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Biomedical subjects

Gavin Hamilton

Publications and source records attributed to Gavin Hamilton.

12 recordsLinked to original sources

Effect of nutritional counselling on hepatic, muscle and adipose tissue fat content and distribution in non-alcoholic fatty liver disease.

AIM: To assess the effectiveness of the current UK clinical practice in reducing hepatic fat (IHCL). METHODS: Whole body MRI and (1)H MRS were obtained, before and after 6 mo nutritional counselling, from liver, soleus and tibialis muscles in 10 subjects with non-alcoholic fatty liver disease (NAFLD). RESULTS: A 500 Kcal-restricted diet resulted in an average weight loss of 4% (-3.4 kg,) accompanied by significant reductions in most adipose tissue (AT) depots, including subcutaneous (-9.9%), abdominal subcutaneous (-10.2%) and intra-abdominal-AT (-11.4%). Intramyocellular lipids (IMCL) were significantly reduced in the tibialis muscle (-28.2%). Decreases in both IHCL (-39.9%) and soleus IMCL (-12.2%) content were also observed, although these were not significant. Several individuals showed dramatic decreases in IHCL, while others paradoxically showed increases in IHCL content. Changes in body composition were accompanied by improvements in certain liver function tests: serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Significant correlations were found between decreases in IHCL and reductions in both intra-abdominal and abdominal subcutaneous AT. Improvements in liver function tests were associated with reductions in intra-abdominal AT, but not with changes in IHCL. CONCLUSION: This study shows that even a very modest reduction in body weight achieved through lifestyle modification can result in changes in body fat depots and improvements in LFTs.

Adipose Tissue, White↗

Variations due to analysis technique in intracellular pH measurements in simulated and in vivo 31P MR spectra of the human brain.

PURPOSE: To investigate variation in pH generated by different analysis techniques and to find the most robust method, 31P MR brain spectra were acquired in vivo. Three different methods were used to measure the chemical shift of inorganic phosphate (Pi) relative to phosphocreatine (PCr). MATERIALS AND METHODS: Eight healthy volunteers were scanned four times, and manual measurement of the chemical shift in a frequency domain spectrum using the manufacturer's software was compared with values produced by a frequency-domain analysis method (NMR1) and a prior-knowledge-based time-domain technique (MRUI). To explain the in vivo data, simulations of brain spectra, modified in ways typical of real variations in vivo, were produced and the pH was measured using manual measurement and MRUI. RESULTS: Different measurement techniques produced systematically different pH values, with manual measurement producing the lowest variability (manual measurement: pH = 6.999, CoV = 0.297; NMR1: pH = 7.042, CoV = 0.501; MRUI: pH = 7.036, CoV = 0.606). While MRUI more accurately measured the pH of unaltered simulations, it was systematically affected by altering the simulated spectra. Manual measurement was unaffected. CONCLUSION: Manual measurement produces the most consistent pH value, and there is no benefit in using more complex automated spectral fitting methods to measure the pH.

Adult↗

Excess visceral and hepatic adipose tissue in Turner syndrome determined by magnetic resonance imaging: estrogen deficiency associated with hepatic adipose content.

Obesity, predominantly centrally distributed, is common in women with Turner syndrome (TS) and is thought to contribute to the increased risk of atherosclerosis; however, insulin concentrations are unexpectedly low. To explore this discrepancy, we assessed fat content and distribution by magnetic resonance imaging (MRI) and bioelectrical impedance (BI). Six nondiabetic, estrogen-treated women with TS were compared with six age-matched normal controls of similar body mass index. Clinical history, anthropometric measurements, biochemical markers, and MRI and BI measures of adiposity were assessed. TS women had increased intrahepatocellular lipids (IHCL) on MRI. After height adjustment, they also had an excess of total and visceral compared with sc adipose tissue (AT) than controls, without elevated insulin concentrations. BI and MRI measures correlated strongly for total and sc, but not visceral, AT in TS. IHCL was associated with cumulative estrogen-deficient years (r = 0.928; P = 0.008). Women with TS depart from the classical picture of metabolic syndrome despite an excess of total and visceral AT on MRI. Elevated IHCL in TS is associated with estrogen deficiency. BI may be useful to estimate total body fat, but does not reliably localize fat depots in TS.

Adipose Tissue↗

A review of cognitive impairment and cerebral metabolite abnormalities in patients with hepatitis C infection.

