopsoas volume was greater in male compared with female subjects. There was a small but significant asymmetry between left and right iliopsoas muscle volumes. We also found that iliopsoas volume was significantly related to height, BMI and age, and that there was an acceleration in muscle volume decrease in men with age. Our method provides a robust technique for measuring iliopsoas muscle volume that can be applied to large cohorts

Artifact-Free Fat-Water Separation in Dixon MRI using Deep Learning

Chemical-shift encoded MRI (CSE-MRI) is a widely used technique for the study of body composition and metabolic disorders, where derived fat and water signals enable the quantification of adipose tissue and muscle. The UK Biobank is acquiring whole-body Dixon MRI (a specific implementation of CSE-MRI) for over 100,000 participants. Current processing methods associated with large whole-body volumes are time intensive and prone to artifacts during fat-water separation performed by the scanner, making quantitative analysis challenging. The most common artifacts are fat-water swaps, where the labels are inverted at the voxel level. It is common for researchers to discard swapped data (generally around 10%), which is wasteful and may lead to unintended biases. Given the large number of whole-body Dixon MRI acquisitions in the UK~Biobank, thousands of swaps are expected to be present in the fat and water volumes from image reconstruction performed on the scanner. If they go undetected, errors will propagate into processes such as organ segmentation, and dilute the results in population-based analyses. There is a clear need for a robust method to accurately separate fat and water volumes in big data collections like the UK Biobank. We formulate fat-water separation as a style transfer problem, where swap-free fat and water volumes are predicted from the acquired Dixon MRI data using a conditional generative adversarial network, and introduce a new loss function for the generator model. Our method is able to predict highly accurate fat and water volumes free from artifacts in the UK Biobank. We show that our model separates fat and water volumes using either single input (in-phase only) or dual input (in-phase and opposed-phase) data, with the latter producing superior results. Our proposed method enables faster and more accurate downstream analysis of body composition from Dixon MRI in population studies by eliminating the need for visual inspection or discarding data due to fat-water swaps

Abdominal imaging associates body composition with COVID-19 severity

The main drivers of COVID-19 disease severity and the impact of COVID-19 on long-term health after recovery are yet to be fully understood. Medical imaging studies investigating COVID-19 to date have mostly been limited to small datasets and post-hoc analyses of severe cases. The UK Biobank recruited recovered SARS-CoV-2 positive individuals (n = 967) and matched controls (n = 913) who were extensively imaged prior to the pandemic and underwent follow-up scanning. In this study, we investigated longitudinal changes in body composition, as well as the associations of pre-pandemic image-derived phenotypes with COVID-19 severity. Our longitudinal analysis, in a population of mostly mild cases, associated a decrease in lung volume with SARS-CoV-2 positivity. We also observed that increased visceral adipose tissue and liver fat, and reduced muscle volume, prior to COVID-19, were associated with COVID-19 disease severity. Finally, we trained a machine classifier with demographic, anthropometric and imaging traits, and showed that visceral fat, liver fat and muscle volume have prognostic value for COVID-19 disease severity beyond the standard demographic and anthropometric measurements. This combination of image-derived phenotypes from abdominal MRI scans and ensemble learning to predict risk may have future clinical utility in identifying populations at-risk for a severe COVID-19 outcome

Precision MRI Phenotyping Enables Detection of Small Changes in Body Composition for Longitudinal Cohorts

Longitudinal studies provide unique insights into the impact of environmental factors and lifespan issues on health and disease.Here we investigate changes in body composition in 3,088 free-living participants, part of the UK Biobank in-depth imagingstudy. All participants underwent neck-to-knee MRI scans at the first imaging visit and after approximately two years (secondimaging visit). Image-derived phenotypes for each participant were extracted using a fully-automated image processing pipeline,including volumes of several tissues and organs: liver, pancreas, spleen, kidneys, total skeletal muscle, iliopsoas muscle,visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (ASAT), as well as fat and iron content in liver, pancreasand spleen. Overall, no significant changes were observed in BMI, body weight, or waist circumference over the scanninginterval, despite some large individual changes. A significant decrease in grip strength was observed, coupled to small, butstatistically significant, decrease in all skeletal muscle measurements. Significant increases in VAT and intermuscular fat in thethighs were also detected in the absence of changes in BMI, waist circumference and ectopic-fat deposition. Adjusting fordisease status at the first imaging visit did not have an additional impact on the changes observed. In summary, we showthat even after a relatively short period of time significant changes in body composition can take place, probably reflecting theobesogenic environment currently inhabited by most of the general population in the United Kingdom

