Toward nonparametric diffusion- T1 characterization of crossing fibers in the human brain.

PURPOSE: To estimate T1 for each distinct fiber population within voxels containing multiple brain tissue types. METHODS: A diffusion- T1 correlation experiment was carried out in an in vivo human brain using tensor-valued diffusion encoding and multiple repetition times. The acquired data were inverted using a Monte Carlo algorithm that retrieves nonparametric distributions P(D,R1) of diffusion tensors and longitudinal relaxation rates R1=1/T1 . Orientation distribution functions (ODFs) of the highly anisotropic components of P(D,R1) were defined to visualize orientation-specific diffusion-relaxation properties. Finally, Monte Carlo density-peak clustering (MC-DPC) was performed to quantify fiber-specific features and investigate microstructural differences between white matter fiber bundles. RESULTS: Parameter maps corresponding to P(D,R1) 's statistical descriptors were obtained, exhibiting the expected R1 contrast between brain tissue types. Our ODFs recovered local orientations consistent with the known anatomy and indicated differences in R1 between major crossing fiber bundles. These differences, confirmed by MC-DPC, were in qualitative agreement with previous model-based works but seem biased by the limitations of our current experimental setup. CONCLUSIONS: Our Monte Carlo framework enables the nonparametric estimation of fiber-specific diffusion- T1 features, thereby showing potential for characterizing developmental or pathological changes in T1 within a given fiber bundle, and for investigating interbundle T1 differences.

Prognostic impact of right ventricular mass change in patients with idiopathic pulmonary arterial hypertension.

BACKGROUND: Compensatory remodelling i.e. increased right ventricular (RV) mass frequently occurs as an adaptive response to the chronic pressure overload to maintain contractile function. The prognostic value of the serial change in RV mass is unclear. AIM: The aim of our study was to examine the longitudinal changes in RV mass and survival in patients with idiopathic pulmonary arterial hypertension (IPAH). METHODS: Consecutive newly diagnosed IPAH patients >18 years old were prospectively recruited from a tertiary referral center. All recruited patients were maintained on guideline-based therapy and were followed up with echocardiography and cardiac magnetic resonance for 2 years. RESULTS: Serial measures of RV mass revealed that survivors appeared to have had a compensatory increase in RV mass, which constituted adaptive RV remodelling early in the disease process, which was not seen in those who died. (Hazard ratio of 0.932, 95% confidence interval 0.893-0.973, p = 0.001). CONCLUSION: This study shows that serial measurement of RV mass in IPAH patients provides prognostic information. RV mass regression is an ominous prognostic sign, which may predict early mortality in these patients.

A modified echocardiographic approach improves reliability of superior vena caval flow quantification.

OBJECTIVE: To assess accuracy and repeatability of a modified echocardiographic approach to quantify superior vena cava (SVC) flow volume that uses a short-axis view to directly measure SVC area and a suprasternal view to measure flow velocity, both at the level of the right pulmonary artery. SETTING: Three tertiary-level neonatal intensive care units. DESIGN: This was a multicentre, prospective, observational study. Accuracy of the traditional and modified approach was first assessed by comparing echo measurements according to both techniques with Phase contrast MRI (PCMRI) assessments, in a cohort of 10 neonates. In a second cohort of 40 neonates, intraobserver scan-rescan repeatability and interobserver analysis-reanalysis repeatability were assessed by repeated SVC flow echo measurements, according to both techniques. RESULTS: The traditional echocardiographic approach to assessment of SVC flow had a moderate agreement with PCMRI (r2 0.259), a scan-rescan intraobserver repeatability index (RI) of 37% (limits of agreement (LOA) -47/+51 mL/kg/min) and an interobserver analysis-reanalysis RI of 31% (LOA -38/+40 mL/kg/min). The modified approach showed a stronger agreement with PCMRI (r2 0.775), an improved intraobserver scan-rescan repeatability (RI 22%, LOA -24/+18 mL/kg/min) and improved interobserver analysis-reanalysis repeatability (RI 18%, LOA -18/+20 mL/kg/min). CONCLUSIONS: Echocardiographic assessment of SVC flow volume by tracing area from a short-axis view and measuring velocity-time integral from a suprasternal view offered an improvement in accuracy and repeatability, building on the traditional approach previously described.

Nutritional Evaluation and Optimisation in Neonates: a randomized, double-blind controlled trial of amino acid regimen and intravenous lipid composition in preterm parenteral nutrition.

