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.

A longitudinal study of patients with cirrhosis treated with L-ornithine L-aspartate, examined with magnetization transfer, diffusion-weighted imaging and magnetic resonance spectroscopy.

The presence of overt hepatic encephalopathy (HE) is associated with structural, metabolic and functional changes in the brain discernible by use of a variety of magnetic resonance (MR) techniques. The changes in patients with minimal HE are less well documented. Twenty-two patients with well-compensated cirrhosis, seven of whom had minimal HE, were examined with cerebral 3 Tesla MR techniques, including T1- and T2-weighted, magnetization transfer and diffusion-weighted imaging and proton magnetic resonance spectroscopy sequences. Studies were repeated after a 4-week course of oral L-ornithine L-aspartate (LOLA). Results were compared with data obtained from 22 aged-matched healthy controls. There was no difference in mean total brain volume between patients and controls at baseline. Mean cerebral magnetization transfer ratios were significantly reduced in the globus pallidus and thalamus in the patients with cirrhosis irrespective of neuropsychiatric status; the mean ratio was significantly reduced in the frontal white matter in patients with minimal HE compared with healthy controls but not when compared with their unimpaired counterparts. There were no significant differences in either the median apparent diffusion coefficients or the mean fractional anisotropy, calculated from the diffusion-weighted imaging, or in the mean basal ganglia metabolite ratios between patients and controls. Psychometric performance improved in 50 % of patients with minimal HE following LOLA, but no significant changes were observed in brain volumes, cerebral magnetization transfer ratios, the diffusion weighted imaging variables or the cerebral metabolite ratios. MR variables, as applied in this study, do not identify patients with minimal HE, nor do they reflect changes in psychometric performance following LOLA.

Changes in Liver Volume in Patients with Chronic Hepatitis C Undergoing Antiviral Therapy.

AIM: Liver volumetric analysis has not been used to detect hepatic remodelling during antiviral therapy before. We measured liver volume (LV) changes on volumetric magnetic resonance imaging during hepatitis C antiviral therapy. METHODS: 22 biopsy-staged patients (median [range] age 45(19-65) years; 9F, 13M) with chronic hepatitis C virus infection were studied. LV was measured at the beginning, end of treatment and 6 months post-treatment using 3D T1-weighted acquisition, normalised to patient weight. Liver outlines were drawn manually on 4 mm thick image slices and LV calculated. Inter-observer agreement was analysed. Patients were also assessed longitudinally using biochemical parameters and liver stiffness using Fibroscan™. RESULTS: Sustained viral response (SVR) was achieved in 13 patients with a mean baseline LV/kg of 0.022 (SD 0.004) L/kg. At the end of treatment, the mean LV/kg was 0.025 (SD 0.004, P = 0.024 cf baseline LV/kg) and 0.026 (SD 0.004, P = 0.008 cf baseline LV/kg) 6 months post-treatment (P = 0.030 cf baseline, P = 0.004). Body weight-corrected end of treatment LV change was significantly higher in patients with SVR compared to patients not attaining SVR (P = 0.050). End of treatment LV change was correlated to initial ALT (R (2) = 0.479, P = 0.037), but not APRI, AST, viral load or liver stiffness measurements. There was a correlation of 0.89 between observers for measured slice thickness. CONCLUSIONS: LV increased during anti-viral treatment, while the body weight-corrected LV increase persisted post-antiviral therapy and was larger in patients with SVR.

Quantitative magnetic resonance imaging in patients with cirrhosis: a cross-sectional study.

Cerebral magnetic resonance imaging was undertaken, at 3 Tesla field strength, employing magnetization transfer (MT) and diffusion-weighted imaging (DWI) sequences, in 26 patients with well-compensated cirrhosis, free of overt hepatic encephalopathy. Results were compared to those from 18 aged-matched healthy volunteers. Cerebral magnetization transfer ratios (MTR) were reduced in the frontal white matter, caudate, putamen and globus pallidus in patients with cirrhosis, compared to healthy controls, while the apparent diffusion coefficients (ADC) on DWI were significantly increased in the genu and body of the corpus callosum. An association between previous excessive alcohol consumption and both MTR and ADCs was noted, but this association was lost when controls were exercised for the severity of liver disease and psychometric impairment on multivariate analysis. Eight (31 %) of the 26 patients had impaired psychometric performance consistent with a diagnosis of minimal hepatic encephalopathy. No statistically significant difference in regional cerebral MTRs or ADCs was found in relation to neuropsychiatric status, although there was a trend towards lower MTRs in patients with impaired psychometric performance. The alterations in MTR and ADC in the patients with functionally compensated cirrhosis are compatible with theories governing the genesis of hepatic encephalopathy, including changes in astrocyte membrane permeability, with subsequent redistribution of macromolecules.

