Search

Background: Biological heart age estimation can provide insights into cardiac aging. However, existing studies do not consider differential aging across cardiac regions. Purpose: To estimate biological age of the left ventricle (LV), right ventricle (RV), myocardium, left atrium, and right atrium using magnetic resonance imaging radiomics phenotypes and to investigate determinants of aging by cardiac region. Study type: Cross‐sectional. Population: A total of 18,117 healthy UK Biobank participants including 8338 men (mean age = 64.2 ± 7.5) and 9779 women (mean age = 63.0 ± 7.4). Field Strength/Sequence: A 1.5 T/balanced steady‐state free precession. Assessment: An automated algorithm was used to segment the five cardiac regions, from which radiomic features were extracted. Bayesian ridge regression was used to estimate biological age of each cardiac region with radiomics features as predictors and chronological age as the output. The "age gap" was the difference between biological and chronological age. Linear regression was used to calculate associations of age gap from each cardiac region with socioeconomic, lifestyle, body composition, blood pressure and arterial stiffness, blood biomarkers, mental well‐being, multiorgan health, and sex hormone exposures (n = 49). Statistical Test: Multiple testing correction with false discovery method (threshold = 5%). Results: The largest model error was with RV and the smallest with LV age (mean absolute error in men: 5.26 vs. 4.96 years). There were 172 statistically significant age gap associations. Greater visceral adiposity was the strongest correlate of larger age gaps, for example, myocardial age gap in women (Beta = 0.85, P = 1.69 × 10−26). Poor mental health associated with large age gaps, for example, "disinterested" episodes and myocardial age gap in men (Beta = 0.25, P = 0.001), as did a history of dental problems (eg LV in men Beta = 0.19, P = 0.02). Higher bone mineral density was the strongest associate of smaller age gaps, for example, myocardial age gap in men (Beta = −1.52, P = 7.44 × 10−6). Data Conclusion: This work demonstrates image‐based heart age estimation as a novel method for understanding cardiac aging. Evidence Level: 1. Technical Efficacy: Stage 1. [ABSTRACT FROM AUTHOR]

Purpose: Acetylcarnitine can be assessed in vivo using proton MRS (1H‐MRS) with long TEs and this has been previously applied successfully in muscle. The aim of this study was to evaluate a 1H‐MRS technique for liver acetylcarnitine quantification in healthy humans before and after l‐carnitine supplementation. Method: Baseline acetylcarnitine levels were quantified using a STEAM sequence with prolonged TE in 15 healthy adults. Using STEAM with four different TEs was evaluated in phantoms. To assess reproducibility of the measurements, five of the participants had repeated 1H‐MRS without receiving l‐carnitine supplementation. To determine if liver acetylcarnitine could be changed after l‐carnitine supplementation, acetylcarnitine was quantified 2 h after intravenous l‐carnitine supplementation (50 mg/kg body weight) in the other 10 participants. Hepatic lipids were also quantified from the 1H‐MRS spectra. Results: There was good separation between the acetylcarnitine and fat in the phantoms using TE = 100 ms. Hepatic acetylcarnitine levels were reproducible (coefficient of reproducibility = 0.049%) and there was a significant (p < 0.001) increase in the relative abundance after a single supplementation of l‐carnitine. Hepatic allylic, methyl, and methylene peaks were not altered by l‐carnitine supplementation in healthy volunteers. Conclusion: Our results demonstrate that our 1H‐MRS technique could be used to measure acetylcarnitine in the liver and detect changes following intravenous supplementation in healthy adults despite the presence of lipids. Our techniques should be explored further in the study of fatty liver disease, where acetylcarnitine is suggested to be altered due to hepatic inflexibilities. [ABSTRACT FROM AUTHOR]

Aims: Low levels of homoarginine and creatine are associated with heart failure severity in humans, but it is unclear to what extent they contribute to pathophysiology. Both are synthesized via L‐arginine:glycine amidinotransferase (AGAT), such that AGAT−/− mice have a combined creatine and homoarginine deficiency. We hypothesized that this would be detrimental in the setting of chronic heart failure. Methods and results: Study 1: homoarginine deficiency—female AGAT−/− and wild‐type mice were given creatine‐supplemented diet so that both had normal myocardial creatine levels, but only AGAT−/− had low plasma homoarginine. Myocardial infarction (MI) was surgically induced and left ventricular (LV) structure and function assessed at 6–7 weeks by in vivo imaging and haemodynamics. Study 2: homoarginine and creatine‐deficiency—as before, but AGAT−/− mice were given creatine‐supplemented diet until 1 week post‐MI, when 50% were changed to a creatine‐free diet. Both groups therefore had low homoarginine levels, but one group also developed lower myocardial creatine levels. In both studies, all groups had LV remodelling and dysfunction commensurate with the development of chronic heart failure, for example, LV dilatation and mean ejection fraction <20%. However, neither homoarginine deficiency alone or in combination with creatine deficiency had a significant effect on mortality, LV remodelling, or on any indices of contractile and lusitropic function. Conclusions: Low levels of homoarginine and creatine do not worsen chronic heart failure arguing against a major causative role in disease progression. This suggests that it is unnecessary to correct hArg deficiency in patients with heart failure, although supra‐physiological levels may still be beneficial. [ABSTRACT FROM AUTHOR]

Effects of continuous positive airway pressure (CPAP) on right ventricular (RV) function in patients with untreated mild‐to‐moderate obstructive sleep apnea (OSA) are unclear. In this exploratory analysis of cardiac magnetic resonance (CMR)‐derived indices of RV function in patients with minimally symptomatic OSA from the MOSAIC randomized control trial we found no effect of CPAP on RV CMR parameters. In those with lower RV ejection fraction and higher RV end‐ diastolic volume (EDV) at baseline, CPAP treatment appeared to improve RV function with a significant reduction in both RV EDV and RV end‐systolic volume although between‐group effects were not observed. These data suggest potential merit in a larger randomized study of CPAP in patients with mild‐to‐moderate OSA and a greater breadth of RV dysfunction. [ABSTRACT FROM AUTHOR]

Aims: Despite substantial improvements over the last three decades, heart failure (HF) remains associated with a poor prognosis. The sodium‐glucose co‐transporter‐2 inhibitor empagliflozin demonstrated significant reductions of HF hospitalization in patients with HF independent of the presence or absence of type 2 diabetes mellitus in the EMPEROR‐Reduced trial and cardiovascular mortality in the EMPA‐REG OUTCOME trial. To further elucidate the mechanisms behind these positive outcomes, this study aims to determine the effects of empagliflozin treatment on cardiac energy metabolism and physiology using magnetic resonance spectroscopy (MRS) and cardiovascular magnetic resonance (CMR). Methods and results: The EMPA‐VISION trial is a double‐blind, randomized, placebo‐controlled, mechanistic study. A maximum of 86 patients with HF with reduced ejection fraction (n = 43, Cohort A) or preserved ejection fraction (n = 43, Cohort B), with or without type 2 diabetes mellitus, will be enrolled. Participants will be randomized 1:1 to receive either 10 mg of empagliflozin or placebo for 12 weeks. Eligible patients will undergo cardiovascular magnetic resonance, resting and dobutamine stress MRS, echocardiograms, cardiopulmonary exercise tests, serum metabolomics, and quality of life questionnaires at baseline and after 12 weeks. The primary endpoint will be the change in resting phosphocreatine‐to‐adenosine triphosphate ratio, as measured by 31Phosphorus‐MRS. Conclusions: EMPA‐VISION is the first clinical trial assessing the effects of empagliflozin treatment on cardiac energy metabolism in human subjects in vivo. The results will shed light on the mechanistic action of empagliflozin in patients with HF and help to explain the results of the safety and efficacy outcome trials (EMPEROR‐Reduced and EMPEROR‐Preserved). [ABSTRACT FROM AUTHOR]

