Multiple linear regression analyses were performed to investigate associations of socio-demographic correlates and transport- and recreation-related PA on the dependent variables of the environmental perception. In this case, levels of PA were significant predictors for eight of the 15 items concerning environmental perceptions. Thus, the present study introduces the idea that residents with higher levels of transport and recreational PA may perceive their environment in a more “PA-favourable” way than residents with lower levels.The association between physical activity (PA) and variables of the perceived environment mainly originate from cross-sectional studies that introduced the idea that the environment influences the PA level of residents. However, the direction of cause and effect has not been solved with finality. The aim of this study was to investigate whether residents’ perception of their proximate environment differs depending on their level of PA in transport and recreation. We conducted a cross-sectional survey with residents of six different parts of the city of Cologne, Germany. The sample of 470 adults  filled in the Global Physical Activity Questionnaire (GPAQ), as well as the European Environmental Questionnaire ALPHA. To distinguish between residents with “low” and “high” PA, we split the samples into two on the basis of the specific median in transport- and recreation-related PA. In the “high” Promoting physical activity (PA) has evolved into a major public health priority in many countries all over the world . There iTo date, however, most studies are based on cross-sectional findings, which indicate the statistical association between environmental factors and PA, but do not provide us with evidence of a causal relationship . Thus, mThe normal bases for these studies are population-based samples reporting on their own neighbourhoods and on their own PA levels. The underlying assumption has been that the perception of items in the neighbourhoods is independent of levels of the participants’ PA. If, on the other hand, levels of PA affect perceptions of neighbourhoods, then it is important to establish to what extent that is so.  etc. might be involved. So far, indications that levels of PA may affect perceptions have been presented in few studies examining changes in environmental perceptions over time ,8,9. In Although these study results do not allow us to draw a conclusion about the direction of cause and effect and why the environmental perception changed, they strengthen the view that the causal relationship of the perceived neighbourhood environment and PA has not been solved with finality. It has been argued that the perception of the environment can be influenced by the PA level and that it is possible that increased levels of PA might influence the participants’ perceptions of the environment. It might be expected that a higher exposure to the environment through increased PA will lead to a more informed perception of the environment. To our knowledge, no studies to date have investigated how the environmental perception is associated with levels of PA in transport and recreation, which would indeed be of interest and may further our understanding of the interaction of the perception of the neighbourhood environment and PA behaviour. This leads us to the question: do residents with a higher PA level in transport and recreation perceive their environment in a different way from residents living in the same neighbourhood but having a low PA level in transport and recreation? Thus, the aim of the present study is to analyse residents’ perception of the same proximate environment and how it may relate to their levels of PA in transport and recreation. 2. Six parts of the city satisfied these criteria. Statistical data for Cologne and the selected parts of the city are presented in We conducted a cross-sectional survey in different parts of the city of Cologne in Germany. Cologne is subdivided into nine city districts with all in all 85 parts see . ParticiIn total, we received 1482 filled-in questionnaires from 79 parts of the city ). From the six selected parts of the city, we received 562 filled-in questionnaires. We excluded respondents because of missing information on sex (n = 4) and age (n = 9). In addition, 60 participants were eliminated from the analyses according to the GPAQ scoring protocol  and 19 pi.e., walking and cycling to get to and from places) and recreational activities [We used the Global Physical Activity Questionnaire (GPAQ)  to assestivities . In the Weekly minutes of moderate and vigorous intensity activity were calculated separately by multiplying the number of days per week by the duration for an average day. Reported minutes per week in each category were multiplied by the metabolic equivalent (MET), which is generally used for expressing the intensity of PA independently of body weight. Four METs corresponded to the time spent in moderate intensity activities and eight METs to the time spent in vigorous intensity activities . As outcValidity and reliability have been assessed previously in nine different countries. Concurrent validity between the International Physical Activity Questionnaire (IPAQ), a previously validated and accepted measure of physical activity, and the GPAQ showed a moderate to strong positive relationship (range 0.45 to 0.65) and reliability was of moderate to substantial strength  . The assessment of the perceived environment was self-administered using the German version of the European Environmental Questionnaire, ALPHA. This questionnaire consisted of nine themes concerning the neighbourhood , walking or cycle infrastructure, maintenance of infrastructure, neighbourhood safety, pleasure and aesthetics of the neighbourhood, cycling and walking network , home environment, workplace or study environment ) with a total of 49 items that were summed into 15 theme scores and have been described elsewhere ,17. The -2. For further socio-demographic variables, education and income levels were included. The educational level was categorised into the following levels based on the German school system: no graduation, 10 years of education, 12 years of education, 13 years of education, university degree or higher. Monthly household net income was assessed in nine categories and summarised in three groups: <€1000, €1000–€2000 and >€2000. The demographic variables measured self-reported age, sex and the body mass index (BMI), calculated using self-reported body weight and body height according to the formula BMI = body weight (kg) × (body height (m))t-test in the overall sample , as well as for each part of the city . To describe the relationship between residents with low and high PA, we also calculated the ratio of the environmental perception following the formula: high PA/low PA or 4th quartile/1st quartile. All analyses were performed using IBM SPSS Statistics 22 and Microsoft Excel 2010 for Windows. Medians were calculated for transport- and recreation-related PA in the overall sample as well as in the six selected parts of the city. To distinguish between residents with low and high transport- and recreation-related PA in the different parts of the city, we split each subsample into two on the basis of the specific median in transport- and recreation-related PA. To avoid “in-between” city district variation  in the fMultiple linear regression analyses were performed to investigate associations of socio-demographic correlates and transport- and recreation-related PA with the dependent variables of the environment perception in the 15 themes for the overall sample and each city district separately. We chose the forced entry method and included the following socio-demographic variables: age (continuous variable), BMI (continuous variable), education (four categories) and income level (three categories) and included transport- and recreation-related PA as a continuous variable. To