The impact of oligofructose on stimulation of gut hormones, appetite regulation and adiposity.

OBJECTIVE: To investigate the effect of nutrient stimulation of gut hormones by oligofructose supplementation on appetite, energy intake (EI), body weight (BW) and adiposity in overweight and obese volunteers. METHODS: In a parallel, single-blind and placebo-controlled study, 22 healthy overweight and obese volunteers were randomly allocated to receive 30 g day(-1) oligofructose or cellulose for 6 weeks following a 2-week run-in. Subjective appetite and side effect scores, breath hydrogen, serum short chain fatty acids (SCFAs), plasma gut hormones, glucose and insulin concentrations, EI, BW and adiposity were quantified at baseline and post-supplementation. RESULTS: Oligofructose increased breath hydrogen (P < 0.0001), late acetate concentrations (P = 0.024), tended to increase total area under the curve (tAUC)420 mins peptide YY (PYY) (P = 0.056) and reduced tAUC450 mins hunger (P = 0.034) and motivation to eat (P = 0.013) when compared with cellulose. However, there was no significant difference between the groups in other parameters although within group analyses showed an increase in glucagon-like peptide 1 (GLP-1) (P = 0.006) in the cellulose group and a decrease in EI during ad libitum meal in both groups. CONCLUSIONS: Oligofructose increased plasma PYY concentrations and suppressed appetite, while cellulose increased GLP-1 concentrations. EI decreased in both groups. However, these positive effects did not translate into changes in BW or adiposity.

Modulation of neural activation following treatment of hepatic encephalopathy.

OBJECTIVE: To measure changes in psychometric state, neural activation, brain volume (BV), and cerebral metabolite concentrations during treatment of minimal hepatic encephalopathy. METHODS: As proof of principle, 22 patients with well-compensated, biopsy-proven cirrhosis of differing etiology and previous minimal hepatic encephalopathy were treated with oral l-ornithine l-aspartate for 4 weeks. Baseline and 4-week clinical review, blood chemistry, and psychometric evaluation (Psychometric Hepatic Encephalopathy Score and Cognitive Drug Research Score) were performed. Whole-brain volumetric and functional MRI was conducted using a highly simplistic visuomotor task, together with proton magnetic resonance spectroscopy of the basal ganglia. Treatment-related changes in regional BV and neural activation change (blood oxygenation level dependent) were assessed. RESULTS: Although there was no change in clinical, biochemical state, basal ganglia magnetic resonance spectroscopy, or in regional BV, there were significant improvements in Cognitive Drug Research Score (+1.2, p = 0.003) and Psychometric Hepatic Encephalopathy Score (+1.5, p = 0.003) with treatment. This cognitive amelioration was accompanied by changes in blood oxygenation level-dependent activation in the posterior cingulate and ventral medial prefrontal cortex, 2 regions that form part of the brain's structural and metabolic core. In addition, there was evidence of greater visual cortex activation. CONCLUSIONS: These structurally interconnected regions all showed increased function after successful encephalopathy treatment. Because no regional change in BV was observed, this implies that mechanisms unrelated to astrocyte volume regulation were involved in the significant improvement in cognitive performance.

Accuracy and reliability of microbubble ultrasound measurements for the non-invasive assessment of hepatic fibrosis in chronic hepatitis C.