Purpose: Phosphorus spectroscopy (31P‐MRS) is a proven method to probe cardiac energetics. Studies typically report the phosphocreatine (PCr) to adenosine triphosphate (ATP) ratio. We focus on another 31P signal: inorganic phosphate (Pi), whose chemical shift allows computation of myocardial pH, with Pi/PCr providing additional insight into cardiac energetics. Pi is often obscured by signals from blood 2,3‐diphosphoglycerate (2,3‐DPG). We introduce a method to quantify Pi in 14 min without hindrance from 2,3‐DPG. Methods: Using a 31P stimulated echo acquisition mode (STEAM) sequence at 7 Tesla that inherently suppresses signal from 2,3‐DPG, the Pi peak was cleanly resolved. Resting state UTE‐chemical shift imaging (PCr/ATP) and STEAM 31P‐MRS (Pi/PCr, pH) were undertaken in 23 healthy controls; pH and Pi/PCr were subsequently recorded during dobutamine infusion. Results: We achieved a clean Pi signal both at rest and stress with good 2,3‐DPG suppression. Repeatability coefficient (8 subjects) for Pi/PCr was 0.036 and 0.12 for pH. We report myocardial Pi/PCr and pH at rest and during catecholamine stress in healthy controls. Pi/PCr was maintained during stress (0.098 ± 0.031 [rest] vs. 0.098 ± 0.031 [stress] P =.95); similarly, pH did not change (7.09 ± 0.07 [rest] vs. 7.08 ± 0.11 [stress] P =.81). Feasibility for patient studies was subsequently successfully demonstrated in a patient with cardiomyopathy. Conclusion: We introduced a method that can resolve Pi using 7 Tesla STEAM 31P‐MRS. We demonstrate the stability of Pi/PCr and myocardial pH in volunteers at rest and during catecholamine stress. This protocol is feasible in patients and potentially of use for studying pathological myocardial energetics. [ABSTRACT FROM AUTHOR]

Osteoporosis and ischemic heart disease (IHD) represent important public health problems. Existing research suggests an association between the two conditions beyond that attributable to shared risk factors, with a potentially causal relationship. In this study, we tested the association of bone speed of sound (SOS) from quantitative heel ultrasound with (i) measures of arterial compliance from cardiovascular magnetic resonance (aortic distensibility [AD]); (ii) finger photoplethysmography (arterial stiffness index [ASI]); and (iii) incident myocardial infarction and IHD mortality in the UK Biobank cohort. We considered the potential mediating effect of a range of blood biomarkers and cardiometabolic morbidities and evaluated differential relationships by sex, menopause status, smoking, diabetes, and obesity. Furthermore, we considered whether associations with arterial compliance explained association of SOS with ischemic cardiovascular outcomes. Higher SOS was associated with lower arterial compliance by both ASI and AD for both men and women. The relationship was most consistent with ASI, likely relating to larger sample size available for this variable (n = 159,542 versus n = 18,229). There was no clear evidence of differential relationship by menopause, smoking, diabetes, or body mass index (BMI). Blood biomarkers appeared important in mediating the association for both men and women, but with different directions of effect and did not fully explain the observed effects. In fully adjusted models, higher SOS was associated with significantly lower IHD mortality in men, but less robustly in women. The association of SOS with ASI did not explain this observation. In conclusion, our findings support a positive association between bone and vascular health with consistent patterns of association in men and women. The underlying mechanisms are complex and appear to vary by sex. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

Background & Aims: Liver cT1, liver T1, transient elastography (TE) and blood‐based biomarkers have independently been shown to predict clinical outcomes but have not been directly compared in a single cohort of patients. Our aim was to compare these tests' prognostic value in a cohort of patients with compensated chronic liver disease. Methods: Patients with unselected compensated liver disease aetiologies had baseline assessments and were followed up for development of clinical outcomes, blinded to the imaging results. The prognostic value of non‐invasive liver tests at prespecified thresholds was assessed for a combined clinical endpoint comprising ascites, variceal bleeding, hepatic encephalopathy, hepatocellular carcinoma, liver transplantation and mortality. Results: One hundred and ninety‐seven patients (61% male) with median age of 54 years were followed up for 693 patient‐years (median (IQR) 43 (26‐58) months). The main diagnoses were NAFLD (41%), viral hepatitis (VH, 25%) and alcohol‐related liver disease (ArLD; 14%). During follow‐up 14 new clinical events, and 11 deaths occurred. Clinical outcomes were predicted by liver cT1 > 825ms with HR 9.9 (95% CI: 1.29‐76.4, P =.007), TE > 8kPa with HR 7.8 (95% CI: 0.97‐62.3, P =.02) and FIB‐4 > 1.45 with HR 4.09 (95% CI: 0.90‐18.4, P =.05). In analysis taking into account technical failure and unreliability, liver cT1 > 825 ms could predict clinical outcomes (P =.03), but TE > 8kPa could not (P =.4). Conclusions: We provide further evidence that liver cT1, TE and serum‐based biomarkers can predict clinical outcomes, but when taking into account technical failure/unreliability, TE cut‐offs perform worse than those of cT1 and blood biomarkers. [ABSTRACT FROM AUTHOR]

Background and Aim: Non‐alcoholic fatty liver disease (NAFLD) is rapidly becoming the leading indication for liver transplant and is associated with increased cardiovascular and liver mortality, yet there are no licensed therapies. Sodium‐glucose cotransporter 2 (SGLT2) inhibitors are widely used for their glucose‐lowering effects in patients with type 2 diabetes (T2D). Preclinical models have suggested a beneficial impact on NAFLD, but clinical data are limited, and there are currently no data on patients without T2D. We aimed to investigate the impact of SGLT2 inhibition on NAFLD in overweight, nondiabetic patients and establish the effect these agents may have on the processes that regulate hepatic steatosis in vivo. Methods: We conducted an open‐label, experimental medicine pilot study on insulin‐resistant overweight/obese individuals (n = 10) using gold‐standard noninvasive assessments of NAFLD phenotype, including magnetic resonance spectroscopy, two‐step hyperinsulinemic euglycemic clamps, and stable isotope tracers to assess lipid and glucose metabolism. Investigations were performed before and after a 12‐week treatment with the SGLT2 inhibitor, dapagliflozin. Results: Despite a body weight reduction of 4.4 kg, hepatic steatosis was unchanged following treatment. Hepatic glucose production increased, and there was impairment of glucose disposal during the low‐dose insulin infusion. Although circulating, nonesterified, fatty acid levels did not change, the ability of insulin to suppress lipolysis was reduced. Conclusions: SGLT2 inhibition for 12 weeks does not improve hepatic steatosis in patients without T2D. Additional studies in patients with established T2D or impairments of fasting or postprandial glucose homeostasis are needed to determine whether SGLT2 inhibition represents a viable therapeutic strategy for NAFLD. (ClinicalTrials.gov Number NCT02696941). [ABSTRACT FROM AUTHOR]