overcome the influence of different environments in the overall sample, we used, as the dependent variable, the relative environmental perception and, as independent variables, the relative PA values. Statistical significance was set at a level of 0.05.vs. 510 MET min per week, with an overall median ratio of high/low PA of 3.09. The corresponding ratios between the city districts range between 2.4 for Nippes and 7.02 for Ehrenfeld, showing a great difference between the median of the low PA and the high PA groups.The overall median in transport and recreation-related PA was 330 MET minutes per week with a range between 233 and 510 MET minutes per week for the selected city districts see . For theThe relative means and standard deviations, as well as the ratio between the relative environmental perception of residents with low PA and high PA in the overall sample, are presented in In the six different districts of the city there was the following distribution of the environmental perception ratio (significantly more “PA-friendly” districts/non-significant districts/significantly less “PA-friendly” districts): density score (2/3/1), distance score (2/4/0), availability of sidewalks (1/5/0), availability of bike lanes (3/3/0), availability of infrastructure (1/5/0), maintenance of infrastructure (1/5/0), total safety (1/4/1), safety, crime (1/4/1), safety, traffic (1/5/0), pleasure (0/5/1), aesthetics (0/5/1), network (3/3/0), connectivity (2/4/0), home environment (1/5/0) and work or study environment (3/3/0) see . 2 values of multiple regression analyses for all subjects, as well as separately for the different city districts. In the overall model, higher levels of transport and recreation-related PA predicted higher levels of perceptions of the following environmental variables: “distance”, “availability of sidewalks”, “availability of bicycle lanes”, “availability of infrastructure”, “network”, “connectivity”, “home environment” and “work/study environment”. For the themes of “density”, “availability of bike lanes”, “maintenance of infrastructure”, “total safety”, “safety, crime”, “safety, traffic” and “pleasure”, no distinct direction of perception concerning the PA-levels was documented. For the theme “aesthetics”, a negative association was noted, meaning that with higher PA levels, the environment is perceived as being less aesthetic. i.e., examining the association between transport- and recreation-related PA and the perception of the environment by residents in six different neighbourhoods. Previous studies investigating possible environmental correlates of PA have shown that particularly themes that contribute to the concept of walkability, including the three key elements of residential density, land use mix and street connectivity, as well as access to destinations, an activity-friendly transport environment and aesthetics, are all positively related to PA in the different domains ,5,6. As Most of the results obtained from the differences between the dichotomised PA groups are supported by the results of the multiple regression analyses controlling for socio-demographic correlates. These indicate that residents with high PA perceive their neighbourhood in what is often considered to be a more “PA-favourable” way with regard to the themes of “distance”, “availability of sidewalks”, “availability of bicycle lanes”, “availability of infrastructure”, “network”, “connectivity”, “home environment” and “work/study environment” compared to the residents with low PA in the similar neighbourhood. The majority of these themes are in accord with the above-mentioned usually stated PA-related environmental correlates . These results indicate that a higher PA in transport and recreation may lead to an altered perception of the neighbourhood. This is in line with the results of recent PA intervention studies investigating the effect of increasing PA on the perception of the environment without actually altering it ,9. ReasoThe present comparisons of perceptions of the environment by participants with the lowest 25% levels of PA with the corresponding highest 25% levels of PA yield the same principal results as those for the dichotomised samples, whereas the magnitude of the differences appears to increase. The sizes of these differences  can be useful for analytical purposes in future as well as previous studies on these matters. In our opinion, these magnitudes of perceived environmental differences must be exceeded if we are to be able to interpret them as reflecting true differences in environmental features between neighbourhood areas that represent inhabitants with low and high levels of PA. Our results also show, however, that these associations of PA were not evident in all neighbourhoods and not for all environmental themes. This may be due to the relatively small number of individuals surveyed in each city district. Another reason for this could be found in the ratios of high PA/low PA for the different city districts. Ehrenfeld, with the highest ratio of 7.02, which is mainly due to the very low median of the low PA group, also exhibits very large differences in the perceptions of the environment. This may indicate that the associations with PA occur with quite low PA levels or stand out more clearly with large differences in the levels of PA. 2, which is the least dense district compared to the other city districts (see  et al. concerning the inconsistencies in the theme of “density”, namely, that this environmental theme seems to be associated differently in the European context compared to the results from the United States and Australia [The reasons for the inconsistency of the PA association in the theme “density” in different city districts may be a result of a high heterogeneity of buildings in Cologne, where even in small parts of the city, blocks of flats and detached houses are close together. The city district Braunsfeld with 6383 inhabitants per kmicts see  also hasRegarding the opposite association of “availability of bike lanes” and “maintenance of infrastructure” in Neustadt-South compared to the positive association in the other city districts, an explanation may be found in the specific situation of Neustadt-South that was characterised by extensive construction work in the past few years due to the work on a new underground railway in this area which resulted in obstruction of or damage to many bike lanes. The same explanation can be applied to the single negative association within the environmental themes “aesthetics” and “pleasure” in this district, which is in contrast to other data ,23. In tWith respect to “perceived safety”, there are overall mixed findings in the literature concerning an association with PA ,22,24, wThe use of subsamples in six different small neighbourhoods where objective neighbourhood factors are similar was one of the strengths of the study with the aim of investigating differences in the perception of the environment by PA level. However, the sample sizes were small and objective measurement of the neighbourhood environment, e.g., GIS, would have strengthened the analyses and results. Furthermore, a location-specific PA questionnaire that distinguishes between PA within and outside the local neighbourhood and takes account of context-specific PA behaviour, such as recreation- and transport-related walking, e.g. the Neighbourhood Physical Activity Questionnaire , would hThe present cross-sectional study lends support to the idea that residents with higher levels of transport and recreation PA may perceive their environment in a more “PA-favourable” way than residents with low PA living in the same neighbourhood. This finding adds to the research on the association between PA and the environment and strengthens the argument that we need more studies of this kind, as well as longitudinal studies looking at the association between PA and environmental perceptions in order to define causality.