BACKGROUND: Parenteral nutrition is central to the care of very immature infants. Current international recommendations favor higher amino acid intakes and fish oil-containing lipid emulsions. OBJECTIVE: The aim of this trial was to compare 1) the effects of high [immediate recommended daily intake (Imm-RDI)] and low [incremental introduction of amino acids (Inc-AAs)] parenteral amino acid delivery within 24 h of birth on body composition and 2) the effect of a multicomponent lipid emulsion containing 30% soybean oil, 30% medium-chain triglycerides, 25% olive oil, and 15% fish oil (SMOF) with that of soybean oil (SO)-based lipid emulsion on intrahepatocellular lipid (IHCL) content. DESIGN: We conducted a 2-by-2 factorial, double-blind, multicenter randomized controlled trial. RESULTS: We randomly assigned 168 infants born at <31 wk of gestation. We evaluated outcomes at term in 133 infants. There were no significant differences between Imm-RDI and Inc-AA groups for nonadipose mass [adjusted mean difference: 1.0 g (95% CI: -108, 111 g; P = 0.98)] or between SMOF and SO groups for IHCL [adjusted mean SMOF:SO ratio: 1.1 (95% CI: 0.8, 1.6; P = 0.58]. SMOF does not affect IHCL content. There was a significant interaction (P = 0.05) between the 2 interventions for nonadipose mass. There were no significant interactions between group differences for either primary outcome measure after adjusting for additional confounders. Imm-RDI infants were more likely than Inc-AA infants to have blood urea nitrogen concentrations >7 mmol/L or >10 mmol/L, respectively (75% compared with 49%, P < 0.01; 49% compared with 18%, P < 0.01). Head circumference at term was smaller in the Imm-RDI group [mean difference: -0.8 cm (95% CI: -1.5, -0.1 cm; P = 0.02)]. There were no significant differences in any prespecified secondary outcomes, including adiposity, liver function tests, incidence of conjugated hyperbilirubinemia, weight, length, mortality, and brain volumes. CONCLUSION: Imm-RDI of parenteral amino acids does not benefit body composition or growth to term and may be harmful. This trial was registered at www.isrctn.com as ISRCTN29665319 and at eudract.ema.europa.eu as EudraCT 2009-016731-34.

Pulmonary Artery Stiffness Is Independently Associated with Right Ventricular Mass and Function: A Cardiac MR Imaging Study.

Purpose To determine the relationship between pulmonary artery (PA) stiffness and both right ventricular (RV) mass and function with cardiac magnetic resonance (MR) imaging. Materials and Methods The study was approved by the local research ethics committee, and all participants gave written informed consent. Cardiac MR imaging was performed at 1.5 T in 156 healthy volunteers (63% women; age range, 19-61 years; mean age, 36.1 years). High-temporal-resolution phase-contrast imaging was performed in the main and right PAs. Pulmonary pulse wave velocity (PWV) was determined by the interval between arterial systolic upslopes. RV function was assessed with feature tracking to derive peak systolic strain and strain rate, as well as peak early-diastolic strain rate. RV volumes, ejection fraction (RVEF), and mass were measured from the cine images. The association of pulmonary PWV with RV function and mass was quantified with univariate linear regression. Interstudy repeatability was assessed with intraclass correlation. Results The repeatability coefficient for pulmonary PWV was 0.96. Increases in pulmonary PWV and RVEF were associated with increases in age (r = 0.32, P < .001 and r = 0.18, P = .025, respectively). After adjusting for age (P = .090), body surface area (P = .073), and sex (P = .005), pulmonary PWV demonstrated an independent positive association with RVEF (r = 0.34, P = .026). Significant associations were also seen with RV mass (r = 0.41, P = .004), RV radial strain (r = 0.38, P = .022), and strain rate (r = 0.35, P = .002), and independent negative associations were seen with radial (r = 0.27, P = .003), longitudinal (r = 0.40, P = .007), and circumferential (r = 0.31, P = .005) peak early-diastolic strain rate with the same covariates. Conclusion Pulmonary PWV is reliably assessed with cardiac MR imaging. In subjects with no known cardiovascular disease, increasing PA stiffness is associated with increasing age and is also moderately associated with both RV mass and function after controlling for age, body surface area, and sex. (©) RSNA, 2016 Online supplemental material is available for this article.

Link Between Increased Satiety Gut Hormones and Reduced Food Reward After Gastric Bypass Surgery for Obesity.