AIM: Contrast-enhanced ultrasound can be used to assess liver disease severity non-invasively by observing intra- and extrahepatic hemodynamic changes. Transit times are calculated to include intra- and extrahepatic components (hepatic vein transit time, HVTT) or the intrahepatic component (hepatic transit time, HTT), but these have not been compared directly. We aimed to compare diagnostic accuracy of HVTT and HTT in gauging the severity of chronic hepatitis C (CHC) and to assess inter- and intra-observer reliability. METHODS: Recorded ultrasound scans performed on 75 patients with biopsy-staged CHC, using the microbubble contrast agent Sonovue were analyzed. RESULTS: Diagnostic accuracy of HTT and HVTT for diagnosis of cirrhosis was 0.78 and 0.71 (P = 0.24). Diagnostic accuracy of HTT and HVTT for diagnosis of fibrosis stage >2 was 0.76 and 0.72 (P = 0.23). Negative predictive value for cirrhosis using this cut-off was high for both techniques (HVTT, 88%; HTT, 92%), suggesting utility for exclusion of cirrhosis. Inter-observer reliability for HTT and HVTT were 0.92 and 0.94, respectively. Intra-observer reliability for HTT and HVTT were 0.98 and 0.99. CONCLUSION: In this cohort, reliability exceeded 90% while diagnostic accuracy was in keeping with previous studies of microbubble transit time analysis. Despite higher numerical diagnostic accuracy for HTT, no significant difference was demonstrated between the techniques, suggesting that both methods can be used reliably.

The missing risk: MRI and MRS phenotyping of abdominal adiposity and ectopic fat.

Individual compartments of abdominal adiposity and lipid content within the liver and muscle are differentially associated with metabolic risk factors, obesity and insulin resistance. Subjects with greater intra-abdominal adipose tissue (IAAT) and hepatic fat than predicted by clinical indices of obesity may be at increased risk of metabolic diseases despite their "normal" size. There is a need for accurate quantification of these potentially hazardous depots and identification of novel subphenotypes that recognize individuals at potentially increased metabolic risk. We aimed to calculate a reference range for total and regional adipose tissue (AT) as well as ectopic fat in liver and muscle in healthy subjects. We studied the relationship between age, body-mass, BMI, waist circumference (WC), and the distribution of AT, using whole-body magnetic resonance imaging (MRI), in 477 white volunteers (243 male, 234 female). Furthermore, we used proton magnetic resonance spectroscopy (MRS) to determine intrahepatocellular (IHCL) and intramyocellular (IMCL) lipid content. The anthropometric variable which provided the strongest individual correlation for adiposity and ectopic fat stores was WC in men and BMI in women. In addition, we reveal a large variation in IAAT, abdominal subcutaneous AT (ASAT), and IHCL depots not fully predicted by clinically obtained measurements of obesity and the emergence of a previously unidentified subphenotype. Here, we demonstrate gender- and age-specific patterns of regional adiposity in a large UK-based cohort and identify anthropometric variables that best predict individual adiposity and ectopic fat stores. From these data we propose the thin-on-the-outside fat-on-the-inside (TOFI) as a subphenotype for individuals at increased metabolic risk.

Recent advances in imaging hepatic fibrosis and steatosis.

Liver disease is an increasing cause of morbidity and mortality worldwide. Currently, the gold standard for diagnosis and assessment of parenchymal disease is histopathological assessment of a percutaneous or transjugular liver biopsy. The risks and limitations of this technique are well recognized and as a result, significant effort has gone into the development of novel noninvasive methods of diagnosis and longitudinal assessment. Imaging techniques have improved significantly over the past decade and new technologies are beginning to enter clinical practice. Ultrasound, computed tomography and MRI are the main modalities currently used, but novel MRI-based techniques will have an increasing role. While there has been extensive research into the imaging of focal liver disease, the evidence base for imaging in diffuse disease has also undergone recent rapid development, particularly in the assessment of fibrosis and steatosis. Both of these abnormalities of the parenchyma can lead to cirrhosis and/or hepatocellular carcinoma and represent an important opportunity for detection of early liver disease. We discuss the recent advances in liver imaging techniques and their role in the diagnosis and monitoring of diffuse liver disease, with a focus on their current and potential clinical relevance and whether they may replace or augment liver biopsy. We also discuss techniques currently under development and their potential clinical applications in the future.

Functional cardiac MRI in preterm and term newborns.

