Preterm infants' early growth and brain white matter maturation at term age.

BACKGROUND: Normal intrauterine conditions are essential to normal brain growth and development; premature birth and growth restriction can interrupt brain maturation. Maturation processes can be studied using diffusion tensor imaging. OBJECTIVE: The aim of this study was to use tract-based spatial statistics to assess the effect that early postnatal growth from birth to 40 gestational weeks has on brain white matter maturation. MATERIALS AND METHODS: A total of 36 preterm infants were accepted in the study. Postnatal growth was assessed by weight, length and head circumference. Birth weight z-score and gestational age were used as confounding covariates. RESULTS: Head circumference catch-up growth was associated with less mature diffusion parameters (P < 0.05). No significant associations were observed between weight or length growth and diffusion parameters. CONCLUSION: Growth-restricted infants seem to have delayed brain maturation that is not fully compensated at term, despite catch-up growth.

Measurement of brown adipose tissue mass using a novel dual-echo magnetic resonance imaging approach: a validation study.

OBJECTIVE: The aim of this study was to evaluate and validate magnetic resonance imaging (MRI) for the visualization and quantification of brown adipose tissue (BAT) in vivo in a rat model. We hypothesized that, based on differences in tissue water and lipid content, MRI could reliably differentiate between BAT and white adipose tissue (WAT) and could therefore be a possible alternative for (18)F-Fluorodeoxyglucose Positron Emission Tomography ((18)FDG-PET), the current gold standard for non-invasive BAT quantification. MATERIALS/METHODS: Eleven rats were studied using both (18)FDG-PET/CT and MRI (1.5 T). A dual echo (in-and-out-of-phase) sequence was used, both with and without spectral presaturation inversion recovery (SPIR) fat suppression (DUAL-SPIR) to visualize BAT, after which all BAT was surgically excised. The BAT volume measurements obtained via (18)FDG-PET/CT and DUAL-SPIR MR were quantitatively compared with the histological findings. All study protocols were reviewed and approved by the local ethics committee. RESULTS: The BAT mass measurements that were obtained using DUAL-SPIR MR subtraction images correlated better with the histological findings (P=0.017, R=0.89) than did the measurements obtained using (18)FDG-PET/CT (P=0.78, R=0.15), regardless of the BAT metabolic activation state. Additionally, the basic feasibility of the DUAL-SPIR method was demonstrated in three human pilot subjects. CONCLUSIONS: This study demonstrates the potential for MRI to reliably detect and quantify BAT in vivo. MRI can provide information beyond that provided by (18)FDG-PET imaging, and its ability to detect BAT is independent of its metabolic activation state. Additionally, MRI is a low-cost alternative that does not require radiation.

Effect of antenatal growth on brain white matter maturation in preterm infants at term using tract-based spatial statistics.

BACKGROUND: White matter maturation of infants can be studied using diffusion tensor imaging (DTI). DTI of the white matter of the infant brain provides the best available clinical measures of brain tissue organisation and integrity. OBJECTIVE: The purpose of this study was to compare white matter maturation between preterm infants born small for gestational age (SGA) and preterms with weight appropriate for gestational age (AGA) at birth. MATERIALS AND METHODS: A total of 36 preterm infants were enrolled in the study (SGA, n = 9). A rater-independent method called tract-based spatial statistics (TBSS) was used to assess white matter maturation. RESULTS: When measured by TBSS, the AGA infants showed higher fractional anisotrophy values in several white matter tracts than the SGA infants. Areas with significant differences included anterior thalamic radiation, corticospinal tract, forceps major and minor, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, superior longitudinal fasciculus, uncinate fasciculus, and superior longitudinal fasciculus (temporal part). No significant difference was found for mean diffusivity. CONCLUSION: As an objective and user-independent method, TBSS confirmed that preterm infants with impaired antenatal growth have impaired white matter maturation compared to preterm infants with normal antenatal growth. The differences were mainly detected in radiations that are myelinated first.

Fractional anisotropy and mean diffusivity parameters of the brain white matter tracts in preterm infants: reproducibility of region-of-interest measurements.