CONTEXT: Roux-en-Y gastric bypass (RYGB) surgery is an effective long-term intervention for weight loss maintenance, reducing appetite, and also food reward, via unclear mechanisms. OBJECTIVE: To investigate the role of elevated satiety gut hormones after RYGB, we examined food hedonic-reward responses after their acute post-prandial suppression. DESIGN: These were randomized, placebo-controlled, double-blind, crossover experimental medicine studies. PATIENTS: Two groups, more than 5 months after RYGB for obesity (n = 7-11), compared with nonobese controls (n = 10), or patients after gastric banding (BAND) surgery (n = 9) participated in the studies. INTERVENTION: Studies were performed after acute administration of the somatostatin analog octreotide or saline. In one study, patients after RYGB, and nonobese controls, performed a behavioral progressive ratio task for chocolate sweets. In another study, patients after RYGB, and controls after BAND surgery, performed a functional magnetic resonance imaging food picture evaluation task. MAIN OUTCOME MEASURES: Octreotide increased both appetitive food reward (breakpoint) in the progressive ratio task (n = 9), and food appeal (n = 9) and reward system blood oxygen level-dependent signal (n = 7) in the functional magnetic resonance imaging task, in the RYGB group, but not in the control groups. RESULTS: Octreotide suppressed postprandial plasma peptide YY, glucagon-like peptide-1, and fibroblast growth factor-19 after RYGB. The reduction in plasma peptide YY with octreotide positively correlated with the increase in brain reward system blood oxygen level-dependent signal in RYGB/BAND subjects, with a similar trend for glucagon-like peptide-1. CONCLUSIONS: Enhanced satiety gut hormone responses after RYGB may be a causative mechanism by which anatomical alterations of the gut in obesity surgery modify behavioral and brain reward responses to food.

Precursors of Hypertensive Heart Phenotype Develop in Healthy Adults: A High-Resolution 3D MRI Study.

OBJECTIVES: This study used high-resolution 3-dimensional cardiac magnetic resonance to define the anatomical and functional left ventricular (LV) properties associated with increasing systolic blood pressure (SBP) in a drug-naïve cohort. BACKGROUND: LV hypertrophy and remodeling occur in response to hemodynamic stress but little is known about how these phenotypic changes are initiated in the general population. METHODS: In this study, 1,258 volunteers (54% women, mean age 40.6 ± 12.8 years) without self-reported cardiovascular disease underwent 3-dimensional cardiac magnetic resonance combined with computational modeling. The relationship between SBP and wall thickness (WT), relative WT, end-systolic wall stress (WS), and fractional wall thickening were analyzed using 3-dimensional regression models adjusted for body surface area, sex, race, age, and multiple testing. Significantly associated points in the LV model (p < 0.05) were identified and the relationship with SBP reported as mean ß coefficients. RESULTS: There was a continuous relationship between SBP and asymmetric concentric hypertrophic adaptation of the septum and anterior wall that was associated with normalization of wall stress. In the lateral wall an increase in wall stress with rising SBP was not balanced by a commensurate hypertrophic relationship. In normotensives, SBP was positively associated with WT (ß = 0.09) and relative WT (ß = 0.07) in the septal and anterior walls, and this regional hypertrophic relationship was progressively stronger among pre-hypertensives (ß = 0.10) and hypertensives (ß = 0.30). CONCLUSIONS: These findings show that the precursors of the hypertensive heart phenotype can be traced to healthy normotensive adults and that an independent and continuous relationship exists between adverse LV remodeling and SBP in a low-risk population. These adaptations show distinct regional variations with concentric hypertrophy of the septum and eccentric hypertrophy of the lateral wall, which challenge conventional classifications of LV remodeling.

Cardiovascular magnetic resonance of cardiac function and myocardial mass in preterm infants: a preliminary study of the impact of patent ductus arteriosus.