Abstract: Aims: Progressive left ventricular (LV) remodelling with cardiac myocyte hypertrophy, myocardial fibrosis, and endothelial dysfunction plays a key role in the onset and progression of heart failure with preserved ejection fraction. The Beta3‐LVH trial will test the hypothesis that the β3 adrenergic receptor agonist mirabegron will improve LV hypertrophy and diastolic function in patients with hypertensive structural heart disease at high risk for developing heart failure with preserved ejection fraction. Methods and results: Beta3‐LVH is a randomized, placebo‐controlled, double‐blind, two‐armed, multicentre, European, parallel group study. A total of 296 patients will be randomly assigned to receive either mirabegron 50 mg daily or placebo over 12 months. The main inclusion criterion is the presence of LV hypertrophy, that is, increased LV mass index (LVMi) or increased wall thickening by echocardiography. The co‐primary endpoints are a change in LVMi by cardiac magnetic resonance imaging and a change in LV diastolic function (assessed by the E/e′ ratio). Secondary endpoints include mirabegron's effects on cardiac fibrosis, left atrial volume index, maximal exercise capacity, and laboratory markers. Two substudies will evaluate mirabegron's effect on endothelial function by pulse amplitude tonometry and brown fat activity by positron emission tomography using 17F‐fluorodeoxyglucose. Morbidity and mortality as well as safety aspects will also be assessed. Conclusions: Beta3‐LVH is the first large‐scale clinical trial to evaluate the effects of mirabegron on LVMi and diastolic function in patients with LVH. Beta3‐LVH will provide important information about the clinical course of this condition and may have significant impact on treatment strategies and future trials in these patients. [ABSTRACT FROM AUTHOR]

Background and Aims: Elevated serum ferritin is common in NAFLD, and is associated with more advanced disease and increased mortality. Hyperferritinaemia in NAFLD is often attributed to inflammation, while in other conditions ferritin closely reflects body iron stores. The aim of this study was to clarify the underlying cause of hyperferritinaemia in NAFLD. Methods: Ferritin levels were examined with markers of iron status, inflammation and liver injury across the clinical spectrum of NAFLD using blood, tissue and magnetic resonance (MR) imaging. A separate larger group of NAFLD patients with hepatic iron staining and quantification were used for validation. Results: Serum ferritin correlated closely with the iron regulatory hormone hepcidin, and liver iron levels determined by MR. Furthermore, ferritin levels reflected lower serum adiponectin, a marker of insulin resistance, and liver fat, but not cytokine or CRP levels. Ferritin levels differed according to fibrosis stage, increasing from early to moderate disease, and declining in cirrhosis. A similar pattern was found in the validation cohort of NAFLD patients, where ferritin levels were highest in those with macrophage iron deposition. Multivariate analysis revealed liver iron and hepcidin levels as the major determinants of serum ferritin. Conclusions: While hyperferritinaemia is associated with markers of liver injury and insulin resistance, serum hepcidin and hepatic iron are the strongest predictors of ferritin levels. These findings highlight the role of disordered iron homeostasis in the pathogenesis of NAFLD, suggesting that therapies aimed at correcting iron metabolism may be beneficial. [ABSTRACT FROM AUTHOR]

Background & Aims The diagnosis of non-alcoholic steatohepatitis and fibrosis staging are central to non-alcoholic fatty liver disease assessment. We evaluated multiparametric magnetic resonance in the assessment of non-alcoholic steatohepatitis and fibrosis using histology as standard in non-alcoholic fatty liver disease. Methods Seventy-one patients with suspected non-alcoholic fatty liver disease were recruited within 1 month of liver biopsy. Magnetic resonance data were used to define the liver inflammation and fibrosis score ( LIF 0-4). Biopsies were assessed for steatosis, lobular inflammation, ballooning and fibrosis and classified as non-alcoholic steatohepatitis or simple steatosis, and mild or significant (Activity ≥2 and/or Fibrosis ≥2 as defined by the Fatty Liver Inhibition of Progression consortium) non-alcoholic fatty liver disease. Transient elastography was also performed. Results Magnetic resonance success rate was 95% vs 59% for transient elastography ( P<.0001). Fibrosis stage on biopsy correlated with liver inflammation and fibrosis ( rs=.51, P<.0001). The area under the receiver operating curve using liver inflammation and fibrosis for the diagnosis of cirrhosis was 0.85. Liver inflammation and fibrosis score for ballooning grades 0, 1 and 2 was 1.2, 2.7 and 3.5 respectively ( P<.05) with an area under the receiver operating characteristic curve of 0.83 for the diagnosis of ballooning. Patients with steatosis had lower liver inflammation and fibrosis (1.3) compared to patients with non-alcoholic steatohepatitis (3.0) ( P<.0001); area under the receiver operating characteristic curve for the diagnosis of non-alcoholic steatohepatitis was 0.80. Liver inflammation and fibrosis scores for patients with mild and significant non-alcoholic fatty liver disease were 1.2 and 2.9 respectively ( P<.0001). The area under the receiver operating characteristic curve of liver inflammation and fibrosis for the diagnosis of significant non-alcoholic fatty liver disease was 0.89. Conclusions Multiparametric magnetic resonance is a promising technique with good diagnostic accuracy for non-alcoholic fatty liver disease histological parameters, and can potentially identify patients with non-alcoholic steatohepatitis and cirrhosis. [ABSTRACT FROM AUTHOR]

Purpose We present a new Bloch-Siegert four Angle Saturation Transfer (BOAST) method for measuring the creatine kinase (CK) first-order effective rate constant kf in human myocardium at 7 tesla (T). BOAST combines a variant of the four-angle saturation transfer (FAST) method using amplitude-modulated radiofrequency pulses, phosphorus Bloch-Siegert [ABSTRACT FROM AUTHOR]

Purpose: To propose a simple multicompartment model of the liver and use Bloch-McConnell simulations to demonstrate the effects of iron and fibrosis on shortened-MOLLI (shMOLLI) T1 measurements. Liver T1 values have shown sensitivity to inflammation and fibrosis, but are also affected by hepatic iron content. Modified Look-Locker inversion recovery (MOLLI) T1 measurements are biased by the lower T2 associated with high iron.Materials and Methods: A tissue model was generated consisting of liver cells and extracellular fluid (ECF), with iron-dependent relaxation rates. Fibrosis was imitated by increasing the ECF proportion. Simulations of the shMOLLI sequence produced a look-up table (LUT) of shMOLLI-T1 for a given ECF fraction and iron content. The LUT was used to calculate ECF(shMOLLI-T1 ), assuming normal hepatic iron content (HIC), and ECF(shMOLLI- T1,T2*), accounting for HIC determined by T2*, for 77 patients and compared to fibrosis assessed by liver biopsy.Results: Simulations showed that increasing HIC decreases shMOLLI-T1 , with an increase in HIC from 1.0 to 2.5 mg/g at normal ECF fraction decreasing shMOLLI-T1 by 160 msec, while increasing ECF increased ShMOLLI-T1 , with an increase of 20% ECF at normal iron increasing shMOLLI-T1 by 200 msec. Calculated patient ECF(shMOLLI-T1 ) showed a strong dependence on Ishak score (3.3 ± 0.8 %ECF/Ishak stage) and 1/T2* (-0.23 ± 0.04 %ECF/Hz). However, when iron was accounted for to produce ECF(shMOLLI- T1,T2*), it was independent of HIC but retained sensitivity to Ishak score.Conclusion: Use of this multicompartment model of the liver with Bloch-McConnell simulation should enable compensation of iron effects when using shMOLLI-T1 to assess fibrosis.Level Of Evidence: 1 J. Magn. Reson. Imaging 2017;45:450-462. [ABSTRACT FROM AUTHOR]