BACKGROUND: Diffusion tensor parameters can be analysed by fitting regions of interest (ROIs) to selected brain structures. The clinical usefulness of these measurements is influenced by their reproducibility and validity. OBJECTIVE: To investigate the reproducibility of fractional anisotropy (FA) and mean diffusivity (MD) measurements. MATERIAL AND METHODS: Seventy-six infants were imaged once at term-equivalent age. We measured several brain regions. Reproducibility was assessed using intraclass correlation coefficient and Bland-Altman method. RESULTS: Intra-observer reproducibility was excellent for FA in the calcarine cortex (right) and frontal white matter (left), and for MD in the corpus callosum (anterior), internal capsule, corona radiata, putamen, frontal white matter, optic radiation (left), thalamus (right) and calcarine cortex (right). Inter-observer reproducibility was excellent for FA in the corpus callosum (posterior) and for MD in the internal capsule and corona radiata (right). Inter-observer reproducibility was poor for FA in frontal and posterior white matter (right) and for MD in the inferior colliculus (right). Reproducibility was fair to good in other areas. The Bland-Altman plots showed no considerable bias, and variance was independent of the mean value. CONCLUSION: Reproducibility of ROI measurement was fair to good for both FA and MD.

Liver and pancreatic fat content and metabolism in healthy monozygotic twins with discordant physical activity.

BACKGROUND & AIMS: Ectopic fat in muscle and liver is linked to obesity and type 2 diabetes. Recently, pancreatic lipid accumulation has also been associated with ß-cell dysfunction and reduced insulin production, leading to the development of type 2 diabetes. Physical exercise training has been shown to attenuate ß-cell dysfunction in patients, but little is known about its effects on pancreatic and hepatic fat accumulation. In this study, we validated in-vivo proton magnetic resonance spectroscopy ((1)H MRS) in pancreatic fat measurement with biochemical measurements in a pig model. Thereafter, the effects of increased physical activity on the amounts of pancreatic and liver fat were studied in eight monozygotic twin pairs who have discordant physical activity and fitness. METHODS: Pancreatic fat content was studied in 15 pigs using (1)H MRS and/or biochemical analyses. In addition, liver and pancreatic fat were assessed using (1)H MRS in eight monozygotic male twin pairs with 18% mean difference in VO(2max) between the twin brothers. RESULTS: Twins with higher physical fitness had 23% less liver fat (1.3±1.3% vs. 2.1±2.6%, p=0.022) but no such difference was observed in the pancreatic fat (8.2±9.3% vs. 9.8±8.5%, respectively, p=0.3). Hepatic fat content was inversely associated with VO(2max). A positive association was found between pancreatic and liver fat contents (ß=5.18, p=0.012). Pancreatic fat content was also associated with insulin sensitivity indexes and plasma adiponectin and glutamyltransferase concentrations. CONCLUSIONS: Pancreatic fat content is associated with insulin resistance and hepatic fat content. An active lifestyle seems to beneficially influence hepatic fat metabolism.

Nonalcoholic fatty liver disease: rapid evaluation of liver fat content with in-phase and out-of-phase MR imaging.

PURPOSE: To evaluate in-phase and out-of-phase magnetic resonance (MR) imaging in the estimation of liver fat content (LFC) in patients with nonalcoholic fatty liver disease (NAFLD), with hydrogen ((1)H) MR spectroscopy as the reference standard. MATERIALS AND METHODS: Written informed consent was obtained from all subjects, and the local ethics committee approved this prospective study protocol. A total of 33 patients with type 2 diabetes mellitus who were at high risk for NAFLD (23 men, 10 women; overall mean age, 62.8 years +/- 8.3 [standard deviation]; age range, 48-77 years) underwent 1.5-T MR imaging with (1)H MR spectroscopy and in-phase and out-of-phase imaging of the liver. Three fat indexes were calculated from the signal intensity (SI) measured on the images. Two radiologists independently graded SI changes between in-phase and out-of-phase images by means of visual inspection. The Pearson correlation coefficient was used to study the relationship between the obtained parameters of SI change and LFC measured with (1)H MR spectroscopy. RESULTS: Fat indexes calculated from in-phase and out-of-phase images correlated linearly with LFC measured with (1)H MR spectroscopy (P < .001, r = 0.94-0.96) and were superior (P = .004) to visual estimates (P < .001, r = 0.88). The simple difference in SI between in-phase and out-of-phase images was used to calculate the fat index. An intercept of the regression line with the x-axis was observed at 5.1%, discriminating between normal and elevated LFC with high sensitivity (95%) and specificity (98%). CONCLUSION: In-phase and out-of-phase imaging can be used to rapidly estimate the LFC in patients with NAFLD. The cutoff value of 5.1% enables objective rapid and reliable discrimination of normal LFC from elevated LFC.