Precision MRI phenotyping of muscle volume and quality at a population scale

Introduction: Magnetic resonance imaging (MRI) enables direct measurements of muscle volume and quality, allowing for an in-depth understanding of their associations with anthropometric traits, and health conditions. However, it is unclear which muscle volume measurements: total muscle volume, regional measurements, measurements of muscle quality: intermuscular adipose tissue (IMAT) or proton density fat fraction (PDFF), are most informative and associate with relevant health conditions such as dynapenia and frailty. Methods: We have measured image-derived phenotypes (IDPs) including total and regional muscle volumes and measures of muscle quality, derived from the neck-to-knee Dixon images in 44,520 UK Biobank participants. We further segmented paraspinal muscle from 2D quantitative MRI to quantify muscle PDFF and iron concentration. We defined dynapenia based on grip strength below sex-specific cut-off points and frailty based on five criteria (weight loss, exhaustion, grip strength, low physical activity and slow walking pace). We used logistic regression to investigate the association between muscle volume and quality measurements and dynapenia and frailty. Results: Muscle volumes were significantly higher in male compared with female participants, even after correcting for height while, IMAT (corrected for muscle volume) and paraspinal muscle PDFF were significantly higher in female compared with male participants. From the overall cohort, 7.6% (N = 3,261) were identified with dynapenia, and 1.1% (N = 455) with frailty. Dynapenia and frailty were positively associated with age and negatively associated with physical activity levels. Additionally, reduced muscle volume and quality measurements were associated with both dynapenia and frailty. In dynapenia, muscle volume IDPs were most informative, particularly total muscle exhibiting odds ratios (OR) of 0.392, while for frailty, muscle quality was found to be most informative, in particular thigh IMAT volume indexed to height squared (OR = 1.396), both with p-values below the Bonferroni-corrected threshold (\u1d45d < 8.8 × 10−5). Conclusions: Our fully automated method enables the quantification of muscle volumes and quality suitable for large population-based studies. For dynapenia, muscle volumes particularly those including greater body coverage such as total muscle are the most informative, whilst, for frailty, markers of muscle quality were the most informative IDPs. These results suggest that different measurements may have varying diagnostic values for different health conditions

Precision MRI phenotyping enables detection of small changes in body composition for longitudinal cohorts

Longitudinal studies provide unique insights into the impact of environmental factors and lifespan issues on health and disease. Here we investigate changes in body composition in 3088 free-living participants, part of the UK Biobank in-depth imaging study. All participants underwent neck-to-knee MRI scans at the first imaging visit and after approximately two years (second imaging visit). Image-derived phenotypes for each participant were extracted using a fully-automated image processing pipeline, including volumes of several tissues and organs: liver, pancreas, spleen, kidneys, total skeletal muscle, iliopsoas muscle, visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue, as well as fat and iron content in liver, pancreas and spleen. Overall, no significant changes were observed in BMI, body weight, or waist circumference over the scanning interval, despite some large individual changes. A significant decrease in grip strength was observed, coupled to small, but statistically significant, decrease in all skeletal muscle measurements. Significant increases in VAT and intermuscular fat in the thighs were also detected in the absence of changes in BMI, waist circumference and ectopic-fat deposition. Adjusting for disease status at the first imaging visit did not have an additional impact on the changes observed. In summary, we show that even after a relatively short period of time significant changes in body composition can take place, probably reflecting the obesogenic environment currently inhabited by most of the general population in the United Kingdom