Image) in order to study the effect of pre-load reduction on the heart with MRI. This is a pilot study to establish our methodology.Our group studies circulatory causes of exercise limitation in congenital heart patients with dilated right ventricle, but normal resting left ventricular ejection fraction. Cardiac MRI is the gold standard non-invasive tool for measuring heart chamber volume and blood vessel flow. We designed an MRI-compatible lower body negative pressure (LBNP) device (We measured ventricular volumes from standard contiguous short axis stack of gated SSFP cines (slice thickness 8mm), and great vessel flows just above the sino-tubular junction from standard phase contrast flow imaging at rest and at different levels of lower body vacuum  in nine healthy volunteers. We compared measurements taken at rest and different levels of vacuum with students' paired t-test.We found that end-diastolic volume (EDV) and stroke volume (SV) progressively decreased with increasing lower body vacuum, in both ventricles. The difference between rest and -20mmHg LBNP were as follows: LVEDV 160.64+-28.18ml vs 145.02+-25.61ml (p<0.0005), LVSV 98.44+-15.88ml vs 84.9+-12.38ml (p<0.005), RVEDV 174.81+-46.01ml vs 154.1+-34.65ml (p<0.01), RVSV 100.11+-18.34ml vs 89.51+-17.62ml (p<0.1 ns).Peak flow rate (PFR) and stroke volume measured with flow imaging also decreased both in the ascending aorta and the main pulmonary artery (MPA). The difference between rest and -20mmHg LBNP were as follows: Aortic SV 88.11+-16.72ml vs 72.8+-13.85ml (p<0.001), Aortic PFR 441.5+-75.84ml/s vs 387.47+-56.01ml/s (p<0.002), MPA SV 105.25+-19.86ml vs 84.42+-20.7ml (p<0.00002), MPA PFR 442.48+-84.38ml/s vs 375.22+-6974ml/s (p<0.0002).Heart rate (HR) increased slightly from rest at -20mmHg LBNP: 63.58+-10.49bpm vs 69.43+-11.76bpm (p<0.01).Interestingly RVEDV, RVSV and MPA SV were already significantly reduced at -5mmHg LBNP ; and most of the other parameters changed significantly already at -10mmHg, which will be further disussed.Blood pressure did not change significantly, and our volunteers did not indicate any discomfort.Our pilot study shows that our MRI compatible LBNP device is safe, exerts adjustable and non-invasive pre-load reduction, and the physiological cardiac response to it is well detectable with cardiac MRI.Funded by the general research budget of our Institution.


However, its relation with cardiac function in patients on recovery from acute heart failure (HF) remains unclear. In this cross-sectional study, we sought to investigate the association between myocardial TG content measured on magnetic resonance spectroscopy  were measured on a 3.0 T MR scanner. Fatty acid (FA) and unsaturated fatty acid (UFA) content was normalized against water (W) using the LC-Model algorithm. The patient population was dichotomized according to the left ventricular ejection fraction .p = 0.02). The myocardial UFA/TG ratio was associated with LV mass  and modestly related to LV end-diastolic volume . We also identified negative correlations of the myocardial FA/TG ratio with both LV mass  and LVEDV .H-MRS data were available for 48 patients and 21 controls. Of the 48 patients, 25 had a LVEF <50 % , whereas the remaining 23 had a normal LVEF . Myocardial UFA/W ratio was found to differ significantly in patients with low LVEF, normal LVEF, and controls  contains supplementary material, which is available to authorized users. Heart failure (HF), a clinical syndrome in which the heart is unable to provide sufficient blood flow to meet metabolic requirements, is a major public health concern because of its high prevalence, poor prognosis, and significant healthcare costs . In TaiwAlthough a beating heart utilizes fatty acids as a primary source of energy , an incr1H-MRS) is increasingly being used as a non-invasive, non-radiation exposure technique for the clinical assessment of myocardial lipid content [1H-MRS, ultimately allowing the discrimination between fatty acids (FA) and unsaturated fatty acids (UFA) deposition in the myocardium. However, studies focusing on the clinical usefulness of 1H-MRS imaging for the metabolic evaluation of HF patients are particularly lacking. We therefore designed the current cross-sectional investigation to analyze the associations between myocardial TG content measured on 1H-MRS and left ventricular (LV) function assessed on cardiovascular magnetic resonance (CMR) in patients who were hospitalized with HF. We demonstrate that patients who were discharged after hospitalization for acute HF had increased myocardial UFA content, which was inversely related with LV ejection fraction (LVEF), LV mass and, to a lesser extent, LV end-diastolic volume (LVEDV).Proton magnetic resonance spectroscopy , and the study participants provided their written informed consent. The study was registered at ClinicalTrials.gov (Identifier: NCT02378402).1H-MRS measures within a single CMR session was assessed in the first 10 control subjects enrolled in the study. Clinical variables and serum lipid parameters  were collected within 1 month of CMR.This study was conducted at a tertiary referral hospital with a dedicated HF center. The inclusion criteria for patients were as follows: (1) having been discharged from the Keelung Chang Gung Memorial Hospital following hospitalization for acute HF in the 6–12 months preceding the study; (2) absence of known coronary artery disease involving the cardiac septum; (3) age between 20 and 70 years; (4) willingness to comply with the standard treatment and follow-up schedule proposed by the HF center; (5) willingness to provide written informed consent. Patients were excluded if they met one of the following criteria: (1) lack of compliance or inability to follow treatment or scheduled visits; (2) contraindications to CMR ; (3) pregnancy or breastfeeding; and (4) positive history of open cardiac surgery. A multidisciplinary team centrally reviewed medical records of eligible patients to ensure the enrollment quality. The day before their CMR, the study participants were requested to fast overnight . The patCMR was performed on a 3.0-Tesla Skyra scanner  operating on the VD13 platform, with an 18-channel phased-array receiver body coil. Short-axis (contiguous 8-mm-thick slices) and standard long-axis views  cine images were obtained using Steady-State Free Precession (SSFP) cine imaging with the following parameters: repetition time, 3.4 ms; echo time, 1.2 ms; matrix, 256 × 256; field of view, 34 to 40 cm.3 spectroscopic volume within the interventricular septum with the following parameters: nominal TR/TE, 550 ms/33 ms; 64 averages; window size, 1024 points; bandwidth, 2000 Hz. Cardiac gating was determined from the manufacturer’s vector ECG signal, with the first pulse of the PRESS localization sequence being around the end-systole phase (before the beginning of the cardiac motion) [1H-MRS the composition of a phantom consisting of both UFAs and saturated FAs. Clinical MRS measures were repeated in the first ten control subjects