Inverse association between liver fat content and hepatic glucose uptake in patients with type 2 diabetes mellitus.

The objective of this research was to study (1) the mutual relationship between liver fat content (LFC) and hepatic glucose uptake (HGU) in patients with type 2 diabetes mellitus and (2) the relationship between changes in LFC and HGU uptake induced by rosiglitazone in these patients. Liver fat was measured with proton magnetic resonance spectroscopy and insulin-stimulated HGU with [(18)F]-labeled 2-fluoro-2-deoxyglucose positron emission tomography in 54 patients with type 2 diabetes mellitus and 8 healthy subjects. Measurements were repeated in diabetic patients after a 16-week intervention period with rosiglitazone (n = 27) or placebo (n = 27). Patients with diabetes had lower HGU (24.5 +/- 14.2 vs 35.6 +/- 9.7 micromol/[kg min], P < .01) and higher LFC (10.9% +/- 9.2% vs 2.5% +/- 1.4%, P < .001) compared with healthy subjects. Liver fat was inversely associated with HGU (r = -0.31, P < .05), but more strongly with whole-body insulin sensitivity and adiponectin levels. Rosiglitazone treatment reduced liver fat by 24.8% (P = .01 vs placebo) and increased HGU by 29.2% (P = .013 vs placebo). This decrease in LFC was best explained by the increment in suppression of nonesterified fatty acid levels during hyperinsulinemia (P < .001) and improved glycemic control (P = .034), but not by changes in HGU. A significant inverse relationship between LFC and HGU was observed, but changes were not related. This suggests that the beneficial effects of rosiglitazone on liver metabolism are indirect and can be partly explained by increased suppression of nonesterified fatty acid levels, leading to reduced liver fat.

Quantitative liver iron measurement by magnetic resonance imaging: in vitro and in vivo assessment of the liver to muscle signal intensity and the R2* methods.

PURPOSE: To evaluate the liver-to-muscle signal intensity and R2* methods to gain a transferable, clinical application for liver iron measurement. MATERIALS AND METHODS: Sixteen liver phantoms and 33 human subjects were examined using three 1.5-T MRI scanners from two different vendors. Phantom-to-muscle and liver-to-muscle signal intensity ratios were analyzed to determine MRI estimated phantom and hepatic iron concentration (M-PIC and M-HIC, respectively). R2* was calculated for the phantoms and the liver of human subjects. Seven patients' biochemical hepatic iron concentration was obtained. RESULTS: M-PIC and R2* results of three scanners correlated linearly to phantom iron concentrations (r=0.984 to 0.989 and r=0.972 to 0.981, respectively), and no significant difference between the scanners was found (P=.482 and P=.846, respectively) in vitro. The patients' R2* correlated linearly to M-HIC of the standard scanner (r=0.981). M-HIC values did not differ from those obtained from the biopsy specimens (P=.230). The difference in M-HIC was significant, but the difference in R2* was not significant between the scanners (P<.0001 and P=.505, respectively) in vivo. CONCLUSION: Both methods, M-HIC and R2*, are reliable iron concentration indicators with linear dependence on iron concentration in vivo and in vitro. The R2* method was found to be comparable among different scanners. Transferability testing is needed for the use of the methods at various scanners.

Myocardial triglyceride content and epicardial fat mass in human obesity: relationship to left ventricular function and serum free fatty acid levels.

