Sarah Wayte

Identification of Brown Adipose Tissue Using MR Imaging in a Human Adult With Histological and Immunohistochemical Confirmation

OBJECTIVE Manipulation of human brown adipose tissue (BAT) represents a novel therapeutic option for diabesity. The aim of our study was to develop and test a novel magnetic resonance (MR) imaging-based method to identify human BAT, delineate it from white adipose tissue, and validate it through immunohistochemistry. DESIGN A 25-year old Caucasian female with hyperparathyroidism-jaw tumor syndrome underwent parathyroidectomy. An (18)fluoro-2-deoxyglucose positron emission tomography (PET)-computed tomography (CT) scan performed after surgery ruled out malignancy but showed avid uptake within the mediastinum, neck, supraclavicular fossae, and axillae, consistent with BAT. Immunohistochemical staining using uncoupling protein-1 antibody was performed on one fat sample obtained from the suprasternal area during parathyroidectomy. Subsequently, serial MR scans were performed. Retrospectively, regions of interest (ROIs) were identified on MR corresponding to areas of high uptake on PET-CT. Prospectively, ROIs were identified on MR based on signal intensity and appearance and compared with PET-CT. RESULTS Of 111 retrospectively identified ROIs from PET-CT, 93 (83.8%) showed corresponding low MR signal: 25 of 25 mediastinum (100%), 29 of 31 neck (93.5%), 31 of 41 supraclavicular (75.6%), and 8 of 14 axillae (57%). Prospectively, 47 of 54 ROIs identified on MR (87%) showed a corresponding increased uptake on PET-CT. Serendipitously, the sample obtained at surgery corresponded with high uptake and low signal on subsequent PET and MR, respectively, and immunohistochemistry confirmed BAT. CONCLUSION We provide the first report for the reliable use of MR to identify BAT in a living human adult, with histological/immunohistochemical confirmation. Our data demonstrate proof of concept to support the development of MR as a safe, reproducible imaging modality for human BAT.

Magnetic Resonance investigation into the mechanisms involved in the development of high-altitude cerebral edema

Rapid ascent to high altitude commonly results in acute mountain sickness, and on occasion potentially fatal high-altitude cerebral edema. The exact pathophysiological mechanisms behind these syndromes remain to be determined. We report a study in which 12 subjects were exposed to a FiO2 = 0.12 for 22 h and underwent serial magnetic resonance imaging sequences to enable measurement of middle cerebral artery velocity, flow and diameter, and brain parenchymal, cerebrospinal fluid and cerebral venous volumes. Ten subjects completed 22 h and most developed symptoms of acute mountain sickness (mean Lake Louise Score 5.4; p < 0.001 vs. baseline). Cerebral oxygen delivery was maintained by an increase in middle cerebral artery velocity and diameter (first 6 h). There appeared to be venocompression at the level of the small, deep cerebral veins (116 cm3 at 2 h to 97 cm3 at 22 h; p < 0.05). Brain white matter volume increased over the 22-h period (574 ml to 587 ml; p < 0.001) and correlated with cumulative Lake Louise scores at 22 h (p < 0.05). We conclude that cerebral oxygen delivery was maintained by increased arterial inflow and this preceded the development of cerebral edema. Venous outflow restriction appeared to play a contributory role in the formation of cerebral edema, a novel feature that has not been observed previously.

Effect of fibre orientation on diastolic mechanics of human ventricle.

Fibre orientation of myocardial wall plays a significant role in ventricular wall stress, which is assumed to be responsible for many cardiac mechanics, including ventricular remodelling, associated with heart failure. Previous studies, conducted to identify the effects of fibre orientation on left -ventricle (LV) diastolic mechanics, used only animals myocardium properties (no human data) and therefore, may not apply for predicting human cardiac mechanics. In the present study, computational modelling of LV diastole was carried out to investigate the effects of fibre orientation on LV end diastolic pressure volume relation (EDPVR) and wall stress distribution using subject-specific in vivo passive properties of human myocardium for two human hearts. Results indicated that LV inflation increased when fibres were aligned more towards LV longitudinal axis and the effect was more notable when the fibre angle was higher in endocardium than epicardium wall. Changes in fibre angle distribution considerably altered fibre stress distribution of LV wall and the changes were significant in anterior and lateral regions of equatorial and apical locations. Furthermore, the regions of high fibre stress from midwall to endocardium were gradually confined towards endocardium with the decrease in fibre angle. Such information will be useful for future studies/diagnoses of LV mechanics in normal and pathological conditions.