Purpose The translation of sophisticated phosphorus MR spectroscopy (31P-MRS) protocols to 7 Tesla (T) is particularly challenged by the issue of radiofrequency (RF) heating. Legal limits on RF heating make it hard to reliably suppress signals from skeletal muscle that can contaminate human cardiac 31P spectra at 7T. We introduce the first surface-spoiling crusher coil for human cardiac 31P-MRS at 7T. Methods A planar crusher coil design was optimized with simulations and its performance was validated in phantoms. Crusher gradient pulses (100 μs) were then applied during human cardiac 31P-MRS at 7T. Results In a phantom, residual signals were 50 ± 10% with BISTRO (B1-insensitive train to obliterate signal), and 34 ± 8% with the crusher coil. In vivo, residual signals in skeletal muscle were 49 ± 4% using BISTRO, and 24 ± 5% using the crusher coil. Meanwhile, in the interventricular septum, spectral quality and metabolite quantification did not differ significantly between BISTRO (phosphocreatine/adenosine triphosphate [PCr/ATP] = 2.1 ± 0.4) and the crusher coil (PCr/ATP = 1.8 ± 0.4). However, the specific absorption rate (SAR) decreased from 96 ± 1% of the limit (BISTRO) to 16 ± 1% (crusher coil). Conclusion A crusher coil is an SAR-efficient alternative for selectively suppressing skeletal muscle during cardiac 31P-MRS at 7T. A crusher coil allows the use of sequence modules that would have been SAR-prohibitive, without compromising skeletal muscle suppression. Magn Reson Med 75:962-972, 2016. © 2015 The Authors. Magnetic Resonance in Medicine Published by Wiley Periodicals, Inc. on behalf of International Society of Medicine in Resonance. [ABSTRACT FROM AUTHOR]

Purpose To explore the use and reproducibility of magnetic resonance-derived myocardial T1 mapping in patients with iron overload. Materials and Methods The research received ethics committee approval and all patients provided written informed consent. This was a prospective study of 88 patients and 67 healthy volunteers. Thirty-five patients underwent repeat scanning for reproducibility. T1 mapping used the shortened modified Look-Locker inversion recovery sequence (ShMOLLI) with a second, confirmatory MOLLI sequence in the reproducibility group. T2* was performed using a commercially available sequence. The analysis of the T2* interstudy reproducibility data was performed by two different research groups using two different methods. Results Myocardial T1 was lower in patients than healthy volunteers (836 ± 138 msec vs. 968 ± 32 msec, P < 0.0001). Myocardial T1 correlated with T2* (R = 0.79, P < 0.0001). No patient with low T2* had normal T1, but 32% ( n = 28) of cases characterized by a normal T2* had low myocardial T1. Interstudy reproducibility of either T1 sequence was significantly better than T2*, with the results suggesting that the use of T1 in clinical trials could decrease potential sample sizes by 7-fold. Conclusion Myocardial T1 mapping is an alternative method for cardiac iron quantification. T1 mapping shows the potential for improved detection of mild iron loading. The superior reproducibility of T1 has potential implications for clinical trial design and therapeutic monitoring. J. Magn. Reson. Imaging 2015;41:1505-1511. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Purpose To investigate for the first time the feasibility of aortic four-dimensional (4D) flow at 7T, both contrast enhanced (CE) and non-CE. To quantify the signal-to-noise ratio (SNR) in aortic 4D flow as a function of field strength and CE with gadobenate dimeglumine (MultiHance). Methods Six healthy male volunteers were scanned at 1.5T, 3T, and 7T with both non-CE and CE acquisitions. Temporal SNR was calculated. Flip angle optimization for CE 4D flow was carried out using Bloch simulations that were validated against in vivo measurements. Results The 7T provided 2.2 times the SNR of 3T while 3T provided 1.7 times the SNR of 1.5T in non-CE acquisitions in the descending aorta. The SNR gains achieved by CE were 1.8-fold at 1.5T, 1.7-fold at 3T, and 1.4-fold at 7T, respectively. Conclusion The 7T provides a new tool to explore aortic 4D flow, yielding higher SNR that can be used to push the boundaries of acceleration and resolution. Field strength and contrast enhancement at all fields provide significant improvements in SNR. Magn Reson Med 73:1864-1871, 2015. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Purpose To investigate whether saturation using existing methods developed for 3T imaging is feasible for clinical perfusion imaging at 7T, and to propose a new design of saturation pulse train for first-pass myocardial perfusion imaging at 7T. Methods The new design of saturation pulse train consists of four hyperbolic-secant (HS8) radiofrequency pulses, whose peak amplitudes are optimized for a target range of static and transmit field variations and radiofrequency power deposition restrictions measured in the myocardium at 7T. The proposed method and existing methods were compared in simulation, phantom, and in vivo experiments. Results In healthy volunteer experiments without contrast agent, average saturation efficiency with the proposed method was 97.8%. This is superior to results from the three previously published methods at 86/95/90.8%. The first series of human first-pass myocardial perfusion images at 7T have been successfully acquired with the proposed method. Conclusion Existing saturation methods developed for 3T imaging are not optimal for perfusion imaging at 7T. The proposed new design of saturation pulse train can saturate effectively, and with this method first-pass myocardial perfusion imaging is feasible in humans at 7T. Magn Reson Med 73:1450-1456, 2015. © 2014 The Authors. Magnetic Resonance in Medicine Published by Wiley Periodicals, Inc. on behalf of International Society of Medicine in Resonance. [ABSTRACT FROM AUTHOR]

Purpose To describe the assessment of the spatiotemporal distribution of relative aortic pressure quantifying the magnitude of its three major components. Methods Nine healthy volunteers and three patients with aortic disease (bicuspid aortic valve, dissection, and Marfan syndrome) underwent 4D-flow CMR. Spatiotemporal pressure maps were computed from the CMR flow fields solving the pressure Poisson equation. The individual components of pressure were separated into time-varying inertial ('transient'), spatially varying inertial ('convective'), and viscous components. Results Relative aortic pressure is primarily caused by transient effects followed by the convective and small viscous contributions (64.5, 13.6, and 0.3 mmHg/m, respectively, in healthy subjects), although regional analysis revealed prevalent convective effects in specific contexts, e.g., Sinus of Valsalva and aortic arch at instants of peak velocity. Patients showed differences in peak transient values and duration, and localized abrupt convective changes explained by abnormalities in aortic geometry, including the presence of an aneurysm, a pseudo-coarctation, the inlet of a dissection, or by complex flow patterns. Conclusion The evaluation of the three components of relative pressure enables the quantification of mechanistic information for understanding and stratifying aortic disease, with potential future implications for guiding therapy. Magn Reson Med 72:1162-1169, 2014. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Purpose Phosphorus magnetic resonance spectroscopy (31P-MRS) affords unique insight into cardiac energetics but has a low intrinsic signal-to-noise ratio (SNR) in humans. Theory predicts an increased 31P-MRS SNR at 7T, offering exciting possibilities to better investigate cardiac metabolism. We therefore compare the performance of human cardiac 31P-MRS at 7T to 3T, and measure T1s for 31P metabolites at 7T. Methods Matched 31P-MRS data were acquired at 3T and 7T, on nine normal volunteers. A novel Look-Locker CSI acquisition and fitting approach was used to measure T1s on six normal volunteers. Results T1s in the heart at 7T were: phosphocreatine (PCr) 3.05 ± 0.41s, γ-ATP 1.82 ± 0.09s, α-ATP 1.39 ± 0.09s, β-ATP 1.02 ± 0.17s and 2,3-DPG (2,3-diphosphoglycerate) 3.05 ± 0.41s (N = 6). In the field comparison (N = 9), PCr SNR increased 2.8× at 7T relative to 3T, the Cramer-Ráo uncertainty (CRLB) in PCr concentration decreased 2.4×, the mean CRLB in PCr/ATP decreased 2.7× and the PCr/ATP SD decreased 2×. Conclusion Cardiac 31P-MRS at 7T has higher SNR and the spectra can be quantified more precisely than at 3T. Cardiac 31P T1s are shorter at 7T than at 3T. We predict that 7T will become the field strength of choice for cardiac 31P-MRS. Magn Reson Med 72:304-315, 2014. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

