Changes in lumbar muscle diffusion tensor indices with age.

Objective: To investigate differences in diffusion tensor imaging (DTI) parameters and proton density fat fraction (PDFF) in the spinal muscles of younger and older adult males. Methods: Twelve younger (19-30 years) and 12 older (61-81years) healthy, physically active male participants underwent T1W, T2W, Dixon and DTI of the lumbar spine. The eigenvalues (λ1, λ2, and λ3), fractional anisotropy (FA), and mean diffusivity (MD) from the DTI together with the PDFF were determined in the multifidus, medial and lateral erector spinae (ESmed, ESlat), and quadratus lumborum (QL) muscles. A two-way ANOVA was used to investigate differences with age and muscle and t-tests for differences in individual muscles with age. Results: The ANOVA gave significant differences with age for all DTI parameters and the PDFF (P < .01) and with muscle (P < .01) for all DTI parameters except for λ1 and for the PDFF. The mean of the eigenvalues and MD were lower and the FA higher in the older age group with differences reaching statistical significance for all DTI measures for ESlat and QL (P < .01) but only in ESmed for λ3 and MD (P < .05). Conclusions: Differences in DTI parameters of muscle with age result from changes in both in the intra- and extra-cellular space and cannot be uniquely explained in terms of fibre length and diameter. Advances in knowledge: Previous studies looking at age have used small groups with uneven age spacing. Our study uses two well defined and separated age groups.

More than skin-deep: visceral fat is strongly associated with disease activity, function and metabolic indices in psoriatic disease.

OBJECTIVE: To compare body composition between patients with psoriatic disease (PsD), including cutaneous psoriasis (PsO) and psoriatic arthritis (PsA), and controls, and to explore associations between disease activity and measures of function and metabolic derangement. METHODS: Body composition was assessed by air displacement plethysmography (ADP) and MRI-derived fat segmentation using an automated pipeline (FatSegNet). Function was assessed by Health Assessment Questionnaire (HAQ) and metabolic status by fasting lipid profile, insulin and adiponectin. Active and inactive PsO and PsA were defined by body surface area (BSA) and Psoriasis Area Severity Index (PASI) and minimal disease activity (MDA), respectively. RESULTS: Thirty patients (median disease duration 15 years; median age 52 years) and 30 BMI-matched controls were enrolled. Compared with controls, all MRI-derived body composition parameters-whole-body volume, subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), abdominal adipose tissue (AAT), VAT/AAT and VAT/SAT-were higher in the PsD group, specifically, those with active disease. Body mass, body fat, whole-body volume and whole-body VAT were correlated with higher triglycerides, cholesterol:HDL (high-density lipoprotein), insulin resistance and lower adiponectin as well as higher HAQ and lower MDA. CONCLUSIONS: In this pilot study, patients with PsD revealed excessive total adipose tissue and a greater volume of metabolically unfavourable ectopic fat, including VAT, compared with BMI-matched controls, which also correlated with HAQ, disease activity and overall dysmetabolism. We also provide the first evidence in patients with PsD for the clinical application of FatSegNet: a novel, automated and rapid deep learning pipeline for providing accurate MRI-based measurement of fat segmentation. Our findings suggest the need for a more integrated approach to the management of PsD, which considers both the metabolic and inflammatory burden of disease. More specifically, visceral fat is a surrogate marker of uncontrolled PsD and may be an important future target for both pharmacological and lifestyle interventions.

Quantification and correction of distortion in diffusion-weighted MRI at 1.5 and 3 T in a muscle-invasive bladder cancer phantom for radiotherapy planning.

OBJECTIVE: Limited visibility of post-resection muscle-invasive bladder cancer (MIBC) on CT hinders radiotherapy dose escalation of the residual tumour. Diffusion-weighted MRI (DW-MRI) visualises areas of high tumour burden and is increasingly used within diagnosis and as a biomarker for cancer. DW-MRI could, therefore, facilitate dose escalation, potentially via dose-painting and/or accommodating response. However, the distortion inherent in DW-MRI could limit geometric accuracy. Therefore, this study aims to quantify DW-MRI distortion via imaging of a bladder phantom. METHODS: A phantom was designed to mimic MIBC and imaged using CT, DW-MRI and T2W-MRI. Fiducial marker locations were compared across modalities and publicly available software was assessed for correction of magnetic susceptibility-related distortion. RESULTS: Fiducial marker locations on CT and T2W-MRI agreed within 1.2 mm at 3 T and 1.8 mm at 1.5 T. The greatest discrepancy between CT and apparent diffusion coefficient (ADC) maps was 6.3 mm at 3 T, reducing to 1.8 mm when corrected for distortion. At 1.5 T, these values were 3.9 mm and 1.7 mm, respectively. CONCLUSIONS: Geometric distortion in DW-MRI of a model bladder was initially >6 mm at 3 T and >3 mm at 1.5 T; however, established correction methods reduced this to <2 mm in both cases. ADVANCES IN KNOWLEDGE: A phantom designed to mimic MIBC has been produced and used to show distortion in DW-MRI can be sufficiently mitigated for incorporation into the radiotherapy pathway. Further investigation is therefore warranted to enable individually adaptive image-guided radiotherapy of MIBC based upon DW-MRI.