BACKGROUND: Many pathologies seen in the preterm population are associated with abnormal blood supply, yet robust evaluation of preterm cardiac function is scarce and consequently normative ranges in this population are limited. The aim of this study was to quantify and validate left ventricular dimension and function in preterm infants using cardiovascular magnetic resonance (CMR). An initial investigation of the impact of the common congenital defect patent ductus arteriosus (PDA) was then carried out. METHODS: Steady State Free Procession short axis stacks were acquired. Normative ranges of left ventricular end diastolic volume (EDV), stroke volume (SV), left ventricular output (LVO), ejection fraction (EF), left ventricular (LV) mass, wall thickness and fractional thickening were determined in "healthy" (control) neonates. Left ventricular parameters were then investigated in PDA infants. Unpaired student t-tests compared the 2 groups. Multiple linear regression analysis assessed impact of shunt volume in PDA infants, p-value ≤ 0.05 being significant. RESULTS: 29 control infants median (range) corrected gestational age at scan 34+6(31+1-39+3) weeks were scanned. EDV, SV, LVO, LV mass normalized by weight and EF were shown to decrease with increasing corrected gestational age (cGA) in controls. In 16 PDA infants (cGA 30+3(27+3-36+1) weeks) left ventricular dimension and output were significantly increased, yet there was no significant difference in ejection fraction and fractional thickening between the two groups. A significant association between shunt volume and increased left ventricular mass correcting for postnatal age and corrected gestational age existed. CONCLUSION: CMR assessment of left ventricular function has been validated in neonates, providing more robust normative ranges of left ventricular dimension and function in this population. Initial investigation of PDA infants would suggest that function is relatively maintained.

Preterm nutritional intake and MRI phenotype at term age: a prospective observational study.

OBJECTIVE: To describe (1) the relationship between nutrition and the preterm-at-term infant phenotype, (2) phenotypic differences between preterm-at-term infants and healthy term born infants and (3) relationships between somatic and brain MRI outcomes. DESIGN: Prospective observational study. SETTING: UK tertiary neonatal unit. PARTICIPANTS: Preterm infants (<32 weeks gestation) (n=22) and healthy term infants (n=39) MAIN OUTCOME MEASURES: Preterm nutrient intake; total and regional adipose tissue (AT) depot volumes; brain volume and proximal cerebral arterial vessel tortuosity (CAVT) in preterm infants and in term infants. RESULTS: Preterm nutrition was deficient in protein and high in carbohydrate and fat. Preterm nutrition was not related to AT volumes, brain volume or proximal CAVT score; a positive association was noted between human milk intake and proximal CAVT score (r=0.44, p=0.05). In comparison to term infants, preterm infants had increased total adiposity, comparable brain volumes and reduced proximal CAVT scores. There was a significant negative correlation between deep subcutaneous abdominal AT volume and brain volume in preterm infants (r=-0.58, p=0.01). CONCLUSIONS: Though there are significant phenotypic differences between preterm infants at term and term infants, preterm macronutrient intake does not appear to be a determinant. Our preliminary data suggest that (1) human milk may exert a beneficial effect on cerebral arterial vessel tortuosity and (2) there is a negative correlation between adiposity and brain volume in preterm infants at term. Further work is warranted to see if our findings can be replicated and to understand the causal mechanisms.

Ghrelin mimics fasting to enhance human hedonic, orbitofrontal cortex, and hippocampal responses to food.

BACKGROUND: Ghrelin, which is a stomach-derived hormone, increases with fasting and energy restriction and may influence eating behaviors through brain hedonic reward-cognitive systems. Therefore, changes in plasma ghrelin might mediate counter-regulatory responses to a negative energy balance through changes in food hedonics. OBJECTIVE: We investigated whether ghrelin administration (exogenous hyperghrelinemia) mimics effects of fasting (endogenous hyperghrelinemia) on the hedonic response and activation of brain-reward systems to food. DESIGN: In a crossover design, 22 healthy, nonobese adults (17 men) underwent a functional magnetic resonance imaging (fMRI) food-picture evaluation task after a 16-h overnight fast (Fasted-Saline) or after eating breakfast 95 min before scanning (730 kcal, 14% protein, 31% fat, and 55% carbohydrate) and receiving a saline (Fed-Saline) or acyl ghrelin (Fed-Ghrelin) subcutaneous injection before scanning. One male subject was excluded from the fMRI analysis because of excess head motion, which left 21 subjects with brain-activation data. RESULTS: Compared with the Fed-Saline visit, both ghrelin administration to fed subjects (Fed-Ghrelin) and fasting (Fasted-Saline) significantly increased the appeal of high-energy foods and associated orbitofrontal cortex activation. Both fasting and ghrelin administration also increased hippocampus activation to high-energy- and low-energy-food pictures. These similar effects of endogenous and exogenous hyperghrelinemia were not explicable by consistent changes in glucose, insulin, peptide YY, and glucagon-like peptide-1. Neither ghrelin administration nor fasting had any significant effect on nucleus accumbens, caudate, anterior insula, or amygdala activation during the food-evaluation task or on auditory, motor, or visual cortex activation during a control task. CONCLUSIONS: Ghrelin administration and fasting have similar acute stimulatory effects on hedonic responses and the activation of corticolimbic reward-cognitive systems during food evaluations. Similar effects of recurrent or chronic hyperghrelinemia on an anticipatory food reward may contribute to the negative impact of skipping breakfast on dietary habits and body weight and the long-term failure of energy restriction for weight loss.