Numerous studies have reported associations between chronic hepatitis C virus (HCV) infection and fatigue, depression and impairments in health-related quality of life, which are independent of the severity of liver disease. Although there are a large number of potential explanations for these symptoms, including a history of substance abuse and associated personality types, or the effect of the diagnosis of HCV infection itself, there has been recent interest in the possibility of a biological effect of HCV infection on cerebral function. There is emerging evidence of mild, but significant neurocognitive impairment in HCV infection, which cannot be wholly attributed to substance abuse, co-existent depression or hepatic encephalopathy. Impairments are predominantly in the domains of attention, concentration and information processing speed. Furthermore, in-vivo cerebral magnetic resonance spectroscopy studies in patients with hepatitis C and normal liver function have reported elevations in cerebral choline-containing compounds and reductions in N-acetyl aspartate, suggesting that a biological mechanism may underlie the cognitive findings. The recent detection of HCV genetic sequences in post-mortem brain tissue raises the intriguing possibility that HCV infection of the central nervous system may be related to the reported neuropsychological symptoms and cognitive impairment.

Brain↗

In vivo and in vitro nuclear magnetic resonance spectroscopy as a tool for investigating hepatobiliary disease: a review of H and P MRS applications.

Nuclear magnetic resonance (NMR) spectroscopy is a non-invasive technique, which allows the study of cellular biochemistry and metabolism. It is a diverse research tool, widely used by biochemists to investigate pathophysiological processes in vitro and, more recently, by physicians to determine disease abnormalities in vivo. This article reviews the basics of the NMR phenomenon and summarises previous research on the hepatobiliary system using both laboratory-based and clinical methodologies. The role of proton and phosphorus-31 ((31)P) NMR spectroscopy in the study of malignant and non-malignant liver disease and studies of bile composition are discussed. In vivo techniques (magnetic resonance spectroscopy, MRS) can be performed as an adjunct to standard MR examination of the liver. Although still primarily a research tool, the in vivo technique provides non-invasive biochemical information on disease severity and holds promise in its use to gauge response to treatment regimens.

Biliary Tract Diseases↗

Phosphorus-31 brain MR spectroscopy in women during and after pregnancy compared with nonpregnant control subjects.

BACKGROUND AND PURPOSE: A reversible decrease in brain size has been demonstrated during normal pregnancy that is maximal at term and returns to normal after many months. The purpose of this longitudinal study was to use phosphorus-31 MR spectroscopy to determine if metabolic changes explain this physiologic event. METHODS: Pregnant women (n = 12) were examined at term and up to 6 months after delivery. Nonpregnant control subjects (n = 7) were imaged twice (a month apart) to exclude hormone effects. Brain (31)P MR spectra were acquired at 1.5 T, and intracellular pH was calculated from the chemical shift between phosphocreatine and inorganic phosphate resonances. Statistical analysis was performed by using an analysis of variance. RESULTS: We found no statistically significant differences in the relative levels of metabolite associated with cerebral bioenergetics and cell membrane metabolism between pregnant women and nonpregnant women. However, a significant increase in cerebral pH was observed in pregnant women at 6 weeks after delivery compared with control subjects (7.074 +/- 0.063 vs 7.017 +/- 0.041; P < .05). pH returned to normal by 6 months after delivery (7.014 +/- 0.010). CONCLUSION: Changes in brain size associated with pregnancy appear to be associated with an increase in intracellular pH after delivery. The observed alkalosis may reflect altered cellular metabolism. These persistent brain perturbations associated with pregnancy indicate that, when postpartum physiologic and pharmacologic changes are measured, long-term effects may be expected in central nervous system processing.

Adult↗

Altered adiposity after extremely preterm birth.

The quantity and distribution of adipose tissue are markers of morbidity risk. The third trimester of human development is a period of rapid adipose tissue deposition. Preterm infants may be at risk of altered adiposity. We measured anthropometric indices and quantified total, subcutaneous, and intraabdominal adipose tissue volumes using whole-body magnetic resonance adipose tissue imaging in 38 infants born at <32 wk gestational age, when they reached term, and 29 term-born infants. The preterm infants at term were significantly lighter and shorter than the term-born infants, but there was no significant difference in head circumference SD score or total adiposity. The preterm infants had a highly significant decrease in subcutaneous adipose tissue and significantly increased intraabdominal adipose tissue. Accelerated postnatal weight gain was accompanied by increased total and subcutaneous adiposity. Illness severity was the principal determinant of increased intraabdominal adiposity. Our data provide evidence of causal pathways linking accelerated postnatal growth with increased total and subcutaneous adiposity, and illness severity with altered adipose tissue partitioning. We suggest that these observations may in part explain the associations between small size at birth and later disease. Preterm infants may be at risk in later life of metabolic complications through increased and aberrant adiposity.

Adipose Tissue↗

Magnetic resonance imaging of the knee with ultrashort TE pulse sequences.