within a single CMR session, with spectra reacquired using the same localizations and settings.Short-axis and 4-chamber SSFP cine images were obtained to prescribe the locations of MRS voxels with saturation slabs across subcutaneous and pericardial fat. The B0 shimming parameters were optimized with a (breath-hold) rapid B0 mapping method. Localized 1D MRS with Point-Resolved SpectroScopy (PRESS) was performed by selecting a 2 × 2 × 1-cm motion) –17. The  motion) . MyocardLVEF was calculated from short-axis cine LV images with vendor-provided post-processing software  on a separate workstation. LV endocardial and epicardial borders were traced manually at end-diastole and end-systole on the short-axis cine images to determine the LVEF and end-diastolic LV mass for each slice, and the respective EDV, end-systolic volume (ESV) were obtained from the tracing. The LV global function index (LVGFI) was calculated using the following formula:1H-MRS spectra were analyzed using the LC Model software , which automatically calculates a weighted coherent average over the multiple channels and analyzes the resultant spectra  or one-way analysis of variance . Bivariate correlation analyses (Spearman’s rho) were performed to test the association between LV parameters and myocardial TG content. A value of p < 0.05 (two-sided) was considered statistically significant.The study variables were summarized using descriptive statistics. A Bland-Altman plot was used to assess the reproducibility between two-repeated he study . Continu1H-MRS data of 48 patients and 21 controls were included for analysis. Of the 48 patients, 25 had a low LVEF , whereas the remaining 23 had a normal LVEF . The distribution of the clinical characteristics of HF patients with low and normal LVEF was as follows: history of ischemic heart disease, 32 and 35 %, respectively; diabetes mellitus (DM), 58 and 74 %, respectively; dilated cardiomyopathy, 20 and 17 %, respectively; and myocarditis, 12 and 4 %, respectively. HF patients  did not differ significantly from controls in terms of age, sex, body weight, and body mass index . Serum HDL levels were significantly higher in HF patients with low LVEF (45.4 mg/dL) compared with the normal LVEF group .A total of 50 patients who were discharged after hospitalization for acute HF and 21 age- and sex-matched normal controls were included in the study. The flow chart of patient selection algorithm, and the numbers of participants recruited in each subgroup is summarized in Fig. The CMR data of the study participants are summarized in Table 1H-MRS was found to be an accurate and reliable technique to quantify and discriminate between unsaturated fatty acids and fatty acids in the phantom study , but no in terms of TG/W and FA/W content. Moreover, the myocardial UFA/W content was significantly higher in the low LVEF group compared with the normal LVEF group (p = 0.03). The myocardial UFA/TG ratio was strongly associated with LV mass  and modestly related to LVEDV . We also identified negative correlations of myocardial FA/TG ratio with both LV mass  and LVEDV  . The standard deviation of UFA/W was significantly larger in patients with low EF compared with values observed in patients with normal EF and controls  was 26.1 kg/mcriteria . Previoucriteria , 16, 17.criteria . Howeverr = 0.39 and 0.24, respectively) and large confidence intervals for the spectral quantification were evident. Therefore, caution should be exercised in the interpretation of our findings. Future larger studies will be needed to establish whether myocardial UFA content may vary between HF patients with different etiologies. Second, 1H-MRS measurements of myocardial TG content were not validated by histological examination of biopsies, mainly because of ethical concerns. Finally, it is unclear whether the accumulation of myocardial TG results from increased uptake of fatty acids, higher de novo lipogenesis, or reduced lipid degradation. Further studies are required to clarify the pathophysiological mechanisms of myocardial TG accumulation in HF patients.Several caveats of our study merit comment. First, our subgroup analysis is limited by the small sample size. Although myocardial UFA/TG was positively related with LV mass and LVEDV, these relationships were fairly weak (1H-MRS for predicting clinical outcomes.Patients who were discharged after hospitalization for acute HF had increased myocardial UFA content as compared with controls. Furthermore, UFA was inversely related with LVEF, LV mass and, to a lesser extent, LVEDV. Our current report may stimulate further research aimed at measuring myocardial UFA content by


Cardiac involvement with progressive myocardial fibrosis leading to dilated cardiomyopathy is a major cause of death in muscular dystrophy patients. Extracellular volume fraction (ECV) measurement based on T1-mapping pre- and post-contrast promises the detection of early "diffuse" myocardial fibrosis that cannot be depicted by conventional contrast-imaging based on late gadolinium enhancement (LGE). With this study, we evaluated the presence of diffuse myocardial fibrosis in regions of "normal" (LGE-negative) and "diseased" (LGE-positive) appearing myocardium as well as its relation to the extent of left ventricular (LV) dysfunction and the occurrence of arrhythmias in Becker muscular dystrophy (BMD) patients.Twenty-seven BMD patients (35 ± 12 yrs) and 28 matched healthy CONTROLS (33 ± 8 yrs) underwent cardiovascular magnetic resonance (CMR) studies including ECV measurement and LGE-imaging. Ambulatory monitoring of arrhythmic events was performed by means of an external event loop recorder.Twenty BMD patients (74%) demonstrated cardiac involvement as detected by typical inferolateral presence of LGE. Twelve patients (44%) had an impaired LV ejection fraction - all being LGE-positive. Global myocardial ECV was significantly higher in the BMD group (29 ± 6%) compared to the CONTROL group . Patients with cardiac involvement demonstrated higher global ECV (31 ± 6%) as well as significantly increased regional ECV not only in LGE-positive segments (34 ± 6%), but also in LGE-negative segments (28 ± 6%) compared to BMD patients without cardiac involvement and to CONTROLS, respectively . Global ECV in patients with cardiac involvement substantially correlated to LV ejection fraction  and to the number of LGE-positive segments . On univariable analysis, global ECV - but not the categorical presence of LGE per se - was significantly associated with arrhythmic events .ECV measurement by CMR is a useful tool in assessing the total extent of myocardial fibrosis as well as in depicting subtle diffuse fibrosis in areas of normal appearing myocardium on LGE-images. Thus, myocardial ECV is a potential additional quantitative tool for accurate detection of cardiac involvement and risk stratification in muscular dystrophy patients.This work was financially supported by a grant from the German Society of Cardiology  and by the Robert-Bosch-Foundation (grant-ID KKF-11-14 to A.Y.).