A novel method based on high-performance ion chromatography inductively coupled plasma mass spectrometry employing strong anion exchange chromatography with HNO3 gradient elution for simultaneous analysis of orthophosphate and myo-inositol hexakisphosphate (IP6) in soil solution and plant extracts is presented. As inductively coupled plasma mass spectrometry analysis of phosphorus at m/ z 31 is hampered by N-based interferences, 31P was measured as 31P16O+ at m/ z 47 employing dynamic reaction cell technique with O2 as reaction gas. Orthophosphate and IP6 were separated within a total chromatographic run-time of 12 min revealing a limit of detection of 0.3 μmol/L. The coefficients of determination obtained in a working range of 1-100 and 1-30 μmol/L were 0.9991 for orthophosphate and 0.9968 for IP6, respectively. The method was successfully applied to extracts from three different soils as well as root and shoot extracts of Brassica napus L. The precision of three independently prepared soil extracts was in the range of 4-10% relative standard deviation for PO43− and 3-8% relative standard deviation for IP6. Soil adsorption/desorption kinetics for IP6/orthophosphate were performed for investigating the sorption behavior of the two P species in the experimental soils. [ABSTRACT FROM AUTHOR]

At clinical MRI field strengths (1.5 and 3 T), quantitative maps of the longitudinal relaxation time T1 of the myocardium reveal diseased tissue without requiring contrast agents. Cardiac T1 maps can be measured by Look-Locker inversion recovery sequences such as ShMOLLI at 1.5 and 3 T. Cardiovascular MRI at a field strength of 7 T has recently become feasible, but doubts have remained as to whether magnetization inversion is possible in the heart due to subject heating and technical limitations. This work extends the repertoire of 7 T cardiovascular MRI by implementing an adiabatic inversion pulse optimized for use in the heart at 7 T. A 'ShMOLLI+IE' adaptation of the ShMOLLI pulse sequence has been introduced together with new postprocessing that accounts for the possibility of incomplete magnetization inversion. These methods were validated in phantoms and then used in a study of six healthy volunteers to determine the degree of magnetization inversion and the T1 of normal myocardium at 7 T within a 22-heartbeat breathhold. Using a scanner with 16 × 1 kW radiofrequency outputs, inversion efficiencies ranging from −0.79 to −0.83 (intrasegment means; perfect 180° would give −1) were attainable across the myocardium. The myocardial T1 was 1925 ± 48 ms (mean ± standard deviation). Magn Reson Med, 70:1038-1046, 2013. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Purpose Quantitative mapping of the native T1 of the heart using the modified look-locker inversion recovery (MOLLI) technique provides high quality diagnostic information without requiring contrast agents. Previous work has considered the effects of T2 relaxation on MOLLI T1 measurements, finding that the T1 measured by MOLLI is biased, and that Saturation-recovery single-Shot Acquisition generates a more precise T1. However, despite detailed experiments and simulation the exact relaxation times observed in vivo remain unexplained, but might be due to magnetization transfer (MT). Methods We used an MT simulation based on the Bloch-McConnell equations to evaluate the most common MOLLI and saturation-recovery single-shot acquisition sequence variants. Results For myocardial tissue we find that the T1 measured by saturation-recovery single-shot acquisition is insensitive to MT and T2, whereas MT reduces the T1 measured by MOLLI (>10%) in addition to the effects due to T2 relaxation. Conclusions The consequences of this T1 underestimation by MOLLI are relevant. Increases in the actual T1 and T2 and decreases in MT will all result in an increase in T1 measured by MOLLI. Myocardial infarction demonstrates increased native T1 and T2 and decreased MT, indicating that these biases enhance the sensitivity of MOLLI to detect this and possibly other cardiovascular disease states. Magn Reson Med 70:664-670, 2013. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Copyright of Experimental Physiology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Quantitative metabolic profiling is preceded by dedicated sample preparation protocols. These multistep procedures require detailed optimization and thorough validation. In this work, a uniformly 13 C-labeled ( U13 C) cell extract was used as a tool to evaluate the recoveries and repeatability precisions of the cell extraction and the extract treatment. A homogenous set of biological replicates ( n = 15 samples of Pichia pastoris) was prepared for these fundamental experiments. A range of less than 30 intracellular metabolites, comprising amino acids, nucleotides, and organic acids were measured both in monoisotopic 12 C and U13 C form by LC- MS/ MS employing triple quadrupole MS, reversed phase chromatography, and HILIC. Recoveries of the sample preparation procedure ranging from 60 to 100% and repeatability precisions below 10% were obtained for most of the investigated metabolites using internal standardization approaches. Uncertainty budget calculations revealed that for this complex quantification task, in the optimum case, total combined uncertainty of 12% could be achieved. The optimum case would be represented by metabolites, easy to extract from yeast with high and precise recovery. In other cases the total combined uncertainty was significantly higher. [ABSTRACT FROM AUTHOR]