CONTEXT AND OBJECTIVE: Ectopic fat accumulation within and around the myocardial wall has been implicated in the pathogenesis of heart disease in obesity. We evaluated myocardial and epicardial fat, left ventricular (LV) function, and metabolic risk factors in nine (five lean, four moderately obese) men. METHODS: Myocardial fat percent was quantified in the septum by proton magnetic resonance spectroscopy. Reproducibility was assessed by triplicate systolic and diastolic measurements. LV parameters and epicardial fat were determined by magnetic resonance imaging. Waist-to-hip ratio and liver enzymes (alanine transaminase) were used as surrogate markers of visceral and liver fat contents. RESULTS: Myocardial fat (2.1 +/- 0.5 vs. 0.8 +/- 0.1, P = 0.03) and epicardial fat (120 +/- 33 vs. 55 +/- 12 g, P = 0.08) were higher in obese than lean subjects. Individuals with above-median alanine transaminase values had a 4-fold elevation in myocardial fat. The coefficient of variation of repeated myocardial fat percent determinations was 17 +/- 3 and 23 +/- 3% in systole and diastole, respectively. Myocardial fat was correlated with free fatty acid (FFA) levels (r = 0.76; P = 0.017), epicardial fat (r = 0.69; P = 0.042), and waist-to-hip ratio (r = 0.70; P = 0.035), and it showed a tendency to associate positively with LV work. Epicardial fat was associated with peripheral vascular resistance (positively) and the cardiac index (negatively). FFA levels were significantly correlated with LV mass (r = 0.72; P = 0.030) and forward work (r = 0.74; P = 0.023). CONCLUSIONS/INTERPRETATION: The accumulation of triglyceride in and around the myocardium of moderately obese individuals is significant, and it is related to FFA exposure, generalized ectopic fat excess, and peripheral vascular resistance. These changes precede LV overload and hypertrophy.

Comparison of MRI and positron emission tomography for measuring myocardial perfusion reserve in healthy humans.

Myocardial perfusion reserve (MPR, defined as the ratio of the maximum myocardial blood flow (MBF) to the baseline) is an indicator of coronary artery disease and myocardial microvascular abnormalities. First-pass contrast-enhanced magnetic resonance imaging (CE-MRI) using gadolinium (Gd)-DTPA as a contrast agent (CA) has been used to assess MPR. Tracer kinetic models based on compartmental analysis of the CA uptake have been developed to provide quantitative measures of MBF by MRI. To study the accuracy of Gd-DTPA first-pass MRI and kinetic modeling for quantitative analysis of myocardial perfusion and MPR during dipyridamole infusion, we conducted a comparison with positron emission tomography (PET) in 18 healthy males (age = 40 +/- 14 years). Five planes were acquired at every second heartbeat with a 1.5T scanner using a saturation recovery turboFLASH sequence. A perfusion-related parameter, the unidirectional influx constant (Ki), was computed in three coronary artery territories. There was a significant correlation for both dipyridamole-induced flow (0.70, P = 0.001) and MPR (0.48, P = 0.04) between MRI and PET. However, we noticed that MRI provided lower MPR values compared to PET (2.5 +/- 1.0 vs. 4.3 +/- 1.8). We conclude that MRI supplemented with tracer kinetic modeling can be used to quantify myocardial perfusion.

T1rho Dispersion profile of rat tissues in vitro at very low locking fields.

The purpose of this study was to show the T(1rho) dispersion profile in various rat tissues (liver, brain, spleen, kidney, heart and skeletal muscle) at low (0.1 T) B(0) field at very low locking field B1, starting from 10 microT. The T(1rho) dispersion profile showed a quite similar pattern in all tissues. The highest R(1rho) relaxation rates were seen in the liver and muscle followed by the heart, whereas the values for spleen, kidney and brain were rather similar. The greatest difference between R2 relaxation rate and R(1rho) relaxation rate at B1=10 microT was seen in the liver and muscle. The steepest slope for a dispersion curve was seen in the muscle. The value of T(1rho) approximately approached the value of T2 when the locking field B1 approached 0. Except for the liver, the calculated apparent relaxation rate R2' was slightly larger than the calculated one. The potential value of T(1rho) imaging is to combine high R1 contrast of low-field imaging with the high signal-to-noise ratio (SNR) of high static field imaging. T(1rho) relaxation and dispersion data presented in the current study help to optimize the rotating-frame MR imaging.