CMR quantification of LV chamber volumes typically and manually defines the basal-most LV, which adds processing time and user-dependence. This study developed an LV segmentation method that is fully automated based on the spatiotemporal continuity of the LV (LV-FAST). An iteratively decreasing threshold region growing approach was used first from the midventricle to the apex, until the LV area and shape discontinued, and then from midventricle to the base, until less than 50% of the myocardium circumference was observable. Region growth was constrained by LV spatiotemporal continuity to improve robustness of apical and basal segmentations. The LV-FAST method was compared with manual tracing on cardiac cine MRI data of 45 consecutive patients. Of the 45 patients, LV-FAST and manual selection identified the same apical slices at both ED and ES and the same basal slices at both ED and ES in 38, 38, 38, and 41 cases, respectively, and their measurements agreed within −1.6 ± 8.7 mL, −1.4 ± 7.8 mL, and 1.0 ± 5.8% for EDV, ESV, and EF, respectively. LV-FAST allowed LV volume-time course quantitatively measured within 3 seconds on a standard desktop computer, which is fast and accurate for processing the cine volumetric cardiac MRI data, and enables LV filling course quantification over the cardiac cycle. Quantifying left ventricular (LV) function is essential for diagnosing and planning therapy for cardiac diseases –3. ModalTraditional LV volume assessment has been limited to the examination of systolic performance using manual delineation of the LV endocardium at end systolic and end diastolic phases. It will take 5–10 minutes to manually delineate LV endocardium for a stack of about 20 images of the two phases . DiastolAmong existing automated methods , approacIn this work we propose an LV segmentation method that addresses these challenges in a manner that is fully automated, based on the spatiotemporal continuity (LV-FAST). Using the assumption that cardiac volumes are smoothly varying through space and time, we can constrain the segmentation in each slice at a cardiac phase using information from spatiotemporally neighboring segmentations. This spatiotemporal continuity can be used to transfer knowledge from segmentations in areas of the LV that are easy to segment, for guiding segmentation in more challenging areas, such as the basal and apical slices, where previous methods have not been reliable and manual tracing is necessary.IRB approval was obtained for retrospective image analysis on deidentified data. This study involved 30 deidentified subjects who underwent Cine CMR, whose data was used for initial algorithm development and empirical parameter selection  below. ACine CMR image data were acquired using a 2D SSFP pulse sequence on 1.5 T  scanners. In each subject, LV anatomy was imaged in 8–16 short axis slices from the level of the mitral valve annulus through the LV apex. Typical CMR imaging parameters were repetition time (TR) 3.5 ms, echo time (TE) 1.6 ms, flip angle 60°, matrix size 256 × 256, image dimensions 256 × 256, receiver bandwidth 125 kHz, FOV: 360 mm, slice thickness 6–8 mm, slice gap 2–4 mm (thickness + gap = 10 mm), and 20–28 reconstructed cardiac temporal phases.Cine CMR image postprocessing, including initial LV localization and segmentation  and phase 8  and then extracting the center point of the difference image using the Hough transform . By usinThis seed point is then propagated across all temporal phases for the slice and used to segment those images. After segmentation across all images in this slice position, the center of mass of the LV blood pool in a segmented slice was used as the seed point on an adjacent slice in the superior and/or inferior directions.A previously described iterative region growing method , which hx-, y-, and z-axes represent the slice, phase, and segmentation area, respectively, of the corresponding extracted region , the image was denoted as a “jump image,” and its corresponding phase and slice were denoted as a “jump phase” and “jump slice.” These jump images were close to the apex or base of the heart's LV region. Jump images denote where the algorithm of All short axis slices of the LV, except the most basal and apical segments, demonstrated volumetric spatiotemporal continuity: the LV volumes in these short axis slices were fairly smooth or changed slowly over the temporal cardiac phase and the slice location shown in . This coshown in . Each cic method . If J > (a) Apical Section Estimation. When a “jump image” was detected in the apical end of the cardiac volume, a nearby phase was used to estimate the segmentation. We denote the estimated apical segmented area of a slice at phase p and slice s by A′. This value was computed from the LV area of slice s at the nearest phase q without a detected jump , using a linear scaling factor that represents the scale difference in volume of that section of the heart between the two phases:s was large (at least 90%), the corresponding phases at slice s + 1 were segmented according to s + 1 at various phases were calculated using a cone interpolation. For any phase p, the apical area of slice s is related to that of its proceeding two adjacent slices s − 1 and s − 2 according to(b) Basal Section Segmentation. The jump parameters were used to locate basal slices. In accordance with previously established conventions, the most basal LV image has at least 50% of its LV circumference in contact with myocardium [D pixels. The two apparent myocardial termination angle lines were then searched from zero angles in the top to the 360° angle line in the bottom in D pixels compared to those in ocardium . The perThe main parameters mentioned in The LV-FAST algorithm was applied to cardiac short axis cine SSFP CMR images in order to obtain the following LV parameters: end diastolic volume (EDV), end systolic volume (ESV), ejection fraction (EF), volume filling curves, and the most basal and apical slices at each temporal phase. The LV-FAST derived parameters  were compared with the LV-METRIC algorithm  that wasP < 0.05) were calculated to compare the automated and manual results in this study. A linear regression was performed to assess correlations between the manual and fully automated measurements, and a Bland-Altman analysis was used to compare volume estimations between manual tracing and the automated methods.The mean and standard deviation of paired differences  and 91% (n = 41) of cases. For basal slice identification, the two approaches agreed 84%  cases for both ED and ES. For the 7 cases in which automated and manual results did not match for defining the most apical slice at ED, LV-FAST overestimated one slice in 4 cases and underestimated one slice in the remaining 3 cases. For all 4 discrepant cases in defining the most apical position at ES, LV-FAST overestimated one slice in all 4 cases. For the 7 discrepant cases in defining the most basal slice at ED, LV-FAST overestimated one slice in 3 cases and underestimated one slice in the remaining 4 cases. Finally in the 7 discrepant cases in defining the most basal slice at ES, LV-FAST overestimated one slice in 4 cases and overestimated two slices in the remaining 3 cases.Of the 45 consecutive cases, LV-FAST and manual segmentation agreed in over three-fourths of cases: The two approaches detected the identical apical slices at ED and ES phases in 84% (P = 0.41); mean volumes in ES were 60 ± 31 mL and 58 ± 33 mL, respectively (P = 0.29); EF were 61 ± 12% and 62 ± 13%, respectively (P = 0.25). Corresponding Bland-Altman plots for between automated LV-FAST and manual segmentation results are illustrated in LV volumes at ED, ES, and EF measured by the fully automated LV-FAST and manual segmentation are summarized in We proposed a fully automated method for quantifying the LV functional parameters using spatiotemporal continuity (LV-FAST), which can define the basal and apical slices at all cardiac phases and estimate corresponding LV volumes. Our experimental results on LV volume measurements showed that LV-FAST is in good agreement with the manual segmentation results by an experienced physician, suggesting that LV-FAST can be used for fast quantification of the LV stroke volumes, ejection fractions, and enabling filling curves on routine clinical CMR that is not possible with manual segmentation.Unlike prior automated algorithms , 25–30, J > 2.5, or D > 6 empirical values was based upon a learning algorithm generated from 30 CMR exams, which may not be suitable for all cases. In our 45 consecutively selected subjects, two subjects were found with large shifts between slices. This large slice misregistration might be caused by inconsistency in breath-holding or cardiac arrhythmia, both of which could be causal-FAST's misdetection of the basal slice. Estimation of myocardial circumference might be affected by the low image contrast and signal-to-noise ratio close to the most basal slice. Image quality improvement for Cine CMR such as 3D cine imaging [There are differences between LV-FAST and manual segmentation, as described in  imaging  under frIn summary, an algorithm for left ventricle segmentation with full automation using spatiotemporal continuity (LV-FAST) is presented for fast and accurate processing of the cine volumetric cardiac MRI data, enabling LV filling course quantification over the cardiac cycle.