Phase-contrast magnetic resonance imaging is a technique that allows for characterization of regional cardiac function and for measuring transmural myocardial velocities in human hearts with high temporal and spatial resolution. The application of this technique (also known as tissue phase mapping) to murine hearts has been very limited so far. The aim of our study was to implement and to optimize tissue phase mapping for a comprehensive assessment of murine transmural wall motion. Baseline values for regional motion patterns in mouse hearts, based on the clinically used American Heart Association's 17-segment model, were established, and a detailed motion analysis of mouse heart for the entire cardiac cycle (including epicardial and endocardial motion patterns) is provided. Black-blood contrast was found to be essential to obtain reproducible velocity encoding. Tissue phase mapping of the mouse heart permits the detailed assessment of regional myocardial velocities. While a proof-of-principle application in a murine ischemia-reperfusion model was performed, future studies are warranted to assess its potential for the investigation of systolic and diastolic functions in genetically and surgically manipulated mouse models of human heart disease. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Purpose: To combine global cardiac function imaging with compressed sensing (CS) in order to reduce scan time and to validate this technique in normal mouse hearts and in a murine model of chronic myocardial infarction. Materials and Methods: To determine the maximally achievable acceleration factor, fully acquired cine data, obtained in sham and chronically infarcted (MI) mouse hearts were 2-4-fold undersampled retrospectively, followed by CS reconstruction and blinded image segmentation. Subsequently, dedicated CS sampling schemes were implemented at a preclinical 9.4 T magnetic resonance imaging (MRI) system, and 2- and 3-fold undersampled cine data were acquired in normal mouse hearts with high temporal and spatial resolution. Results: The retrospective analysis demonstrated that an undersampling factor of three is feasible without impairing accuracy of cardiac functional parameters. Dedicated CS sampling schemes applied prospectively to normal mouse hearts yielded comparable left-ventricular functional parameters, and intra- and interobserver variability between fully and 3-fold undersampled data. Conclusion: This study introduces and validates an alternative means to speed up experimental cine-MRI without the need for expensive hardware. J. Magn. Reson. Imaging 2011. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Hypoxia causes left ventricular dysfunction in the human heart, but the biochemical mechanism is poorly understood. Here, we tested whether short-term normobaric hypoxia leads to changes in cardiac energetics and early cardiac dysfunction. Healthy male volunteers (m=12, age 24±2 yr) were exposed to normobaric hypoxia in a purpose-built hypoxic chamber. The partial pressure of oxygen during end-tidal expiration (PETo2) was kept between 50 and 60 mmHg, and peripheral oxygen saturation (SaO2) was kept above 80%. Cardiac morphology and function were assessed using magnetic resonance imaging and echocardiography, both before and after 20 h of hypoxic exposure, and high-energy phosphate metabolism [measured as the phosphocreatine (PCr)/ATP ratio] was measured using 31P magnetic resonance spectroscopy. During hypoxia, PETO2 and SaO2 averaged 55 ± 1 mmHg and 83.6 ± 0.4%, respectively. Hypoxia caused a 15% reduction in cardiac PCr/ATP (from 2.0±0.1 to 1.7±0.1, P<0.01) and reduced diastolic function (measured as E/E', rising from 6.1 ±0.4 to 7.5±0.7, P<0.01). Normobaric hypoxia causes a rapid decrease in high-energy phosphate metabolism in the human cardiac left ventricle, which may lead to a decline in diastolic function. These findings are important in understanding the response of normal individuals to environmental hypoxia, and to situations in which disease reduces cardiac oxygen delivery. [ABSTRACT FROM AUTHOR]

A rapid, proton magnetic resonance spectroscopy method to evaluate human myocardial lipid levels in a single breath-hold at 3 T using a commercial whole-body system is presented. During a 10 s breath-hold, water unsuppressed and suppressed spectra were acquired by two phased array coils using a short-echo time spectroscopic stimulated echo (STEAM) sequence electrocardiogram-triggered to mid-diastole. Lipid-to-water ratios were obtained in the septum of 15 healthy volunteers, (0.46 ± 0.19)%. These results agreed well with ratios obtained from averaged spectra acquired in seven multiple breath-holds, (0.45 ± 0.20)%, providing increased signal-to-noise ratio but requiring longer acquisition times. Excellent correlation was found between the two methods ( r = 0.94, P < 0.05). Reproducibility of 1H MRS for measuring myocardial lipid levels in a short breath-hold was acceptable in five repeated measurements within the same subject (coefficient of variation = 19%). Thus, single breath-hold proton spectroscopy allows reliable and quick quantification of myocardial lipids at 3 T. Magn Reson Med, 2011. © 2011 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Aims In vitro studies have shown impairment of energy metabolism in cardiac fibroblasts from Fabry patients. A recent in vivo study reported an association between cardiac energy metabolism and increased myocardial mass in Fabry patients. We therefore assessed possible disturbances of cardiac energy metabolism in Fabry patients by in vivo 31P-MR-spectroscopy. Additionally, the effect of enzyme replacement therapy (ERT) on cardiac energetics was tested. Methods and results Twenty-three patients (41 ± 9 years; 10 females) with genetically proven Fabry disease were examined with a 1.5 T Scanner, and compared with an age-matched healthy control group. Eight patients underwent ERT and had follow-up examinations after 3 and 14 months. The high-energy phosphate molecules phosphocreatine (PCr) and adenosine triphosphate (ATP) were quantified in localized 31P-spectra by SLOOP (spectral localization with optimum point spread function). Cine- and late gadolinium enhancement (LGE) studies were also performed. When compared with healthy controls, Fabry patients demonstrated reduced PCr- (6.1 ± 1.9 vs. 8.8 ± 2.6 mmol/kg; P = 0.003) and ATP concentrations (3.9 ± 1.5 vs. 4.6 ± 1.0 mmol/kg; P = 0.048). During ERT, PCr concentrations increased (7.1 ± 1.5 mmol/kg vs. 6.1 ± 1.9; P < 0.05) and left ventricular mass decreased (215 ± 55 vs. 185 ± 45 g; P = 0.012). Disturbances in cardiac energetics were not correlated to the presence or absence of cardiac fibrosis on LGE. Conclusion Cardiac energy metabolism is disturbed in Fabry disease; this may play an important role in the pathogenesis of Fabry cardiomyopathy. Enzyme replacement therapy ameliorates energetic depression. [ABSTRACT FROM PUBLISHER]

ABSTRACT We postulated that changes in cardiac high-energy phosphate metabolism may underlie the myocardial dysfunction caused by hypobaric hypoxia. Healthy volunteers (n=14) were studied immediately before, and within 4 d of return from, a 17-d trek to Mt. Everest Base Camp (5300 m). 31P magnetic resonance (MR) spectroscopy was used to measure cardiac phosphocreatine (PCr)/ATP, and MR imaging and echocardiography were used to assess cardiac volumes, mass, and function. Immediately after returning from Mt. Everest, total body weight had fallen by 3% (P<0.05), but left ventricular mass, adjusted for changes in body surface area, had disproportionately decreased by 11% (P<0.05). Alterations in diastolic function were also observed, with a reduction in peak left ventricular filling rates and mitral inflow E/A, by 17% (P<0.05) and 24% (P<0.01), respectively, with no change in hydration status. Compared with pretrek, cardiac PCr/ATP ratio had decreased by 18% (P<0.01). Whether the abnormalities were even greater at altitude is unknown, but all had returned to pretrek levels after 6 mo. The alterations in cardiac morphology, function, and energetics are similar to findings in patients with chronic hypoxia. Thus, a decrease in cardiac PCr/ATP may be a universal response to periods of sustained low oxygen availability, underlying hypoxia-induced cardiac dysfunction in healthy human heart and in patients with cardiopulmonary diseases. [ABSTRACT FROM AUTHOR]

