James Law | University of Nottingham (original) (raw)

Papers by James Law

Background Obesity and its metabolic consequences are a major cause of morbidity and mortality. B... more Background
Obesity and its metabolic consequences are a major cause of morbidity and mortality. Brown adipose tissue (BAT) utilises glucose and free fatty acids to produce heat, thereby increasing energy expenditure. Effective evaluation of human BAT stimulators is constrained by current standard BAT assessment methods as positron emission tomography-computed tomography (PET-CT) requires exposure to high doses of ionising radiation. Infrared thermography (IRT) is a potential non-invasive, safe alternative, although direct corroboration with PET-CT has not previously been established.
Methods
IRT and 18F-fluorodeoxyglucose (18F-FDG) PET-CT data from 8 healthy male participants subjected to water jacket cooling were directly compared. Thermal images (TIs) were geometrically transformed to overlay PET-CT-derived maximum intensity projection (MIP) images from each subject and the areas of greatest intensity of temperature and glucose-uptake within the supraclavicular regions compared. Relationships between supraclavicular temperatures from IRT (TSCR) and the maximum rate of glucose uptake (MR(gluc)) from PET-CT were determined.
Results
Glucose uptake on MR(gluc)MIP was positively correlated with change in TSCR relative to a reference region (r2 = 0.721; p=0.008). Spatial overlap between areas of maximal MR(gluc)MIP and maximal TSCR was 29.5±5.1%. Prolonged cooling to 60 minutes was associated with further TSCR rise compared with cooling to 10 minutes.
Conclusions
The supraclavicular hotspot identified on IRT closely corresponds to the area of maximal uptake on PET-CT-derived MR(gluc)MIP images. Greater increases in relative TSCR were associated with raised glucose uptake. IRT should now be considered a suitable method for measuring BAT activation, especially in populations where PET-CT is not feasible, practical or repeatable.

Background - The emergence of brown adipose tissue (BAT) as a possible novel obesity prevention a... more Background - The emergence of brown adipose tissue (BAT) as a possible novel obesity prevention and treatment target has led to renewed interest in its physiology. The lack of an acceptable, safe, non-invasive method for repeated analysis is a significant barrier to in vivo human studies as the use of PET-CT in large prospective studies is limited by expense and ionising radiation exposure.We have developed a novel technique for measuring BAT activity using thermal imaging (TI)[1]. TI is a cheap, quick, non-invasive, valid and reproducible procedure acceptable to children as young as five years old[2]. We present here novel modifications to our original method.Method - As previously described[1,2] images centred on the anterior aspect of the neck were obtained using a thermal imaging camera (FLIR B425; FLIR Systems, Sweden) over a 25 minute period, at a rate of 6/minute. Following a period of acclimatisation, the participant's right hand was submerged in cold water (18°C±0.1°C), an effective stimulator of BAT activity[1]. After 10 minutes of stimulation with cold water, each participant removed their hand and imaging was continued for a further 8 minutes.Images were exported using ThermaCAM Researcher Pro 2.10 (FLIR systems) and analysed using a custom-designed code in MATLAB (Mathworks, USA). Key points on each image were identified to define the region of interest (ROI) within which upper temperature percentiles were calculated. Data were exported from MATLAB to Excel 2010 (Microsoft Corporation, USA). Moving averages of order 7 were calculated. A moving average replaces each point with an average of the point and the points on either side, thereby reducing the effect of random fluctuations.Results - Approximately 150 images per participant were captured. Time series were plotted using the original method (Fig 1) compared with the increased image frequency and moving averages (Fig 2).Conclusions - Previous data have shown an increase in the average temperature of the upper percentile of temperature in the region of interest (ROI) over the anterior aspect of the neck with cold water stimulation. Within this, there is a degree of natural variation in measurements. We show here that utilisation of a simple moving average substantially reduces point-to-point fluctuation revealing a clear trend line.By increasing the number of images taken per minute from 1-6, we are able to use higher order moving averages. Previously, the ROI had to be defined for each image using the irregular polygon tool within the ThermaCAM software, which is a time-intensive process. Our new semi-automated process allows larger numbers of images to be processed consistently and quickly. In summary, thermal imaging is an essential tool in the in vivo analysis of BAT, particularly in human participants and the methodological improvements outlined above further improve the method.

Obesity remains a major global health concern. Understanding the metabolic influences of the obes... more Obesity remains a major global health concern. Understanding the metabolic influences of the obesity epidemic in the human population on maintenance of a healthy weight and metabolic profile is still of great significance. The importance and role of white adipose tissue has been long established, particularly with excess adiposity. Brown adipose tissue (BAT), however, has only recently been shown to contribute significantly to the metabolic signature of mammals outside the previously recognised role in small mammals and neonates. BAT’s detection in adults has led to a renewed interest and is now considered to be a potential therapeutic target to prevent excess white fat accumulation in obesity, a theory further promoted by the recent discovery of beige fat. Adipose tissue distribution varies significantly between genders. Pre-menopausal females often show enhanced lower and peripheral fat deposition in adiposity deposition compared to the male profile of central and visceral fat accumulation with obesity. This sex disparity is partly attributed to the different effects of sex hormone profiles and interactions on the adipose tissue system. In this review, we explore this intricate relationship and show how modifications in the effects of sex hormones impact on both brown and white adipose tissues. We also discuss the impact of sex hormones on activation of the hypothalamic-pituitary-adrenal (HPA) axis and how the three pathways between adiposity, HPA and sex steroids can have a major contribution to the prevention or maintenance of obesity and therefore on overall health.

Brown adipose tissue (BAT), present in the supraclavicular region of humans, can be activated by ... more Brown adipose tissue (BAT), present in the supraclavicular region of humans, can be activated by cold stimuli, and even small quantities could result in a large increase in energy expenditure. PET-CT studies have identified more glucose uptake into BAT in winter months. This study was conducted to determine if seasonality had an effect on thermal activity of BAT. Infrared thermography, a technique previously established for this use in children, was used to detect the skin temperature overlying BAT depots in the supraclavicular region. Skin temperatures were recorded in the steady state and 5 minutes after a cool stimulus (hand placed into water at 20°C). The study was conducted at schools in age-matched children aged 8-11 years in the Summer (n=27) and in the Winter (n=25). The interoperator coefficient of variation (CV) (mean 4.11% (range 0.98-9.04%) and intraobserver CV (mean 0.18% (range 0.01-0.38%) were within acceptable limits. In line with our previous published studies, we found that BMI had a significant negative effect on baseline temperature (p<0.001). In addition, baseline skin temperature overlying BAT in the supraclavicular region was significantly greater in Winter (p=0.017, R2=0.31) than Summer independent of BMI, gender, age and room temperature. Future studies of brown adipose tissue activity during daily activities are required to determine possible factors which may be utilised to increase metabolic activity and, therefore, decrease white fat deposition.