Brandon Whitcher

University of Westminster · Research Centre for Optimal Health

Objectives: This study aimed to assess the fatty acid (FA) composition of abdominal subcutaneous (ASAT) and visceral (VAT) adipose tissue in the UK Biobank imaging cohort (N = 33,823) using magnetic resonance imaging (MRI). Methods: We measured the fractions of saturated (fSFA), monounsaturated (fMUFA), and polyunsaturated (fPUFA) in ASAT and VAT f...

We aimed to unravel the mechanisms connecting adiposity to type 2 diabetes. We used MR-Clust to cluster independent genetic variants associated with body fat percentage (388 variants) and BMI (540 variants) based on their impact on type 2 diabetes. We identified five clusters of adiposity-increasing alleles associated with higher type 2 diabetes ri...

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:...

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...

Background Organ measurements derived from magnetic resonance imaging (MRI) have the potential to enhance our understanding of the precise phenotypic variations underlying many clinical conditions. Methods We applied morphometric methods to study the kidneys by constructing surface meshes from kidney segmentations from abdominal MRI data in 38,868...

We evaluate the shared genetic regulation of mRNA molecules, proteins and metabolites derived from whole blood from 3029 human donors. We find abundant allelic heterogeneity, where multiple variants regulate a particular molecular phenotype, and pleiotropy, where a single variant associates with multiple molecular phenotypes over multiple genomic r...

Background: Organ measurements derived from magnetic resonance imaging (MRI) have the potential to enhance our understanding of the precise phenotypic variations underlying many clinical conditions. Methods: We applied morphometric methods to study the kidneys by constructing surface meshes from kidney segmentations from abdominal MRI data in 38,86...

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 = 9...

Background 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 measurements: total muscle volume, regional measurements or measurements of muscle quality, such as...

Unlabelled: 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. Cur...

The application of multiple omics technologies in biomedical cohorts has the potential to reveal patient-level disease characteristics and individualized response to treatment. However, the scale and heterogeneous nature of multi-modal data makes integration and inference a non-trivial task. We developed a deep-learning-based framework, multi-omics...

Background In the treatment of type 2 diabetes, GLP-1 receptor agonists lower blood glucose concentrations, body weight, and have cardiovascular benefits. The efficacy and side effects of GLP-1 receptor agonists vary between people. Human pharmacogenomic studies of this inter-individual variation can provide both biological insight into drug action...

Background 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...

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...

MRI measurements of heart volumes and vessel dimensions typically require specialised cardiac MRI examinations, which can be time consuming and resource intensive. Simpler scans covering the heart and major blood vessels of the abdomen may potentially provide useful clinical information. We used deep learning to segment cardiovascular structures fr...

The spleen plays a key role in iron homeostasis. It is the largest filter of the blood and performs iron reuptake from old or damaged erythrocytes. Despite this role, spleen iron concentration has not been measured in a large, population-based cohort. In this study, we quantify spleen iron in 41,764 participants of the UK Biobank by using magnetic...

Aims: Trials investigating the role of carbohydrate restriction in the management of glycaemia in type 2 diabetes (T2D) have been confounded by multiple factors including degree of calorie restriction, dietary protein content, and by no clear definition of a low-carbohydrate diet. The current study sought to provide insight into the relationship b...

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 appro...

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...

Aging, and the pathogenesis of many common diseases, involves iron homeostasis. A key role in iron homeostasis is played by the spleen, which is the largest filter of the blood and performs iron reuptake from old or damaged erythrocytes. Despite this important role, spleen iron content has not been measured previously in a large, population-based c...

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 imaging study. All participants underwent neck-to-knee MRI scans at baseline and after approximately two y...

Dixon MRI is widely used for body composition studies. Current processing methods associated with large whole-body volumes are time intensive and prone to artifacts during fat-water separation performed on the scanner, making the data difficult to analyse. The most common artifact are fat-water swaps, where the labels are inverted at the voxel leve...