Age-related degeneration of lumbar muscle morphology in healthy younger versus older men.

AIM: The aim of this study was to evaluate age-related changes in lumbar paravertebral muscle (LPM) morphology in healthy younger and older adult men. METHODS: T2-weighted axial MRI of the lumbar spine were obtained for 12 healthy older (67.3 ± 6.0 years) and younger (24.7 ± 3.1 years) men. Normalised muscle volume (NMV) and muscle fat infiltrate (MFI) were determined bilaterally for the psoas (PS), quadratus lumborum (QL), erector spinae (ES) and multifidus (MF). MANOVA was used to compare NMV and MFI between age groups. Follow-up ANOVA compared NMV and MFI for each muscle between age groups, with physical activity (PA) as a covariate. Stepwise regression was used to explore the association between muscle morphology. RESULTS: NMV of the ES and QL were significantly lower in the older group (OG) (p = 0.040 and p < 0.001, respectively). MFI across all muscles was significantly greater in the OG (p < 0.001). PA did not moderate the relationship between aging and muscle degeneration. Non-dominant handgrip strength was associated with NMV (p = 0.003). CONCLUSIONS: Age-related atrophy is muscle specific in the lumbar spine; changes in lumbar musculature is independent of PA, handgrip strength may reflect morphological changes in the postural muscles with age. This study supports establishing effective targeted exercise interventions in the lumbar musculature.

An investigation into the effect of body mass index on the agreement between whole-body fat mass determined by MRI and air-displacement plethysmography.

OBJECTIVE: To validate MRI fat measurement protocols using purpose built test objects and by comparison with air-displacement plethysmography (ADP) whole-body fat measurements in non-obese subjects. METHODS: Test objects of known fat concentration were used to quantify the accuracy of the MRI measurements. 10 participants with a body mass index in the range 18-30 underwent whole-body MRI using two different Dixon-based sequences (LAVA Flex and IDEAL IQ) to obtain an estimate of their whole-body fat mass. The MRI determined fat mass was compared to the fat mass determined by ADP. RESULTS: MRI test object measurements showed a high correlation to expected fat percentage (r > 0.98). The participant MRI and ADP results were highly correlated (r = 0.99) but on average (mean ± standard deviation) MRI determined a higher fat mass than ADP (3.8 ± 3.1 kg for LAVA Flex and 1.9 ± 3.2 kg for IDEAL IQ). There was no trend in the difference between MRI and ADP with total fat mass. CONCLUSION: The good agreement between MRI and ADP shows that Dixon-based MRI can be used effectively as a tool in physiological research for non-obese adults. ADVANCES IN KNOWLEDGE: This work found that for ten non-obese subjects body mass index had no effect on the MRI determination of whole-body fat mass.

Magnetic resonance spectroscopy assessment of brain injury after moderate hypothermia in neonatal encephalopathy: a prospective multicentre cohort study.