We intended to establish the threshold of Anti-Mullerian Hormone (AMH) for detection of Ovarian Hyper-Stimulation Syndrome (OHSS) and poor response to treatment in Iranian infertile women.Pre-stimulation menstrual cycle day-3 hormonal indices including basal AMH values were measured in 105 infertile women aged 32.5 ± 4.3 years. Patients underwent long GnRH agonist Controlled Ovarian Hyperstimulation (COH) in a referral infertility center . The gonadotropin dose was determined based on the age and basal serum Follicular Stimulating Hormone (FSH) level. The IVF/ICSI cycles were followed and the clinical and sonographic data were recorded.Sixteen cases developed OHSS. The prevalence of PCOS was higher in subjects with OHSS [62.5 % (38.8-86.2) vs. 17 % (9.2-24.9)]. The patients with OHSS had higher ovarian follicular count , collected oocytes  and AMH level . Basal AMH level and oocyte yields  correlated with occurrence of OHSS; and only the AMH levels were associated with poor ovarian response (oocytes yield ≤ 4). The optimal cutoff value for the prediction of OHSS was 6.95 ng/ml . The optimal cut point to discriminate poor response (oocytes ≤4) was 1.65 ng/ml .Iranian women with basal AMH level > 6.95 ng/ml are at high risk of developing OHSS and those with AMH level < 1.65 ng/ml are poor responders. Sensitiicity)2] . A binarThe AMH values were not normally distributed  and were positively skewed. For the parametric tests the square root of the AMH values was generated and employed .The subjects’ characteristics are shown in Table Twenty-five subjects  had PCOS with higher prevalence of OHSS , younger age  and higher basal AMH levels . Their pregnancy rate, however, was not statistically different from other patients .The binary logistic regression model was designed with age, BMI, number of previous OSCs, PCOS, FSH level, number of retrieved oocytes, and basal AMH level (square root) as independent variables to predict the OHSS (dependent variable). The number of retrieved oocytes  and basal AMH value   were significant independent predicting factors of OHSS. The square root of basal AMH levels were moderately correlated with the number of retrieved oocytes . Another model was defined with follicle count instead of collected oocytes count (considering significant co-linearity). In this model, in addition to AMH level the follicle count was significantly associated with OHSS . A binary logistic regression model was defined with independent variables identical to those of the previous models excluding collected oocyte or follicle counts. AMH level (square root) was the only predictor of the response to stimulation .The total administered gonadotropin dose  correlated inversely with the OHSS occurrence .2 = 0.1; P = 0.001]. No significant interaction effect was detected for the presence of PCOS on the association of AMH levels and OHSS  with higher collected oocytes  and the equal follicle count . The cutoff value of AMH with the best prediction of poor response to controlled ovarian stimulation (oocytes ≤4) was 1.65 ng/ml with AUC of 0.8 (0.69-0.91) and sensitivity and specificity of 89 % and 71 %, respectively . The cut points for detection of OHSS and poor response were substantially the same after exclusion of subject with PCOS (data not shown).AMH levels classified subjects with and without OHSS with an area under the ROC curve (AUC) of 0.86 .Our results indicate an association between extreme AMH levels and OHSS and poor response to controlled ovarian stimulation independent of the effect of age, BMI, and a history of PCOS. According to our findings, subjects with an AMH level <1.65  are more likely to be poor responders to ovarian stimulation  and those with AMH levels >6.95  are at a higher risk for OHSS . With subclass analysis of the administered gonadotropin dose, we suggest that milder ovarian stimulation in high risk patients has no detrimental effect on the COH main outcome (retrieved oocyte count). Thus, we believe that based on the proposed cut point of basal AMH levels , reduced stimulation would be a safe and the reasonable method of preventing OHSS and its consequences. This approach may decrease the severe OHSS cases with its unfavorable consequences including hospitalization and cycle cancellation . After ath percentile) for the classification of exaggerated responses. The threshold value of the study by Lee et al. was numerically lower but again it was the 75th percentile of the AMH values of the studied population. Ebner et al. [th and 75th percentiles with reduced oocyte quality of patients in the top quartile (AMH level > 4.5 ng/ml). The cutoff point suggested by Nardo et al. (3.5 ng/ml) is presumably the upper quartile of non-PCOS normal responders to COH. The differences between the AMH thresholds for higher OHSS risk noted in this study as compared to other studies may be explained by the differences between the studied populations , the definition of OHSS, and the different AMH measurement methods. Roughly - also not limited by the remarkable difference between the AMH readings of two older ELISA kits i.e. DSL and Immunotech - the patients with upper quartile AMH values are at high risk for exaggerated ovarian response [Our optimal cutoff value of AMH for the prediction of OHSS is higher than the cut points suggested by previous studies  as compared with the results of Nardo et al. (24 %) , Kini etOur study suffers from certain flaws: above all the OHSS was mainly diagnosed based on the decision of the chief researcher who decided also for the future treatment of the patients. This reduces the extend the results could be extrapolated. The sample size of the study was also rather small, hence the conclusion regarding the pregnancy rate after assisted reproduction cycles should be interpreted with caution; however, this result adds information regarding the ethnic group being studied here. Also we employed long down-regulated protocol because at the time of study antagonist agents were unavailable to us. Lastly, since the measurement of AMH by Gen II assay is subject to the complement interference which may overestimate or underestimate the actual AMH values, further studies with the use of new protocols even in the already studied populations are justified .We suggest that infertile patients undergoing COH with top and low quartile basal AMH values are at high risk for OHSS and poor ovarian response, respectively. Reduced stimulation dosage in high risk subjects for OHSS had no detrimental effect on the final outcome. Our study indicated that AMH was a superior predictor to traditional factors including age, BMI, and PCOS. Also considering that AMH is available before the stimulation, it is superior to the number of oocytes yielded.