MRI has become an important tool to noninvasively assess global and regional cardiac function, infarct size, or myocardial blood flow in surgically or genetically modified mouse models of human heart disease. Constraints on scan time due to sensitivity to general anesthesia in hemodynamically compromised mice frequently limit the number of parameters available in one imaging session. Parallel imaging techniques to reduce acquisition times require coil arrays, which are technically challenging to design at ultrahigh magnetic field strengths. This work validates the use of an eight-channel volume phased-array coil for cardiac MRI in mice at 9.4 T. Two- and three-dimensional sequences were combined with parallel imaging techniques and used to quantify global cardiac function, T1-relaxation times and infarct sizes. Furthermore, the rapid acquisition of functional cine-data allowed for the first time in mice measurement of left-ventricular peak filling and ejection rates under intravenous infusion of dobutamine. The results demonstrate that a threefold accelerated data acquisition is generally feasible without compromising the accuracy of the results. This strategy may eventually pave the way for routine, multiparametric phenotyping of mouse hearts in vivo within one imaging session of tolerable duration. Magn Reson Med, 2010. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Obesity is an escalating global health problem associated with both an increased risk of death and an increased risk of cardiovascular events. Our goal was to use magnetic resonance imaging (MRI) to determine the effect of obesity and weight loss, in the absence of the traditional cardiovascular risk factors, on aortic pulse wave velocity (PWV) a reliable, reproducible, and accurate clinical measure of aortic stiffness linked to increased mortality. Fifty obese (BMI 38.3 ± 6.8 kg/m2) and eighteen normal-weight controls (BMI 22.0 ± 1.7 kg/m2) with no identifiable cardiovascular risk factors underwent vascular MRI to assess PWV between the ascending aorta at the level of the pulmonary artery and the abdominal aorta (AA). Twenty-eight subjects underwent repeat imaging after a 1-year period of weight loss. Both groups were well matched for age, systolic blood pressure, fasting glucose, and total cholesterol. Obesity was associated with a 14% increase in PWV (P = 0.021), and with elevated C-reactive protein (CRP) (P < 0.01) and leptin levels (P < 0.001) factors known to cause increase arterial stiffness. Weight loss (average 50% excess weight) was associated with a 14% improvement in PWV (P = 0.03), and with reductions in serum leptin levels (P < 0.01). Obesity, in the absence of the traditional cardiovascular risk factors, is associated with increased aortic PWV, a noninvasive clinical measure of aortic stiffness independently predictive of cardiovascular mortality. Significant weight loss results in improvements in aortic PWV. This may provide a potential link between both obesity and increased mortality, and the reduction in mortality that occurs with weight loss. [ABSTRACT FROM AUTHOR]

Aims To measure the activity of the key phosphotransfer enzymes creatine kinase (CK), adenylate kinase (AK), and glycolytic enzymes in two common mouse models of chronic heart failure. Methods and results C57BL/6 mice were subjected to transverse aortic constriction (TAC), myocardial infarction induced by coronary artery ligation (CAL), or sham operation. Activities of phosphotransfer enzymes CK, AK, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), 3-phosphoglycerate kinase (PGK), and pyruvate kinase were assessed spectrophotometrically. Mice were characterized by echocardiography or magnetic resonance imaging 5- to 8-week post-surgery and selected for the presence of congestive heart failure. All mice had severe left ventricular hypertrophy, impaired systolic function and pulmonary congestion compared with sham controls. A significant decrease in myocardial CK and maximal CK reaction velocity was observed in both experimental models of heart failure. However, the activity of AK and its isoforms remained unchanged, despite a reduction in its protein expression. In contrast, the activities of glycolytic phosphotransfer mediators GAPDH and PGK were 19 and 12% higher in TAC, and 31 and 23% higher in CAL models, respectively. Conclusion Chronic heart failure in the mouse is characterized by impaired CK function, unaltered AK, and increased activity of glycolytic phosphotransfer enzymes. This pattern of altered phosphotransfer activity was observed independent of the heart failure aetiology. [ABSTRACT FROM AUTHOR]

The article discusses the design and characterization of an eight-channel volume receive-coil array for magnetic resonance imaging (MRI) of mice at 400 megahertz (MHz). The array and a volume-transmit coil was combined and integrated into a probe head. The observed coil noise domination and signal-to-noise ratio (SNR) performance are tackled. The array enabled 3-fold accelerated imaging of mouse kidneys in vivo and reduced scan time requirements.

Friedreich's ataxia (FRDA) has been associated with both cardiac hypertrophy and to a lesser degree dilated cardiomyopathy. We have conducted a cross sectional magnetic resonance imaging (MRI) study of 25 patients with clinically and genetically confirmed FRDA and 24 healthy controls to analyse how disease parameters influence cardiac features in FRDA. MR cine imaging in the long and short axis planes was performed alongside clinical assessments. LV mass was most pronounced in FRDA patients with a larger genetic mutation (GAA1 repeats >600), earlier age of onset (<16years) and a shorter disease duration (<15 years). LV mass decreased with longer disease duration (>15 years), and independent of GAA1 repeat size and age of onset, suggesting cardiac thinning occurred with prolonged disease. Heart function was lower in patients with larger GAA1 repeat number and longer disease duration. Consequently, cardiac hypertrophy was more marked in FRDA patients with a larger GAA1 repeat number and younger age of onset, while prolonged disease duration was associated with lower LV mass and decreased heart function. It is important not only to understand the biochemical basis for these cardiac changes but also allow for these changes when assessing the effect of treatment of FRDA patients. © 2010 Movement Disorder Society [ABSTRACT FROM AUTHOR]

Purpose To investigate the accuracy (vs. standard manual analysis) and precision (scan-rescan reproducibility) of three-dimensional guide-point modeling (GPM) for the assessment of left ventricular (LV) function in mice. Methods Six male wildtype C57/Bl6 mice (weight 26.2 ± 1.1 g) were scanned twice, 3 days apart. Each scan was performed twice, at 0.2 mm/pixel with one average and at 0.1 mm/pixel with two averages. The 24 studies were anonymized and analyzed in blinded fashion using GPM and standard manual slice summation. Results The average error between GPM and standard analysis was 2.3 ± 5.8 mg in mass, 1.7 ± 3.2 μL in end-diastolic volume, 2.3 ± 3.1 μL in end-systolic volume, −2.7 ± 4.3% in ejection fraction, −0.6 ± 3.3 μL in stroke volume, and −0.31 ± 1.56 ml · min−1 in cardiac output (mean difference ± SD of differences, n = 24). The average time taken was 8.0 ± 2.5 minutes for 3D GPM and 48.5 ± 8.9 minutes for standard analysis ( n = 24). Scan-rescan reproducibility results were similar to the standard analysis. No significant differences were found using linear mixed effects modeling in either accuracy or precision between scan resolutions or analysis method. Conclusion 3D GPM enables fast analysis of mouse LV function, with similar accuracy and reproducibility to standard analysis. An image resolution of 0.2 mm/pixel with one average is adequate for LV function studies. J. Magn. Reson. Imaging 2009. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

31P MRS was evaluated on normal volunteers at 1.5 and 3 T, and the signal-to-noise ratio (SNR) of the two field strengths was calculated. The in vivo spin-lattice, T1, relaxation times for PCr and γ-ATP, which are essential for correcting for the effects of radiofrequency saturation on the PCr/ATP ratio, were determined at 3 T. The T1 values for six volunteers were 3.8 ± 0.7 s for PCr (mean ± SD) and 2.4 ± 1.1 s for γ-ATP, which are similar to reported values at 1.5 T, allowing us to use protocols developed at 1.5 T at the new clinical field strength of 3 T. Direct comparison between 1.5 T and 3 T in the same 10 subjects, using coils of identical geometry and identical pulse sequences gave a mean SNR for PCr at 3 T which was 206 ± 94% of that at 1.5 T. The linewidth for PCr increased from 13 ± 6 Hz at 1.5 T to 22 ± 12 Hz at 3 T. The coefficient of variation in the measurement of PCr/ATP, based on the Cramer-Rao lower bounds, was reduced from 32 ± 25% at 1.5 T to 18 ± 13% at 3 T. Thus, 31P MRS at 3 T is greatly improved by the increase in SNR compared with acquisitions at 1.5 T because of the higher field strength. Copyright © 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