OBJECTIVE: To use cardiac MRI techniques to assess ventricular function and systemic perfusion in preterm and term newborns, to compare techniques to echocardiographic methods, and to obtain initial reference data. DESIGN: Observational magnetic resonance and echocardiographic imaging study. SETTING: Neonatal Unit, Queen Charlotte's and Chelsea Hospital, London, UK. Patients 108 newborn infants with median birth weight 1627 (580-4140) g, gestation 32 (25-42) weeks. RESULTS: Mean (SD) flow volumes assessed by phase contrast (PC) imaging in 28 stable infants were left ventricular output (LVO) 222 (46), right ventricular output (RVO) 219 (47), superior vena cava (SVC) 95 (27) and descending aorta (DAo) 126 (32) ml/kg/min, with flow being higher at lower gestational age. Limits of agreement for repeated PC assessment of flow were LVO ±50.2, RVO ±55.5, SVC ±20.9 and DAo ±26.2 ml/kg/min. Mean (SD) LVO in 75 stable infants from three-dimensional models were 245 (47) ml/kg/min, with limits of agreement ±58.3 ml/kg/min. Limits of agreement for repeated echocardiographic assessment of LVO were ±108.9 ml/kg/min. CONCLUSIONS: Detailed magnetic resonance assessments of cardiac function and systemic perfusion are feasible in newborn infants, and provide more complete data with greater reproducibility than existing echocardiographic methods. Functional cardiac MRI could prove to be a useful research technique to study small numbers of newborn infants in specialist centres; providing insights into the pathophysiology of circulatory failure; acting as an outcome measure in clinical trials of inotropic intervention and so guiding clinical practice in the wider neonatal community.

Three-tesla cardiac magnetic resonance imaging for preterm infants.

OBJECTIVES: We aimed to establish the feasibility of acquiring 3.0-T cardiac MRIs without sedation, anesthesia, or breath-holding for preterm infants and to obtain preliminary quantitative data on left ventricular function in this population. METHODS: Twelve preterm infants underwent 3.0-T cardiac MRI without sedation or breath-holding. The median gestational age was 29 weeks (range: 26-33 weeks), the median birth weight was 1240 g (range: 808-2200 g), and the median postconceptional age at the time of cardiac MRI was 33 weeks (range: 31-40 weeks). Anatomic images were acquired with T2-weighted spin-echo sequences, and ventricular function was assessed with balanced steady-state free precession cine sequences. We assessed left ventricular function by using the area-length ejection fraction method on horizontal long-axis images and the volumetric Sergeant's discs method of analysis on short-axis images. RESULTS: Imaging was successful for 10 of 12 infants. For those 10, the area-length ejection fraction method in the horizontal long-axis plane estimated median stroke volume at 2.9 mL, cardiac output at 0.4 L/minute, end-diastolic volume at 3.8 mL, end-systolic volume at 0.3 mL, and ejection fraction at 74.6%. Short-axis volumetric estimations were made for 4 infants. With this approach, the median stroke volume was 2.4 mL, cardiac output 0.35 L/minute, end-diastolic volume 4.3 mL, end-systolic volume 2.1 mL, and ejection fraction 56%. CONCLUSIONS: Three-tesla cardiac MRI is feasible for preterm infants without sedation, anesthesia, or breath-holding and has the potential to provide a wide range of precise quantitative data that may be of great value for the investigation of cardiac function in preterm infants.

The effect of preterm birth on neonatal cerebral vasculature studied with magnetic resonance angiography at 3 Tesla.

Preterm birth is associated with a high incidence of neurodevelopmental deficits. Magnetic resonance imaging (MRI) has proved to be a valuable tool for monitoring development in the preterm brain. We used a dedicated time-of-flight (TOF) magnetic resonance angiography (MRA) protocol at 3 Tesla (3T) optimized to assess morphological characteristics of the neonatal cerebral vessels associated with preterm birth in a sample of 37 infants. We found statistically significant decreased tortuosity in all proximal segments of the cerebral vasculature (anterior, middle and posterior cerebral arteries) in the preterm infants imaged at term equivalent age compared to the term born infants, with no differences in vessel diameter between the two groups. This distinct phenotype of decreased tortuosity was shown to persist until 18 months of age in longitudinal MRA studies in infants born preterm, suggesting that this is not a delay in maturation. Biparietal head diameter measurements were significantly smaller in the preterm at term infants and were inversely correlated with middle cerebral artery tortuosity measurements in both the term born and the preterm at term infants. To our knowledge, this is the first systematic MRA study on the effect of preterm delivery on neonatal cerebral vasculature. Our intention is to build on the findings of this study by combining the data with other measurements of brain growth and vascular haemodynamics to understand more about the interdependence of vessel and brain development and their relationship to prematurity.