Left ventricular hypertrophy (LVH) is known to be associated with all-cause mortality and morbidity. There is a strong relationship between LV mass and afterload but the influence of aortic vasculopathy on ventricular geometry is less well understood. Aortic stiffness (AS) is one of the earliest detectable signs of the changes that alter the structure and function of the vessel wall, and may precede the onset of systemic hypertension and ventricular hypertrophy. The aim of this study was to determine the changes in LV geometry associated with aortic pulse wave velocity (PWV) using 3D cardiac imaging of the heartPhase contrast imaging was performed in 403 healthy volunteers using a single axial section to image both the aortic root and descending thoracic aorta. PWV was calculated using Art-Fun  software to detect the systolic upstroke of the flow profile and measure the path length of the aortic arch. High-spatial resolution breath-hold 3D cine imaging was performed of the LV. Each image was segmented and co-registered using prior knowledge from a cardiac atlas. Wall thickness was calculated at each point as the distance between endocardial and epicardial surfaces. Linear regression was used to model to association between variablesUnivariate analysis showed a strong correlation between PWV vs age  and PWV vs mean arterial blood pressure . In multivariate analysis, both age  and MAP  were independent predictors of PWV. The 3D models showed that 55% of the variation in left ventricle wall thickness can be accounted for by a linear model that includes PWV, age, gender, race, and BSA as co-variates. The models demonstrated strong regional associations between PWV and wall thickness which may reflect adaptations to normalize wall shear stress in the LVThis study of healthy volunteers showed that age is the strongest independent predictor of PWV and that the associated morphological adaptations of the LV may be modelled in 3D. This computational approach to phenotyping may provide insights into the physiological adaptations in the LV associated with vascular functionSaudi Ministry of Higher Education.


Myocarditis subsumes a variety of entities, including diverse courses from complete healing to dilated cardiomyopathy with severe myocardial fibrosis. T1-mapping cardiovascular magnetic resonance (CMR) has the ability to quantify myocardial extracellular volume (ECV) as a surrogate of acute and chronic myocardial injury. Galectin-3 is an important mediator of fibrogenesis and contributes to adverse left ventricular (LV) remodeling. This study evaluated, if myocardial ECV expansion is linked to Galectin-3 levels in patients with myocarditis.Galectin-3 blood levels were measured in 20 patients with myocarditis using a commercially available chemiluminescent microparticle immunoassay . T1 quantification was performed at 1.5 Tesla using the modified Look-Locker inversion-recovery (MOLLI) sequence before and 15 minutes after administration of 0.075 mmol/kg gadolinium-BOPTA. Global myocardial ECV was calculated from T1 maps generated by a dedicated plug-in written for the OsiriX software.Median Galectin-3 level was 17.4 ng/mL (interquartile range 13.2 to 20.5 ng/mL) and median global myocardial ECV was 29 % (interquartile range 26 to 33 %) in the study population. There was a significant correlation between Galectin-3 levels and global myocardial ECV . In contrast, no significant correlation was found between Galectin-3 levels and LV end-diastolic volumes , LV end-systolic volumes , LV stroke volumes ; LV ejection fractions , Troponin T levels  or NT-proBNP levels , respectively.Myokardial ECV expansion, as a surrogate for myocardial injury, is associated with increased Galectin-3 levels, indicating activated fibrogenesis in patients with myocarditis. Combining Galectin-3 measurements with ECV-imaging could improve risk stratification beyond conventional imaging parameters or biomarkers in these patients.Marija-Orlovic-Foundation.


P = 0.034) and Scond  were higher in the heart failure patients. There was no difference in Sacin . Measures of ventilation heterogeneity did not change in the supine position. This study confirms the presence of peripheral airway pathology in patients with chronic heart failure. This leads to subtle but detectable functional abnormalities which do not change after 45 min in the supine position.In the healthy lung, ventilation is distributed heterogeneously due to factors such as anatomical asymmetry and gravity. This ventilation heterogeneity increases pathologically in conditions such as asthma, chronic obstructive lung disease, and cystic fibrosis. In chronic heart failure, lung biopsy demonstrates evidence of peripheral lung fibrosis and small airways narrowing and distortion. We hypothesized that this would lead to increased ventilation heterogeneity. Furthermore, we proposed that rostral fluid shifts when seated patients lie supine would further increase ventilation heterogeneity. We recruited 30 ambulatory chronic heart failure patients  as well as 10 healthy controls . Heart failure patients were clinically euvolemic. Subjects underwent measurement of ventilation heterogeneity using the multiple-breath nitrogen washout technique in the seated position, followed by repeat measurements after 5 and 45 min in the supine position. Ventilation heterogeneity was calculated using the lung clearance index (LCI), Sacin and Scond which represent overall, acinar, and small conducting airway function, respectively. Lung clearance index (9.6 ± 1.2 vs. 8.6 ± 1.4 lung turnovers,  Patients with chronic heart failure (CHF) are exposed to increased pulmonary capillary pressures which can result in injury to the pulmonary capillaries in a processed termed pulmonary capillary fracture  falls with increasing pulmonary artery wall thickness in heart failure patients  has been used to detect early changes in small airway function in a variety of disease states including smoking, chronic obstructive pulmonary disease, bronchiolitis obliterans, and asthma . We recruited ambulatory patients with known CHF due to left ventricular systolic failure from our institution’s heart failure service as well as healthy controls. Heart failure patients were ambulatory and clinically stable.2. Nitrogen concentration was continuously monitored at the mouth , while flow and volume were calculated by volume displacement from within the double bag-in-box system and measured by pneumotachography . Participants continued to breathe O2 until nitrogen was washed out to below 2%. This test was repeated three times in each position  with sufficient time allowed for complete re-equilibration of nitrogen within the lung functional residual capacity before subsequent testing was commenced  was performed in both the seated and supine positions. Testing in