Adiposity and hepatic lipid in healthy full-term, breastfed, and formula-fed human infants: a prospective short-term longitudinal cohort study.

BACKGROUND: The effect of mode of infant feeding on adiposity deposition is not fully understood. OBJECTIVE: The objective was to test the hypothesis that differences in total and regional adipose tissue content and intrahepatocellular lipid (IHCL) arise in early infancy between breast- and formula-fed infants and to describe longitudinal changes. DESIGN: This prospective longitudinal cohort study was performed in 2 hospitals in the United Kingdom. Healthy, full-term, appropriate weight-for-gestational age infants were recruited; adipose tissue volume and distribution were directly quantified by using whole-body magnetic resonance imaging; IHCL was assessed by in vivo proton magnetic resonance spectroscopy. Measurements were performed after birth (median age: 13 d) and at 6-12 wk of age. Method of infant feeding was recorded prospectively by using maternally completed feeding diaries. Breastfed was defined as >80% of feeds consisting of breast milk at both points; formula-fed was defined as >80% of feeds consisting of formula milk at both points. RESULTS: Longitudinal results were obtained from 70 infants (36 breastfed, 9 mixed-fed, and 25 formula-fed). No differences were found in total or regional adipose tissue or IHCL between breastfed and formula-fed infants. In pooled analyses including all feeding groups, IHCL and total adipose tissue approximately doubled between birth and 6-12 wk: IHCL after birth (median: 0.949; IQR: 0.521-1.711) and at 6-12 wk (1.828; 1.376-2.697; P < 0.001) and total adipose tissue after birth (0.749 L; 0.620-0.928 L) and at 6-12 wk (1.547 L; 1.332-1.790 L; P < 0.001). Increasing adiposity was characterized by greater relative increases in subcutaneous than in internal adipose tissue depots. CONCLUSIONS: No differences were detectable in adipose tissue or IHCL accretion between breastfed and formula-fed infants up to 2 mo. The substantial increase in IHCL seen over this period in both breastfed and formula-fed infants is a novel observation, which suggests that hepatic storage of lipids may be physiologic up to 2 mo. This trial was registered at www.clinicaltrials.gov as NCT02033005.

Population-based studies of myocardial hypertrophy: high resolution cardiovascular magnetic resonance atlases improve statistical power.

BACKGROUND: Cardiac phenotypes, such as left ventricular (LV) mass, demonstrate high heritability although most genes associated with these complex traits remain unidentified. Genome-wide association studies (GWAS) have relied on conventional 2D cardiovascular magnetic resonance (CMR) as the gold-standard for phenotyping. However this technique is insensitive to the regional variations in wall thickness which are often associated with left ventricular hypertrophy and require large cohorts to reach significance. Here we test whether automated cardiac phenotyping using high spatial resolution CMR atlases can achieve improved precision for mapping wall thickness in healthy populations and whether smaller sample sizes are required compared to conventional methods. METHODS: LV short-axis cine images were acquired in 138 healthy volunteers using standard 2D imaging and 3D high spatial resolution CMR. A multi-atlas technique was used to segment and co-register each image. The agreement between methods for end-diastolic volume and mass was made using Bland-Altman analysis in 20 subjects. The 3D and 2D segmentations of the LV were compared to manual labeling by the proportion of concordant voxels (Dice coefficient) and the distances separating corresponding points. Parametric and nonparametric data were analysed with paired t-tests and Wilcoxon signed-rank test respectively. Voxelwise power calculations used the interstudy variances of wall thickness. RESULTS: The 3D volumetric measurements showed no bias compared to 2D imaging. The segmented 3D images were more accurate than 2D images for defining the epicardium (Dice: 0.95 vs 0.93, P<0.001; mean error 1.3 mm vs 2.2 mm, P<0.001) and endocardium (Dice 0.95 vs 0.93, P<0.001; mean error 1.1 mm vs 2.0 mm, P<0.001). The 3D technique resulted in significant differences in wall thickness assessment at the base, septum and apex of the LV compared to 2D (P<0.001). Fewer subjects were required for 3D imaging to detect a 1 mm difference in wall thickness (72 vs 56, P<0.001). CONCLUSIONS: High spatial resolution CMR with automated phenotyping provides greater power for mapping wall thickness than conventional 2D imaging and enables a reduction in the sample size required for studies of environmental and genetic determinants of LV wall thickness.