BACKGROUND: We wished to assess the feasibility of imaging the knee with ultrashort TE (UTE) pulse sequences. SUBJECTS AND METHODS: Five volunteers and 16 patients were studied with UTE (TE=0.08 ms) sequences including later echoes. Conventional fat-suppressed images and difference images were also produced by subtracting a later echo from the first. Gadodiamide enhancement was used. RESULTS: High signal was obtained in tendons, ligaments, menisci and periosteum. Normal contrast enhancement was seen in these structures. Deep and superficial layers were seen in the articular cartilage. Cartilage defects were identified. The red zone could be differentiated from the white zone of the meniscus. Meniscal tears and degeneration were observed with low signal on subtraction images. Enhancement was seen within the anterior and posterior cruciate ligaments and associated scar tissue. CONCLUSION: Ultrashort TE imaging provides new options to visualize anatomy, manipulate conspicuity, observe contrast enhancement and demonstrate disease of the knee.

Adult↗

Prior knowledge for time domain quantification of in vivo brain or liver 31P MR spectra.

Prior knowledge is required when quantifying in vivo (31)P magnetic resonance spectra from the brain or liver. The prior knowledge system we have used models both the phosphomonoester and phosphodiester resonances as two peaks of equal linewidth and fixed relative chemical shift. The analysis of the data is carried out in the time domain, which allows the broad component of the spectra to be modelled. This prior knowledge method has been tested for analysis of in vivo (31)P MR spectra from the liver and brain and gives results consistent with other methods that are also used to analyse the spectra, but with reduced variability. This technique may be utilized for studies requiring serial MR spectroscopy examinations, before and after patient treatment.

Algorithms↗

The relationship of in vivo 31P MR spectroscopy to histology in chronic hepatitis C.

Liver biopsy remains the gold standard for characterizing diffuse liver disease and is associated with significant morbidity and, rarely, mortality. Our aim was to investigate whether a noninvasive technique, in vivo phosphorus 31 ((31)P)-magnetic resonance spectroscopy (MRS), could be used to assess the severity of hepatitis C virus (HCV)-related liver disease. Fifteen healthy controls and 48 patients with biopsy-proven HCV-related liver disease were studied prospectively. Based on their histologic fibrosis (F) and necroinflammatory (NI) scores, patients were divided into mild hepatitis (F or= 4/18), and cirrhosis (F = 6/6). Hepatic (31)P MR spectra were obtained using a 1.5-T spectroscopy system. Quantitation of the (31)P signals was performed in the time domain using the Advanced MAgnetic RESonance algorithm. There was a monotonic increase in the mean +/- 1 standard error phosphomonoester (PME) to phosphodiester (PDE) ratios for the control, mild disease, moderate disease, and cirrhosis groups: 0.15 +/- 0.01, 0.18 +/- 0.02, 0.25 +/- 0.02, 0.38 +/- 0.04, respectively (ANOVA, P <.001). An 80% sensitivity and specificity was achieved when using a PME/PDE ratio less than or equal to 0.2 to denote mild hepatitis and a corresponding ratio greater than or equal to 0.3 to denote cirrhosis. No other significant spectral changes were observed. In conclusion, (31)P MRS can separate mild from moderate disease and these 2 groups from cirrhosis. The ability to differentiate these populations of patients has therapeutic implications and (31)P MRS, in some situations, would not only complement a liver biopsy but could replace it and be of particular value in assessing disease progression.

Adult↗

Carbohydrate-induced manipulation of insulin sensitivity independently of intramyocellular lipids.

Subjects with insulin resistance have been shown to have higher storage levels of intramyocellular lipid (IMCL) than their insulin-sensitive counterparts. It has been proposed that elevated IMCL stores may be the main cause of insulin resistance. The aim of the present study was to ascertain whether there is a causal relationship between IMCL storage and insulin resistance. IMCL storage was assessed using magnetic resonance spectroscopy and insulin sensitivity was assessed by performing an oral glucose tolerance test. A 4-week intervention of reduction of dietary glycaemic index was used to manipulate insulin sensitivity in a cohort of healthy volunteers; the effects of this intervention on IMCL were measured after 4 weeks of intervention. Significant improvements in the insulin sensitivity index occurred following the dietary intervention (baseline 7.8 (sem 1.11) v. post-intervention 9.7 (sem 1.11), P=0.02). However, there were no changes in IMCL storage levels, suggesting that insulin sensitivity can be manipulated independently of IMCL. This suggests that in healthy volunteers, insulin sensitivity is independent of IMCL storage and the high storage levels that have been found in insulin-resistant subjects may occur as a consequence rather than a cause of insulin resistance.

Adult↗