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 po...

Cardiometabolic diseases are an increasing global health burden. While socioeconomic, environmental, behavioural, and genetic risk factors have been identified, a better understanding of the underlying mechanisms is required to develop more effective interventions. Magnetic resonance imaging (MRI) has been used to assess organ health, but biobank-s...

The role of carbohydrate restriction in the management of glycemia in type 2 diabetes (T2D) has been a subject of immense debate and controversy partly due to low-carbohydrate trials being confounded by multiple factors including degree of calorie restriction, dietary protein content, and by no clear definition of a low-carbohydrate diet. The curre...

To understand the causal role of adiposity and ectopic fat in type 2 diabetes and cardiometabolic diseases, we aimed to identify two clusters of adiposity genetic variants, one with ‘adverse’ metabolic effects (UFA) and the other with, paradoxically, ‘favourable’ metabolic effects (FA). We performed a multivariate genome-wide association study usin...

Abstract 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 automa...

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 measurementand manual annotations are not practical for large population studies. We have developed a fully automated method...

Cardiometabolic diseases are an increasing population health burden and while several well established socioeconomic, environmental, behavioural, and genetic risk factors have been identified, our understanding of their drivers and mechanisms remains incomplete. Thus, a better understanding of these factors is required for the development of more e...

Visceral adipose tissue (VAT) plays an important role in the pathogenesis of insulin resistance (IR), prediabetes and type 2 diabetes. However, VAT volume alone might not be the best marker for insulin resistance and prediabetes or diabetes, as a given VAT volume may impact differently on these metabolic traits based on body height, gender, age and...

An end-to-end image analysis pipeline is presented for the abdominal MRI protocol used in the UK Biobank on the first 38,971 participants. Emphasis is on the processing steps necessary to ensure a high-level of data quality and consistency is produced in order to prepare the datasets for downstream quantitative analysis, such as segmentation and pa...

Objectives The ATTIS study aimed to investigate whether substituting almonds for typical snacks (high in refined starch, free sugars and saturated fats, and low in fibre) influenced cardiometabolic risk factors. Primary outcomes, endothelial function and liver fat, were measured in healthy adults aged 30–70 y who were habitual snackers and at moder...

Background: There is convincing evidence that daily whole almond consumption lowers blood LDL cholesterol concentrations, but effects on other cardiometabolic risk factors such as endothelial function and liver fat are still to be determined. Objectives: We aimed to investigate whether isoenergetic substitution of whole almonds for control snack...

Type 2 diabetes is more common in non‐Europeans and starts at a younger age and at lower BMI cut‐offs. This review discusses the insights from genetic studies about pathophysiological mechanisms which determine risk of disease with a focus on the role of adiposity and body fat distribution in ethnic disparity in risk of type 2 diabetes. During the...

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 extracti...

The problem of classifying subjects into risk categories is a common challenge in medical research. Machine Learning (ML) methods are widely used in the areas of risk prediction and classification. The primary objective of these algorithms is to predict dichotomous responses (e.g. healthy/at risk) based on several features. Similarly to statistical...

Intrahepatic lipid (IHL) is linked with reduced hepatic insulin sensitivity and insulin clearance. Despite their high risk for type 2 diabetes (T2D), there have been limited investigations of these relationships in Black populations. We investigated these relationships in 18 White European (WE) and 18 Black West African (BWA) men with T2D <5 years....

Objective This study performed individual‐centric, data‐driven calculations of propensity for coronary heart disease (CHD) and type 2 diabetes (T2D), utilizing magnetic resonance imaging‐acquired body composition measurements, for sub‐phenotyping of obesity and nonalcoholic fatty liver disease (NAFLD). Methods A total of 10,019 participants from t...

Neuroconductor (https://neuroconductor.org) is an open-source platform for rapid testing and dissemination of reproducible computational imaging software. The goals of the project are to: (i) provide a centralized repository of R software dedicated to image analysis, (ii) disseminate software updates quickly, (iii) train a large, diverse community...