Obese patients after gastric bypass surgery have lower brain-hedonic responses to food than after gastric banding.

OBJECTIVES: Roux-en-Y gastric bypass (RYGB) has greater efficacy for weight loss in obese patients than gastric banding (BAND) surgery. We hypothesise that this may result from different effects on food hedonics via physiological changes secondary to distinct gut anatomy manipulations. DESIGN: We used functional MRI, eating behaviour and hormonal phenotyping to compare body mass index (BMI)-matched unoperated controls and patients after RYGB and BAND surgery for obesity. RESULTS: Obese patients after RYGB had lower brain-hedonic responses to food than patients after BAND surgery. RYGB patients had lower activation than BAND patients in brain reward systems, particularly to high-calorie foods, including the orbitofrontal cortex, amygdala, caudate nucleus, nucleus accumbens and hippocampus. This was associated with lower palatability and appeal of high-calorie foods and healthier eating behaviour, including less fat intake, in RYGB compared with BAND patients and/or BMI-matched unoperated controls. These differences were not explicable by differences in hunger or psychological traits between the surgical groups, but anorexigenic plasma gut hormones (GLP-1 and PYY), plasma bile acids and symptoms of dumping syndrome were increased in RYGB patients. CONCLUSIONS: The identification of these differences in food hedonic responses as a result of altered gut anatomy/physiology provides a novel explanation for the more favourable long-term weight loss seen after RYGB than after BAND surgery, highlighting the importance of the gut-brain axis in the control of reward-based eating behaviour.

Validation study of the accuracy of echocardiographic measurements of systemic blood flow volume in newborn infants.

BACKGROUND: The echocardiographic assessment of circulatory function in sick newborn infants has the potential to improve patient care. However, measurements are prone to error and have not been sufficiently validated. Phase-contrast magnetic resonance imaging (MRI) provides highly validated measures of blood flow and has recently been applied to the newborn population. The aim of this study was to validate measures of left ventricular output and superior vena caval flow volume in newborn infants. METHODS: Echocardiographic and MRI assessments were performed within 1 working day of each other in a cohort of newborn infants. RESULTS: Examinations were performed in 49 infants with a median corrected gestational age at scan of 34.43 weeks (range, 27.43-40 weeks) and a median weight at scan of 1,880 g (range, 660-3,760 g). Echocardiographic assessment of left ventricular output showed a strong correlation with MRI assessment (R(2) = 0.83; mean bias, -9.6 mL/kg/min; limits of agreement, -79.6 to +60.0 mL/kg/min; repeatability index, 28.2%). Echocardiographic assessment of superior vena caval flow showed a poor correlation with MRI assessment (R(2) = 0.22; mean bias, -13.7 mL/kg/min; limits of agreement, -89.1 to +61.7 mL/kg/min; repeatability index, 68.0%). Calculating superior vena caval flow volume from an axial area measurement and applying a 50% reduction to stroke distance to compensate for overestimation gave a slightly improved correlation with MRI (R(2) = 0.29; mean bias, 2.6 mL/kg/min; limits of agreement, -53.4 to +58.6 mL/kg/min; repeatability index, 54.5%). CONCLUSIONS: Echocardiographic assessment of left ventricular output appears relatively robust in newborn infant. Echocardiographic assessment of superior vena caval flow is of limited accuracy in this population, casting doubt on the utility of the measurement for diagnostic decision making.

Development of cortical microstructure in the preterm human brain.

Cortical maturation was studied in 65 infants between 27 and 46 wk postconception using structural and diffusion magnetic resonance imaging. Alterations in neural structure and complexity were inferred from changes in mean diffusivity and fractional anisotropy, analyzed by sampling regions of interest and also by a unique whole-cortex mapping approach. Mean diffusivity was higher in gyri than sulci and in frontal compared with occipital lobes, decreasing consistently throughout the study period. Fractional anisotropy declined until 38 wk, with initial values and rates of change higher in gyri, frontal and temporal poles, and parietal cortex; and lower in sulcal, perirolandic, and medial occipital cortex. Neuroanatomical studies and experimental diffusion-anatomic correlations strongly suggested the interpretation that cellular and synaptic complexity and density increased steadily throughout the period, whereas elongation and branching of dendrites orthogonal to cortical columns was later and faster in higher-order association cortex, proceeding rapidly before becoming undetectable after 38 wk. The rate of microstructural maturation correlated locally with cortical growth, and predicted higher neurodevelopmental test scores at 2 y of age. Cortical microstructural development was reduced in a dose-dependent fashion by longer premature exposure to the extrauterine environment, and preterm infants at term-corrected age possessed less mature cortex than term-born infants. The results are compatible with predictions of the tension theory of cortical growth and show that rapidly developing cortical microstructure is vulnerable to the effects of premature birth, suggesting a mechanism for the adverse effects of preterm delivery on cognitive function.