Liver steatosis coexists with myocardial insulin resistance and coronary dysfunction in patients with type 2 diabetes.

Nonalcoholic fatty liver (NAFL) is a common comorbidity in patients with type 2 diabetes and links to the risk of coronary syndromes. The aim was to determine the manifestations of metabolic syndrome in different organs in patients with liver steatosis. We studied 55 type 2 diabetic patients with coronary artery disease using positron emission tomography. Myocardial perfusion was measured with [15O]H2O and myocardial and skeletal muscle glucose uptake with 2-deoxy-2-[18F]fluoro-D-glucose during hyperinsulinemic euglycemia. Liver fat content was determined by magnetic resonance proton spectroscopy. Patients were divided on the basis of their median (8%) into two groups with low (4.6 +/- 2.0%) and high (17.4 +/- 8.0%) liver fat content. The groups were well matched for age, BMI, and fasting plasma glucose. In addition to insulin resistance at the whole body level (P = 0.012) and muscle (P = 0.002), the high liver fat group had lower insulin-stimulated myocardial glucose uptake (P = 0.040) and glucose extraction rate (P = 0.0006) compared with the low liver fat group. In multiple regression analysis, liver fat content was the most significant explanatory variable for myocardial insulin resistance. In addition, the high liver fat group had increased concentrations of high sensitivity C-reactive protein, soluble forms of E-selectin, vascular adhesion protein-1, and intercellular adhesion molecule-1 (P < 0.05) and lower coronary flow reserve (P = 0.02) compared with the low liver fat group. In conclusion, in patients with type 2 diabetes and coronary artery disease, liver fat content is a novel independent indicator of myocardial insulin resistance and reduced coronary functional capacity. Further studies will reveal the effect of hepatic fat reduction on myocardial metabolism and coronary function.

Quantitative HMRS and MRI volumetry indicate neuronal damage in the hippocampus of children with focal epilepsy and infrequent seizures.

PURPOSE: Seizures induce progressive morphologic and functional changes in particular in the hippocampus, but whether and at what stage the hippocampus is affected in children with focal, temporal, nonintractable epilepsy is poorly known. We have now studied eventual metabolic and volume changes in the hippocampus of children with nonsymptomatic focal epilepsy taking antiepileptic medication (AEDs) but still having infrequent seizures. METHODS: Quantitative proton magnetic resonance spectroscopy ((1)HMRS) and volumetric MRI were used to study the hippocampal region of 11 pediatric outpatients (age 10 to 17 years) with cryptogenic localization-related epilepsy, and eight healthy volunteers (age 9 to 16 years) served as controls. The spectra were obtained bilaterally from the hippocampi by using the 1.5-T MR imager. The spectral resonance lines of N-acetyl group (NA), creatine and phosphocreatine group (Cr), choline-containing compounds (Cho), and myoinositol (mI) were analyzed quantitatively. The volume of the hippocampus was semiautomatically calculated. RESULTS: The mean concentration of NA was significantly decreased both in the focus side (9.02 +/- 2.00 mM) and in the nonfocus side (8.88 +/- 2.09 mM) of the patients compared with the controls (10.76 +/- 1.86 mM), in particular if the children had a history of generalized tonic-clonic seizures. The mean concentrations of Cho, Cr, and mI did not differ significantly between the patients and controls. Moreover, the mean hippocampal volume of the focus side of patients was significantly reduced compared with that of the controls. CONCLUSIONS: Metabolic changes in hippocampi were detected in children with nonsymptomatic localization-related epilepsy and infrequent seizures. Reduced NA could reflect neuronal metabolic dysfunction and/or neuronal damage, as indicated by our volumetric findings.