Intramyocellular lipid and its relationship with insulin sensitivity and fat in type 2 diabetic men of White and Black ethnicity - Volume 76 Issue OCE4 - O. Hakim, G. Charles-Edwards, B. Whitcher, H. Shuaib, L.M. Goff

Associations between regional and whole-body fat and insulin sensitivity in type 2 diabetic men of White and Black ethnicity - Volume 76 Issue OCE4 - O. Hakim, G. Charles-Edwards, B. Whitcher, H. Shuaib, L.M. Goff

Background: T2 -weighted imaging (T2 -WI) information has been used in a qualitative manner in the assessment of prostate cancer. Quantitative derivatives (T2 relaxation time) can be generated from T2 -WI. These outputs may be useful in helping to discriminate clinically significant prostate cancer from background signal. Purpose/hypothesis: To...

Objectives: To investigate changes in the Apparent Diffusion Coefficient (ADC) using diffusion-weighted imaging (DWI) in men on active surveillance for prostate cancer taking dutasteride 0.5 mg or placebo. Methods: We analysed 37 men, randomised to 6 months of daily dutasteride (n = 18) or placebo (n = 19), undergoing 3T multi-parametric Magnetic R...

The aim of this study was to test whether bilinear and nonlinear effective connectivity (EC) measures of working memory fMRI data can differentiate between patients with schizophrenia (SZ) and healthy controls (HC). We applied bilinear and nonlinear Dynamic Causal Modeling (DCM) for the analysis of verbal working memory in 16 SZ and 21 HC. The conn...

Objective To determine if the perfusion parameters by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of regional nodal metastasis are helpful in characterizing nodal status and to understand the relationship with those of primary tumor of nasopharyngeal carcinoma (NPC). Materials and Methods Newly diagnosed patients imaged between...

Objectives: To investigate changes in the Apparent Diffusion Coefficient (ADC) using diffusion-weighted imaging (DWI) in men on active surveillance for prostate cancer taking dutasteride 0.5 mg or placebo. Methods: We analysed 37 men, randomised to 6 months of daily dutasteride (n = 18) or placebo (n = 19), undergoing 3T multi-parametric Magneti...

Purpose: Dutasteride is licensed for symptomatic benign prostatic hyperplasia, and has been associated with a lower progression rate in low-risk prostate cancer. We have evaluated the effect of dutasteride on prostate cancer volume as assessed by T2-weighted Magnetic Resonance Imaging (MRI). Materials and methods: In this randomized, double-blin...

Direct measurements of body composition through magnetic resonance imaging (MRI) can provide a much better description of the population than traditional indirect measurements, such as body mass index (BMI) or waist circumference. Anatomically-specific measurements of fat and muscle have the potential to reduce the duration of clinical studies and...

Rare genetic variants of large effect can help elucidate the pathophysiology of brain disorders. Here we expand the clinical and genetic analyses of a family with a (1;11)(q42;q14.3) translocation multiply affected by major psychiatric illness and test the effect of the translocation on the structure and function of prefrontal, and temporal brain r...

Introduction and aims: Although primarily a lung disease, chronic obstructive pulmonary disease (COPD) is now recognised to have extra-pulmonary effects on distant organs, the “systemic effects” and co-morbidities of COPD. Aim of this study was to quantify vascular inflammation in 20 COPD ex-smokers and 4 healthy controls (non-smokers) using combin...

Introduction: ¹⁸FDG Positron Emission Tomography/Computerised Tomography (PET/CT) imaging may be a useful tool to study lung inflammation in Chronic Obstructive Pulmonary Disease (COPD). Method: The aim of this study was to establish the optimum protocol for ¹⁸FDG-PET/CT imaging of lung inflammation in COPD in combination with quantitative CT analy...