Experiences of using a commercial dose management system (GE DoseWatch) for CT examinations

OBJECTIVE To assess the use of a commercial dose management system (GE DoseWatch; GEMS, Milwaukee, WI) for CT dose management for six common CT examinations. METHODS Data were acquired over several months using GE DoseWatch for six common CT examinations on three CT scanners. The dose length product (DLP) was taken as the dose indicator. The data were analysed using four different filtering methods: study description, the National Interim Clinical Imaging Procedure code, protocol name and a more detailed filtering method (the reference data set). The filtering methods were compared using an analysis of variance and multiple comparison technique. The different scanners were compared using the reference data set. RESULTS It was found that integrating DoseWatch with the radiology information system provided improved results compared with using the study description. Filtering by study description was found to be a poor indicator of the mean dose for all three scanners and consistently overestimated (p < 0.05) the head and thorax-abdo-pelvis mean DLP values, despite the large sample sizes. Filtering by the National Interim Clinical Imaging Procedure code or protocol name produced mean DLPs which were not statistically different from the reference data. The scanner intercomparison showed some significant differences between the scanners, usually due to different tube current modulation settings. CONCLUSION The use of a commercial dose monitoring system provided fast and efficient filtering of substantial amounts of data. The filtering method affected the mean DLP value despite large sample sizes. ADVANCES IN KNOWLEDGE Dose management systems are relatively new in the UK, and this article shares knowledge on the use of one system.

Brown fat depots in adult humans remain static in their locations on PET/CT despite changes in seasonality

Active brown adipose tissue (BAT) in humans has been demonstrated through use of positron emission tomography with 2‐deoxy‐2‐(fluorine‐18) fluoro‐D‐glucose integrated with computed tomography (18F‐FDG PET/CT) scans. The aim of our study was to determine whether active human BAT depots shown on 18F‐FDG PET/CT scans remain static in their location over time. This was a retrospective study. Adult human subjects (n = 15) who had had 18F‐FDG PET/CT imaging (n = 38 scans in total) for clinical reasons were included on the basis of 18F‐FDG uptake patterns consistent with BAT activity. For each subject, 18F‐FDG BAT uptake pattern on serial 18F‐FDG PET/CT images was compared to an index 18F‐FDG PET/CT image with the largest demonstrable BAT volume. Object‐based colocalization was expressed as Manders correlation coefficient (where 1 = 100% overlap, 0 = no overlap). Distribution of 18F‐FDG BAT activity over time and across multiple 18F‐FDG BAT scans was equivalent in 60% (n = 9) of the subjects. The degree of consistency in the pattern of 18F‐FDG BAT uptake in each subject over time was greater than expected by chance in 87% (n = 13) of the subjects (pair‐wise agreement 75–100%, Fleiss’ κ 0.4–1). The degree of BAT colocalization on serial scans was greater than that expected by chance in 93% (n = 14) of the subjects (mean Manders coefficient 0.81 ± 0.21 [95% CI]). To our knowledge, our study provides the most conclusive evidence to date to support the notion that active BAT depots in humans (volumes and activities of which were measured through use of 18F‐FDG PET/CT scans) remain static in location over sustained periods.

Estimating spatial resolution of in vivo mr images using spatial modulation of magnetization

Spatial Modulation of Magnetization is shown to provide a means of estimating perceived spatial resolution directly in vivo. On the first magnetic resonance system tested, resolution in conventional spin echo images was found to be stability limited in the phase encoding direction and voxel limited (via the Nyquist sampling theorem) in the frequency encoding direction both in vitro and in vivo. As the voxel size approaches half the stripe separation, fringes of resolved and unresolved stripes are formed across the image. This phenomenon is explained and described mathematically. On a second magnetic resonance scanner, resolution in the phase encoding direction of fast spin echo images with centrically ordered phase encoding is shown to be voxel limited in substances with long T2, with poorer resolution in substances with short T2. Resolution in fast spin echo images with linearly ordered phase encoding was shown to be voxel limited in the phase encoding direction.

Identification of an optimal threshold for detecting human brown adipose tissue using receiver operating characteristic analysis of IDEAL MRI fat fraction maps

PURPOSE Lower fat fraction (FF) in brown adipose tissue (BAT) than white adipose tissue (WAT) has been exploited using Dixon-based Magnetic Resonance Imaging (MRI) to differentiate these tissues in rodents, human infants and adults. We aimed to determine whether an optimal FF threshold could be determined to differentiate between BAT and WAT in adult humans in vivo. METHODS Sixteen volunteers were recruited (9 females, 7 males; 44.2 ± 19.2 years) based on BAT uptake on 18F-FDG PET/CT. Axial 3-echo TSE IDEAL sequences were acquired (TR(ms)/TE(ms)/matrix/NEX/FoV(cm) = 440/10.7-11.1/512 × 512/3/30-40), of the neck/upper thorax on a 3T HDxt MRI scanner (GE Medical Systems, Milwaukee, USA), and FF maps generated from the resulting water- and fat-only images. BAT depots were delineated on PET/CT based on standardized uptake values (SUV) >2.5 g/ml, and transposed onto FF maps. WAT depots were defined manually within subcutaneous fat. Receiver operating characteristic (ROC) analyses were performed, and optimal thresholds for differentiating BAT and WAT determined for each subject using Youdens J statistic. RESULTS There was large variation in optimal FF thresholds to differentiate BAT and WAT between subjects (0.68-0.85), with great variation in sensitivity (0.26-0.84) and specificity (0.62-0.99). FF was excellent or good at separating BAT and WAT in four cases (area under the curve [AUC] 0.84-0.92), but poor in 10 (AUC 0.25-0.68). CONCLUSION Although this technique was effective at differentiating BAT and WAT in some cases, no universal cut-off could be identified to reliably differentiate BAT and WAT in vivo in adult humans on the basis of FF.