MRI can accurately and reproducibly assess cardiac function in rodents but requires relatively long imaging times. Therefore, parallel imaging techniques using a 4-element RF-coil array and MR sequences for cardiac MRI in rats were implemented at ultra-high magnetic fields (9.4 Tesla [T]). The hypothesis that these developments would result in a major reduction in imaging time without loss of accuracy was tested on female Wistar rats under isoflurane anesthesia. High-resolution, contiguous short-axis slices (thickness 1.5 mm) were acquired covering the entire heart. Two interleaved data sets (i) with the volume coil (eight averages) and (ii) with the four-element coil array (one average) were obtained. In addition, two-, three-, and fourfold accelerated data sets were generated through postprocessing of the coil array data, followed by a TGRAPPA reconstruction, resulting in five data sets per rat (in-plane voxel size 100 × 100 μm). Using a single blinded operator, excellent agreement was obtained between volume coil (acquisition time: 88 min) and the fourfold accelerated (<3 min) data sets (e.g., LV mass 436 ± 21 mg vs 433 ± 19 mg; ejection fraction 74 ± 5% vs 75 ± 4%). This finding demonstrates that it is possible to complete a rat cine-MRI study under 3 min with low variability and without losing temporal or spatial resolution, making high throughput screening programs feasible. Magn Reson Med 59:636-641, 2008. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Rapid and precise phenotyping analysis of large numbers of wild-type and mutant mouse embryos is essential for characterizing the genetic and epigenetic factors regulating embryogenesis. We present a novel methodology that permits precise high-throughput screening of the phenotype of embryos with both targeted and randomly generated mutations. To demonstrate the potential of this methodology we show embryo phenotyping results produced in a large-scale ENU-mutagenesis study. In essence this represents an analysis pipeline, which starts with simultaneous micro-magentic resonance imaging (µMRI) screening (voxel size: 25.4 × 25.4 × 24.4 µm) of 32 embryos in one run. Embryos with an indistinct phenotype are then cut into parts and suspect organs and structures are analysed with HREM (high-resolution episcopic microscopy). HREM is an imaging technique that employs ‘positive’ eosin staining and episcopic imaging for generating three-dimensional (3D) high-resolution (voxel size: 1.07 × 1.07 × 2 µm) digital data of near histological contrast and quality. The results show that our method guarantees the rapid availability of comprehensive phenotype information for high numbers of embryos in, if necessary, histological quality and detail. The combination of high-throughput µMRI with HREM provides an alternative screening pipeline with advantages over existing 3D phenotype screening methods as well as traditional histology. Thus, the µMRI-HREM phenotype analysis pipeline recommends itself as a routine tool for analysing the phenotype of transgenic and mutant embryos. [ABSTRACT FROM AUTHOR]

Purpose: To compare cardiac cine MR imaging using steady state free precession (SSFP) and fast low angle shot (FLASH) techniques at 1.5 and 3 T, and to establish their variabilities and reproducibilities for cardiac volume and mass determination in volunteers. To assess the feasibility of SSFP imaging in patients at 3 T and to determine comparability to volume data acquired at 1.5 T.Materials and Methods: Ten healthy volunteers underwent cardiac magnetic resonance imaging using SSFP and segmented gradient-echo FLASH, using both a 1.5 and a 3 T MR system on the same day. Ten patients with impaired left ventricular (LV) function were also studied at both field strengths with SSFP.Results: For both SSFP and FLASH, field strength had no effect on the quantification of LV and right ventricular (RV) volumes, mass, or function (P > or = 0.05 for field strength for all parameters). At both 1.5 and 3 T, SSFP yielded smaller LV mass (e.g., at 3 T 109 +/- 30 g vs. 142 +/- 37 g; P = 0.011) and larger LV volume (e.g., at 3 T end-diastolic volume 149 +/- 37 mL vs. 133 +/- 31 mL at 5 T; P = 0.041) measurements than FLASH. In patients with reduced LV function, all volume and mass measurements were again similar for SSFP sequences at 1.5 vs. 3 T. In volunteers and patients, measurement variabilities for LV parameters were small for both field strength and sequences, ranging between 3.7% and 10.7% for mass.Conclusion: Compared to 1.5 T, cardiac cine MR imaging at 3 T, using either FLASH or SSFP sequences, is feasible and highly reproducible. Field strength does not have an influence on quantification of cardiac volume or mass, but the systematic overestimation of LV mass and underestimation of LV volume by FLASH compared to SSFP is present at both 1.5 and 3 T. Normal values for cardiac volumes and mass established at 1.5 T can be applied to scans obtained at 3 T. [ABSTRACT FROM AUTHOR]

Purpose To study young adult elite athletes with age- and sex-matched sedentary controls to assess sex-specific differences for left ventricular (LV) and right ventricular (RV) volumes and mass as well as for LV contraction and relaxation. Materials and Methods A total of 23 male athletes (mean age 25 ± 4 years, training 22 ± 7 hours/week in rowing, swimming, or triathlon) and 20 female athletes (mean age 24 ± 4 years, training 19 ± 5 hours/week in rowing, swimming, or triathlon) and age- and sex-matched sedentary controls (21 male/17 female) underwent cardiovascular magnetic resonance (CMR) imaging (1.5 Tesla). Cardiac phase contrast imaging using a black-blood k-space segmented gradient echo sequence was used for analysis of cardiac contraction and relaxation and steady-state free-precession cine images were acquired for determination of cardiac volumes and mass. Results Male and female athletes showed similar increases in LV and RV volume and mass indices when compared to controls (ranging between 15% and 42%). No sex-specific differences in training effect on LV and RV volumes, mass indices, and ejection fractions, as well as LV to RV ratios of these volume and mass indices (parameters of balanced LV and RV dilatation and hypertrophy) were observed (all P for interaction >0.05). Similarly, no sex-specific differences in training effect on cardiac contraction and relaxation were found (all P for interaction >0.05). Conclusion Young adult elite athletes do not show sex-specific adaptive structural and functional changes to exercise training in accordance with the benign nature of the hypertrophy associated with athlete's heart. J. Magn. Reson. Imaging 2006. © 2006 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Abstract: Mutation of cytoskeletal protein genes results in abnormal protein function and causes cardiomyopathy. We hypothesised that cardiac levels of cytoskeletal proteins, such as dystrophin, desmin and muscle LIM protein (MLP), would be altered during remodelling caused by myocardial infarction (MI). We measured left-ventricular morphology, function and cytoskeletal protein levels 10 weeks after coronary artery ligation or sham operation in male Wistar rats. Two-dimensional echocardiography revealed significant impairment of systolic function and decreased ejection fraction in infarcted hearts compared with sham (47±5% versus 73±4%), commensurate with the development of heart failure. Western blotting was used to measure levels of β-myosin heavy chain (β-MyHC), a marker of hypertrophy, and levels of dystrophin, desmin, MLP, β-tubulin, utrophin and syncoilin, using GAPDH for normalization. Relative to shams, β-MyHC and MLP levels were increased 1.9-fold and 1.7-fold, respectively, in infarcted rat hearts, whereas the levels of other cytoskeletal proteins were unchanged. Both MLP and desmin protein levels correlated negatively with ejection fraction, with the strongest relation between MLP and ejection fraction (r =−0.95, n =13, p <0.0001). This work suggests that MLP may play an important compensatory role in cardiac remodelling following MI. [Copyright &y& Elsevier]