The disrupted in schizophrenia 1 (DISC1) gene locus was originally identified in a Scottish pedigree with a high incidence of psychiatric disorders that is associated with a balanced t(1;11)(q42.1;q14.3) chromosomal translocation. Here, we investigated whether members of this family carrying the t(1;11)(q42.1;q14.3) translocation have a common brai...

Individuals carrying rare, but biologically informative genetic variants provide a unique opportunity to model major mental illness and inform understanding of disease mechanisms. The rarity of such variations means that their study involves small group numbers, however they are amongst the strongest known genetic risk factors for major mental illn...

Introduction 18FDG PET/CT imaging may be a useful tool to study COPD and lung inflammation; however the optimal protocol for this imaging biomarker has yet to be established. Method We aimed to develop a combined 18FDG-PET/CT imaging protocol optimised to quantify lung inflammation. Six patients with moderate-to-severe COPD underwent dynamic 18FDG-...

In this chapter we measure the effect a scheduled event, like the opening or closing of a regional foreign exchange market, or a unscheduled act, such as a market crash, a political upheaval, or a surprise news announcement, has on the foreign exchange rate’s level of volatility and its well documented long-memory behavior. Volatility in the foreig...

PurposeTo propose and evaluate a new automated method for the identification of new/enlarging multiple sclerosis (MS) lesions on subtracted images (SI). The subtraction of serially acquired images has shown great potential in assessing new/enlarging brain magnetic resonance imaging (MRI) lesions in MS patients. However, this approach relies on the...

Objectives: To evaluate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for characterising nasopharyngeal carcinoma (NPC). Methods: Forty-five newly diagnosed NPC patients were recruited. The initial enhancement rate (E R ), contrast transfer rate (k ep ), elimination rate (k el ), maximal enhancement (MaxEn) and initial area unde...

Diffusion imaging is a promising marker of microstructural damage in neurodegenerative disorders, but interpretation of its relationship with underlying neuropathology can be complex. Here, we examined both volumetric and brain microstructure abnormalities in 13 amnestic patients with mild cognitive impairment (MCI), who progressed to probable Alzh...

Objective: To evaluate the percentage change in volume of prostate cancer, as assessed by T2-weighted MRI, following exposure to dutasteride (Avodart) 0.5mg daily for six months. Patients and methods: MRI in Primary Prostate cancer after Exposure to Dutasteride (MAPPED) is a double-blind, placebo-controlled trial, supported by GlaxoSmithKline (G...

Many therapeutic approaches to cancer affect the tumour vasculature, either indirectly or as a direct target. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has become an important means of investigating this action, both pre-clinically and in early stage clinical trials. For such trials, it is essential that the measurement process...

The development of anti-cancer therapies demands new biomarkers in order to assess efficacy. Established measurements that rely on changes in tumor size from a structural acquisition may not be the most appropriate. There is also the desire to move away from manual techniques in favor or more automated analysis methods. The variety of MRI sequences...

Replications of the association between APOE-ε4 allele load and regional brain atrophy in Alzheimer's disease (AD) patients hold promise for future studies testing relationships between other disease risk gene variants and brain structure. A polymorphism, rs10868366, in the Golgi phosphoprotein 2 gene, GOLM1, was recently identified as an AD risk f...

Restless legs syndrome (RLS) is a common neurological disorder the pathophysiology of which is incompletely understood. Four studies have examined structural differences between the brains of RLS patients and healthy controls, using voxel-based morphometry (VBM). All 4 studies have provided different results. Optimized VBM was used to search for st...

The special volume on 'Magnetic Resonance Imaging in R' features articles and packages related to a variety of imaging modalities: functional MRI, diffusion-weighted MRI, dynamic contrast-enhanced MRI, dynamic susceptibility-contrast MRI and structural MRI. The papers describe the methodology, software implementation and provide comprehensive examp...