Body fat is associated with reduced aortic stiffness until middle age.

Obesity is a major risk factor for cardiometabolic disease, but the effect of body composition on vascular aging and arterial stiffness remains uncertain. We investigated relationships among body composition, blood pressure, age, and aortic pulse wave velocity in healthy individuals. Pulse wave velocity in the thoracic aorta, an indicator of central arterial stiffness, was measured in 221 volunteers (range, 18-72 years; mean, 40.3±13 years) who had no history of cardiovascular disease using cardiovascular MRI. In univariate analyses, age (r=0.78; P<0.001) and blood pressure (r=0.41; P<0.001) showed a strong positive association with pulse wave velocity. In multivariate analysis, after adjustment for age, sex, and mean arterial blood pressure, elevated body fat% was associated with reduced aortic stiffness until the age of 50 years, thereafter adiposity had an increasingly positive association with aortic stiffness (ß=0.16; P<0.001). Body fat% was positively associated with cardiac output when age, sex, height, and absolute lean mass were adjusted for (ß=0.23; P=0.002). These findings suggest that the cardiovascular system of young adults may be capable of adapting to the state of obesity and that an adverse association between body fat and aortic stiffness is only apparent in later life.

Assessment of PDA shunt and systemic blood flow in newborns using cardiac MRI.

Patent ductus arteriosus (PDA) remains common in preterm newborns, but uncertainty over optimal management is perpetuated by clinicians' inability to quantify its true haemodynamic impact. Our aim was to develop a technique to quantify ductal shunt volume and the effect of PDA on systemic blood flow volume in neonates. Phase contrast MRI sequences were optimized to quantify left ventricular output (LVO) and blood flow in the distal superior vena cava (SVC) (below the azygos vein insertion), descending aorta (DAo) and azygos vein. Total systemic flow was measured as SVC + DAo-azygos flow. Echo measures were included and correlated to shunt volumes. 75 infants with median (range) corrected gestation 33(+6) (26(+4) -38(+6) ) weeks were assessed. PDA was present in 15. In 60 infants without PDA, LVO matched total systemic flow (mean difference 2.06 ml/kg/min, repeatability index 13.2%). In PDA infants, ductal shunt volume was 7.9-74.2% of LVO. Multiple linear regression analysis correcting for gestational age showed that there was a significant association between ductal shunt volume and decreased upper and lower body flow (p = 0.01 and p < 0.001). However, upper body blood flow volumes were within the control group 95% confidence limits in all 15 infants with PDA, and lower body flow volumes within the control group limits in 12 infants with PDA. Echocardiographic assessment of reversed diastolic flow in the descending aorta had the strongest correlation with ductal shunt volume. We have demonstrated that quantification of shunt volume is feasible in neonates. In the presence of high volume ductal shunting the upper and lower body flow volume are somewhat reduced, but levels remain within or close to the normal range for preterm infants.

Neonatal cardiac MRI using prolonged balanced SSFP imaging at 3T with active frequency stabilization.

UNLABELLED: Cardiac MRI in neonates holds promise as a tool that can provide detailed functional information in this vulnerable group. However, their small size, rapid heart rate, and inability to breath-hold, pose particular challenges that require prolonged high-contrast and high-SNR methods. Balanced-steady state free precession (SSFP) offers high SNR efficiency and excellent contrast, but is vulnerable to off-resonance effects that cause banding artifacts. This is particularly problematic in the blood-pool, where off-resonance flow artifacts severely degrade image quality. METHODS: In this article, we explore active frequency stabilization, combined with image-based shimming, to achieve prolonged SSFP imaging free of banding artifacts. The method was tested using 2D multislice SSFP cine acquisitions on 18 preterm infants, and the functional measures derived were validated against phase-contrast flow assessment. RESULTS: Significant drifts in the resonant frequency (165 ± 23Hz) were observed during 10-min SSFP examinations. However, full short-axis stacks free of banding artifacts were achieved in 16 subjects with stabilization; the cardiac output obtained revealed a mean difference of 9.0 ± 8.5% compared to phase-contrast flow measurements. CONCLUSION: Active frequency stabilization has enabled the use of prolonged SSFP acquisitions for neonatal cardiac imaging at 3T. The findings presented could have broader implications for other applications using prolong SSFP acquisitions.