Improved Thyroid Hypoechogenicity Following Bariatric-Induced Weight Loss in Euthyroid Adults With Severe Obesity—a Pilot Study

Background: Obesity may affect both biochemical thyroid function tests; and thyroid morphology, as assessed using ultrasound scans (US). The aim of the present pilot study was to explore whether weight loss achieved by bariatric surgery alters thyroid US morphology including gray-scale measurements; and/or function in euthyroid adults with severe obesity. Methods: Euthyroid adults (>18 years) with body mass index (BMI) ≥40 kg/m2 and negative thyroid peroxidase antibodies were assessed at baseline (pre-surgery) and after achieving at least 5% weight loss of their baseline body weight following bariatric surgery. Anthropometric assessments, biochemical/hormonal measurements (TSH, free-T4, free-T3, reverse-T3, and leptin) and thyroid US with gray-scale histogram analysis were performed at the baseline and post-surgery follow-up. Results: Ten Caucasian, euthyroid patients (women/men: 8/2; age: 48.6 ± 3.1 years; BMI: 51.4 ± 1.8 kg/m2) successfully completed this study with significantly decreased body weight (>5% weight loss), waist circumference and serum leptin levels post-surgery (mean post-surgery follow-up duration: 16.5 ± 2.5 months). In parallel to the observed bariatric-induced weight loss, thyroid US echogenicity increased by 25% (p = 0.03), without significant changes in thyroid volume. No significant changes in thyroid function tests were detected. No significant correlations were observed between the increase in thyroid echogenicity and the decreases in anthropometric parameters and circulating leptin. Conclusion: Our results indicate that in euthyroid adults with severe obesity, marked weight loss achieved by bariatric surgery is associated with a parallel significant increase in the thyroid US echogenicity, suggesting that morphological changes of the thyroid in obesity are reversible with weight loss. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03048708

Co-localisation analysis of brown adipose deposits on serial 18F-FDG PET/CT scans implies fixed deposits

Purpose: Brown adipose tissue (BAT) is the primary effector organ for non-shivering thermogenesis (NST), which positron emission tomography/computed tomography (PET/CT) studies have shown to be far more prevalent in adult humans than was hitherto believed. Research into weight loss by NST modulation through BAT manipulation requires a reliable imaging biomarker. This study evaluates patterns of BAT uptake on serial PET/CT scans to determine the degree of coincidence over time and the accuracy of PET/CT as a reference standard.

PC.26 Feasibility of Magnetic Resonance Spectroscopy in Examining Thalamic Metabolite Concentrations in a Multi-Centre Study of Neonatal Encephalopathy

Background Proton magnetic resonance spectroscopy (MRS) has high prognostic value in hypoxic ischaemic encephalopathy (HIE), however its multi-centre application is limited by inconsistencies between scanners and protocols. N-acetylaspartate (NAA) is predominantly neuronal: cerebral NAA concentration may be a more reliable HIE-severity biomarker than lactate/NAA. Objective To quantify the inter-site and inter-subject variability of NAA concentration measurements. Design/Methods We recruited 5 healthy adult volunteers (aged 24–38, 2 male, 3 female) whom we scanned at 3 UK sites participating in a multi-centre neonatal-brain study (University Hospital, Coventry (UHC); Alder Hey Children’s Hospital, Liverpool (AH); University College Hospital, London (UCLH)). Thalamic NAA concentration was measured using the neonatal brain-water concentration reference protocol (15 × 15 × 15mm3 voxel; PRESS; water-suppressed TR/TE = 2s/288&60ms; TR/TE = 5s/60ms; non-water-suppressed TR = 10s, TE = 60/124/205/316/495/1000 ms). Spectra were post-processed in jMRUI and metabolites fitted with LCModel. Results One volunteer was unavailable for scanning at AH. The mean (SD) NAA concentrations across the remaining four subjects were 15.5(3.4)mmol/kg wet weight, 14.4(0.1) mmol/kg wet weight, and 15.2(0.1) mmol/kg wet weight at UHC, AH and UCLH respectively. This corresponds to a maximum inter-site group mean variation (range/mean) of 8%. The inter-subject variability of mean NAA concentration (SD/mean) was 10%. Conclusions The variation of thalamic NAA concentration between sites was 8% and the standard deviation across subjects was 10%, hence [NAA] may be suitable for multi-centre studies. Abstract PC.26 Figure