We investigate the use of Hilbert wavelet pairs (HWPs) in the non-decimated discrete wavelet transform for the time-varying spectral analysis of multivariate time series. HWPs consist of two high-pass and two low-pass compactly supported filters, such that one high-pass filter is the Hilbert transform (approximately) of the other. Thus, common quan...

The package dcemriS4 provides a complete set of data analysis tools for quantitative assessment of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Im-age processing is provided for the ANALYZE and NIfTI data formats as input with all parameter estimates being output in NIfTI format. Estimation of T1 relaxation from multiple flip-ang...

Two packages, oro.dicom and oro.nifti, are provided for the interaction with and manipulation of medical imaging data that conform to the DICOM standard or ANALYZE/NIfTI formats. DICOM data, from a single file or directory tree, may be uploaded into R using basic data structures: a data frame for the header information and a matrix for the image da...

There is limited evidence that imaging biomarkers can predict subsequent response to therapy. Such prognostic and/or predictive biomarkers would facilitate development of personalised medicine. We hypothesised that pre-treatment measurement of the heterogeneity of tumour vascular enhancement could predict clinical outcome following combination anti...

TPS155 Background: In recent years rationally designed targeted molecules have improved progression free survival in selected tumour types. These agents are primarily cytostatic and it is increasingly obvious that ‘conventional’ pharmacodynamic (PD) end points are no longer adequate in evaluating their activity. The incorporation of novel PD biomar...

Pharmacokinetic parameters from dynamic contrast-enhanced MRI (DCE-MRI) were used to assess the perfusion effects due to treatment response using a tyrosine kinase inhibitor. A Bayesian hierarchical model (BHM) is proposed, as an alternative to voxel-wise estimation procedures, to test for a treatment effect while explicitly modeling known sources...

R is a language and environment for statistical computing and graphics. It can be considered an alternative implementation of the S language developed in the 1970s and 1980s for data analysis and graphics (Becker and Chambers, 1984; Becker et al., 1988). The R language is part of the GNU project and offers versions that compile and run on almost ev...

Here we describe methods for application of quantitative fluorodeoxyglucose positron emission tomography ([ 18F]FDG-PET) measures of brain glucose metabolism in multi-centre clinical trials for Alzheimer's disease. We validated methods and demonstrated their use in the context of a treatment trial with the PPARγ agonist Rosiglitazone XR versus plac...

Though mild cognitive impairment is an intermediate clinical state between healthy aging and Alzheimer's disease (AD), there are very few whole-brain voxel-wise diffusion MRI studies directly comparing changes in healthy control, mild cognitive impairment (MCI) and AD subjects. Here we report whole-brain findings from a comprehensive study of diffu...

High angular resolution diffusion imaging data is the observed characteristic function for the local diffusion of water molecules in tissue. This data is used to infer structural information in brain imaging. Nonparametric scalar measures are proposed to summarize such data, and to locally characterize spatial features of the diffusion probability...

Here we report the first multi-center clinical trial in Alzheimer's disease (AD) using fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) measures of brain glucose metabolism as the primary outcome. We contrasted effects of 12 months treatment with the PPARγ agonist Rosiglitazone XR versus placebo in 80 mild to moderate AD patients. Sec...

In this study, we introduce a new technique to model the variation of microstructural parameters across speci c brain regions. We use a simple model of di usion in each voxel, but model the variation of parameters across the region using penalised splines. We t the whole region model directly to the di usion-weighted signals. We test the tech- niqu...

Dynamic contrast-enhanced MRI is becoming a standard tool for imaging-based trials of anti-vascular/angiogenic agents in cancer. So far, however, biomarkers derived from DCE-MRI parameter maps have largely neglected the fact that the maps have spatial structure and instead focussed on distributional summary statistics. Such statistics-e.g., biomark...

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is an important tool for detecting subtle kinetic changes in cancerous tissue. Quantitative analysis of DCE-MRI typically involves the convolution of an arterial input function (AIF) with a nonlinear pharmacokinetic model of the contrast agent concentration. Parameters of the kinetic mo...