Salvage assessment with cardiac MRI following acute myocardial infarction underestimates potential for recovery of systolic strain.

OBJECTIVES: Our aim was to evaluate the relationship between the degree of salvage following acute ST elevation myocardial infarction (STEMI) and subsequent reversible contractile dysfunction using cardiac magnetic resonance (CMR) imaging. METHODS: Thirty-four patients underwent CMR examination 1-7 days after primary percutaneous coronary intervention (PPCI) for acute STEMI with follow-up at 1 year. The ischaemic area-at-risk (AAR) was assessed with T2-weighted imaging and myocardial necrosis with late gadolinium enhancement. Myocardial strain was quantified with complementary spatial modulation of magnetisation (CSPAMM) tagging. RESULTS: Ischaemic segments with poor (<25 %) or intermediate (26-50 %) salvage index were associated with worse Eulerian circumferential (Ecc) strain immediately post-PPCI (-9.1 % ± 0.6, P = 0.033 and -11.8 % ± 1.3, P = 0.003, respectively) than those with a high (51-100 %) salvage index (-14.4 % ± 1.3). Mean strain in ischaemic myocardium improved between baseline and follow-up (-10.1 % ± 0.5 vs. -16.2 % ± 0.5 %, P < 0.0001). Segments with poor salvage also showed an improvement in strain by 1 year (-9.1 % ± 0.6 vs. -15.3 % ± 0.6, P = 0.033) although they remained the most functionally impaired. CONCLUSIONS: Partial recovery of peak systolic strain following PPCI is observed even when apparent salvage is less than 25 %. Late gadolinium enhancement (LGE) may not equate to irreversibly injured myocardium and salvage assessment performed within the first week of revascularisation may underestimate the potential for functional recovery. KEY POINTS: • MRI can measure how much myocardium is damaged after a heart attack. • Heart muscle that appears initially non-viable may sometimes partially recover. • Enhancement around the edges of infarcts may resolve over time. • Evaluating new cardio-protective treatments with MRI requires appreciation of its limitations.

Remodeling after acute myocardial infarction: mapping ventricular dilatation using three dimensional CMR image registration.

BACKGROUND: Progressive heart failure due to remodeling is a major cause of morbidity and mortality following myocardial infarction. Conventional clinical imaging measures global volume changes, and currently there is no means of assessing regional myocardial dilatation in relation to ischemic burden. Here we use 3D co-registration of Cardiovascular Magnetic Resonance (CMR) images to assess the long-term effects of ischemia-reperfusion injury on left ventricular structure after acute ST-elevation myocardial infarction (STEMI). METHODS: Forty six patients (age range 33-77 years) underwent CMR imaging within 7 days following primary percutaneous coronary intervention (PPCI) for acute STEMI with follow-up at one year. Functional cine imaging and Late Gadolinium Enhancement (LGE) were segmented and co-registered. Local left ventricular wall dilatation was assessed by using intensity-based similarities to track the structural changes in the heart between baseline and follow-up. Results are expressed as means, standard errors and 95% confidence interval (CI) of the difference. RESULTS: Local left ventricular remodeling within infarcted myocardium was greater than in non-infarcted myocardium (1.6%±1.0 vs 0.3%±0.9, 95% CI: -2.4% - -0.2%, P=0.02). One-way ANOVA revealed that transmural infarct thickness had a significant effect on the degree of local remodeling at one year (P<0.0001) with greatest wall dilatation observed when infarct transmurality exceeded 50%. Infarct remodeling was more severe when microvascular obstruction (MVO) was present (3.8%±1.3 vs -1.6%±1.4, 95% CI: -9.1% - -1.5%, P=0.007) and when end-diastolic volume had increased by >20% (4.8%±1.4 vs -0.15%±1.2, 95% CI: -8.9% - -0.9%, P=0.017). CONCLUSIONS: The severity of ischemic injury has a significant effect on local ventricular wall remodeling with only modest dilatation observed within non-ischemic myocardium. Limitation of chronic remodeling may therefore depend on therapies directed at modulating ischemia-reperfusion injury. CMR co-registration has potential for assessing dynamic changes in ventricular structure in relation to therapeutic interventions.