BACKGROUND: In neonatal encephalopathy, the clinical manifestations of injury can only be reliably assessed several years after an intervention, complicating early prognostication and rendering trials of promising neuroprotectants slow and expensive. We aimed to determine the accuracy of thalamic proton magnetic resonance (MR) spectroscopy (MRS) biomarkers as early predictors of the neurodevelopmental abnormalities observed years after neonatal encephalopathy. METHODS: We did a prospective multicentre cohort study across eight neonatal intensive care units in the UK and USA, recruiting term and near-term neonates who received therapeutic hypothermia for neonatal encephalopathy. We excluded infants with life-threatening congenital malformations, syndromic disorders, neurometabolic diseases, or any alternative diagnoses for encephalopathy that were apparent within 6 h of birth. We obtained T1-weighted, T2-weighted, and diffusion-weighted MRI and thalamic proton MRS 4-14 days after birth. Clinical neurodevelopmental tests were done 18-24 months later. The primary outcome was the association between MR biomarkers and an adverse neurodevelopmental outcome, defined as death or moderate or severe disability, measured using a multivariable prognostic model. We used receiver operating characteristic (ROC) curves to examine the prognostic accuracy of the individual biomarkers. This trial is registered with ClinicalTrials.gov, number NCT01309711. FINDINGS: Between Jan 29, 2013, and June 25, 2016, we recruited 223 infants who all underwent MRI and MRS at a median age of 7 days (IQR 5-10), with 190 (85%) followed up for neurological examination at a median age of 23 months (20-25). Of those followed up, 31 (16%) had moderate or severe disability, including one death. Multiple logistic regression analysis could not be done because thalamic N-acetylaspartate (NAA) concentration alone accurately predicted an adverse neurodevelopmental outcome (area under the curve [AUC] of 0·99 [95% CI 0·94-1·00]; sensitivity 100% [74-100]; specificity 97% [90-100]; n=82); the models would not converge when any additional variable was examined. The AUC (95% CI) of clinical examination at 6 h (n=190) and at discharge (n=167) were 0·72 (0·65-0·78) and 0·60 (0·53-0·68), respectively, and the AUC of abnormal amplitude integrated EEG at 6 h (n=169) was 0·73 (0·65-0·79). On conventional MRI (n=190), cortical injury had an AUC of 0·67 (0·60-0·73), basal ganglia or thalamic injury had an AUC of 0·81 (0·75-0·87), and abnormal signal in the posterior limb of internal capsule (PLIC) had an AUC of 0·82 (0·76-0·87). Fractional anisotropy of PLIC (n=65) had an AUC of 0·82 (0·76-0·87). MRS metabolite peak-area ratios (n=160) of NAA-creatine (<1·29) had an AUC of 0·79 (0·72-0·85), of NAA-choline had an AUC of 0·74 (0·66-0·80), and of lactate-NAA (>0·22) had an AUC of 0·94 (0·89-0·97). INTERPRETATION: Thalamic proton MRS measures acquired soon after birth in neonatal encephalopathy had the highest accuracy to predict neurdevelopment 2 years later. These methods could be applied to increase the power of neuroprotection trials while reducing their duration. FUNDING: National Institute for Health Research UK.

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.

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 ±â€¯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 Youden's 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.

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 Mander's 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 Mander's 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.

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.

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.

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 animal's 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.

Quality control within the multicentre perfusion CT study of primary colorectal cancer (PROSPeCT): results of an iodine density phantom study.

OBJECTIVES: To assess the cross-centre consistency of iodine enhancement, contrast-to-noise ratio and radiation dose in a multicentre perfusion CT trial of colorectal cancer. MATERIALS AND METHODS: A cylindrical water phantom containing different iodine inserts was examined on seven CT models in 13 hospitals. The relationship between CT number (Hounsfield units, HU) and iodine concentration (milligrams per millilitre) was established and contrast-to-noise ratios (CNRs) calculated. Radiation doses (CTDIvol, DLP) were compared across all sites. RESULTS: There was a linear relationship between CT number and iodine density. Iodine enhancement varied by a factor of at most 1.10, and image noise by at most 1.5 across the study sites. At an iodine concentration of 1 mg ml(-1) and 100 kV, CNRs ranged from 3.6 to 4.8 in the 220-mm phantom and from 1.4 to 1.9 in the 300-mm phantom. Doses varied by a factor of at most 2.4, but remained within study dose constraints. Iterative reconstruction algorithms did not alter iodine enhancement but resulted in reduced image noise by a factor of at most 2.2, allowing a potential dose decrease of at most 80% compared to filtered back projection (FBP). CONCLUSIONS: Quality control of CT performance across centres indicates that CNR values remain relatively consistent across all sites, giving acceptable image quality within the agreed dose constraints. KEY POINTS: Quality control is essential in a multicentre setting to enable CT quantification. CNRs in a body-sized phantom had the recommended value of at least 1.5. CTDIs and DLPs varied by factors of 1.8 and 2.4 respectively.

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.

Sleep problems in children with cerebral palsy and their relationship with maternal sleep and depression.

AIM: To compare sleep problems in children with cerebral palsy to typically developing children. To study the relationship between sleep problems in children with cerebral palsy and maternal sleep quality and depression. METHODS: Fifty-seven children with cerebral palsy aged 4-12 years were identified from a UK disability database. Maternal sleep disturbance and mood were assessed using the Pittsburgh Sleep Quality Index and the Major Depression Inventory. Child sleep problems, assessed with the Children's Sleep Habits Questionnaire, but not maternal variables, were compared to 102 typically developing children. RESULTS: Forty children (70%) were recruited with a mean age of 7.8 (SD 2.4). Sleep anxiety, night wakings, parasomnias and sleep-disordered breathing sub-scales indicated significantly more difficulties than in typically developing children. 40% of mothers of children with cerebral palsy had poor sleep quality of whom 44% had depressed mood. Child and maternal sleep disturbance were significantly correlated. Maternal sleep quality predicted 50% of the variance in maternal depression. CONCLUSIONS: Children with cerebral palsy have more sleep problems than typically developing peers. Their mothers also have disturbed sleep that correlates with maternal depression. Childhood sleep problems can be treated and should be identified in routine clinical practice.