the supine position was performed after 5 and 45 min of lying in the supine position. Testing at 5 min was done to control for any affect positional change would have of ventilation heterogeneity while testing was performed after 45 min based on data which suggest most lower limb fluid shifts have occurred in this time  and results presented as mean ± standard deviation unless otherwise noted.Thirty chronic heart failure patients and 10 healthy controls were recruited. One heart failure patient was found to have reversible airways obstruction on spirometry and a second patient was found to have bronchiectasis on CT chest, both were excluded from the analysis. Mean duration of heart failure diagnosis was 8.9 ± 8.5 years. Demographic and lung function data of the two groups are shown in Tablesn = 20) and 32 ± 16% on gated cardiac blood pool scan (n = 12). Of these, seven patients had both tests while the three remaining patients had documented left ventricular dysfunction but no recorded left ventricular ejection fraction. Eight patients had a right heart catheter within a week of the MBNW. They had a pulmonary artery wedge pressure of 16 ± 8 mmHg , a cardiac index of 2.2 ± 0.4 L/min/m2 (2.6–4.2L/min/m2) and a pulmonary vascular resistance of 3.1 ± 1.1 Wood units (0.25–1.6 Woods units).Chronic heart failure patients had a mean ejection fraction of 30 ± 12% on transthoracic echocardiogram (Heart failure patients were found to have higher LCI and Scond than controls. There was no significant difference in Sacin between CHF patients and control subjects see Table.There was no change in any measure of ventilation heterogeneity after 5 and 45 min in the supine position in either group (see Tablen = 12) and heart failure ever smokers (n = 16) revealed no significant difference between the two subgroups in any measure of ventilation heterogeneity. There continued to be a difference in Scond between the heart failure nonsmokers and controls when the smokers were removed from the analysis, while LCI just failed to reach statistical significance most likely due to a loss of statistical power .Another weakness of our study is that we did not have a direct histopathological or radiological measure of the parenchymal changes we have proposed as a reason for the increased ventilation heterogeneity in heart failure. Given such changes were described at an electron microscope level in lung biopsy specimens it is unlikely they could be quantified using radiological imaging alone. Obtaining lung biopsy specimens for a study such as ours would be unnecessarily invasive. TLCO has been shown to be a good measure of the pulmonary vascular changes which occur in association with parenchymal change (Aber and Campbell Ventilation heterogeneity (lung clearance index and Scond) is increased in chronic heart failure. Supine position does not affect ventilation heterogeneity in either heart failure or controls. Further studies are required to determine the clinical impact of increased ventilation heterogeneity in these patients.


Objective. Using a swine model of acute myocardial ischemia, we sought to validate N-11C-methyl-dopamine (11C-MDA) as an agent capable of imaging cardiac sympathetic nerve injury. Methods. Acute myocardial ischemia was surgically generated in Chinese minipigs. ECG and serum enzyme levels were used to detect the presence of myocardial ischemia. Paired 11C-MDA PET and 13N-ammonia PET scans were performed at baseline, 1 day, and 1, 3, and 6 months after surgery to relate cardiac sympathetic nerve injury to blood perfusion. Results. Seven survived the surgical procedure. The ECG-ST segment was depressed, and levels of the serum enzymes increased. Cardiac uptake of tracer was quantified as the defect volume. Both before and immediately after surgery, the images obtained with 11C-MDA and 13N-ammonia were similar. At 1 to 6 months after surgery, however, 11C-MDA postsurgical left ventricular myocardial defect volume was significantly greater compared to 13N-ammonia. Conclusions. In the Chinese minipig model of acute myocardial ischemia, the extent of the myocardial defect as visualized by 11C-MDA is much greater than would be suggested by blood perfusion images, and the recovery from myocardial sympathetic nerve injury is much slower than the restoration of blood perfusion. 11C-MDA PET may provide additional biological information during recovery from ischemic heart disease. Cardiovascular disease is the leading cause of death worldwide , and myo123I metaiodobenzylguanidine (123I-MIBG) and 11C-hydroxyephidrine (11C-HED) are norepinephrine analogs [18F-Fluorodopamine (18F-DA) is an imaging agent used for the evaluation of primary or secondary lesions in sympathetic tissue [18F-DA is expensive and produces low yields, and these problems have limited its use.Several compounds have been used for sympathetic nerve receptor imaging in preclinical or clinical studies –16. Both analogs , 18, whi analogs . However analogs . 6-18F-Fc tissue , 22. How N-11C-methyl-dopamine (11C-MDA) for cardiac sympathetic nerve imaging. The biological properties of 11C-MDA were evaluated in normal mice and healthy Chinese minipigs [11C-MDA had a high myocardium uptake in biodistribution studies. It could be clearly imaged in the heart by PET/CT, and this uptake was blocked by imipramine hydrochloride. Therefore, 11C-MDA is a promising candidate radiotracer for imaging the cardiac sympathetic nervous system.We have recently synthesized a novel tracerminipigs . 11C-MDA11C-MDA and 13N-ammonia for myocardial blood perfusion. In this way, we were able to observe cardiac sympathetic nerve injury and recovery over a period of 6 months.In this study, we established a model of acute myocardial ischemia in Chinese minipigs. Animals were imaged by PET/CT with 11C-MDA and 13N-ammonia were synthesized in-house in our PET center cyclotron facility as previously described [11C-MDA and 13N-ammonia. Radiopharmaceuticals were passed through a 0.2 μm membrane filter for in vivo use.escribed . RadiochThe study reported here, as well as all aspects of animal maintenance and welfare, was approved by the Inner Mongolian Medical University Animal Care and Use Committee. Ten Chinese minipigs  were maintained in our large animal facility, housed singly, and supplied with the standard diet for swine.Surgery was performed as follows: Animals were fasted for 6 hours and intramuscularly injected with ketamine (20 mg/kg) and diazepam (2 mg/kg) for anesthesia; an intravenous route was established at the ear vein and propofol (2 mg/kg/h) was infused to maintain anesthesia. Pigs were placed on the operating table and connected to ECG and oxygen monitor. After successful intubation, the animal underwent ventilator-assisted breathing . Hair on the chest was shaved, and the skin was disinfected with 0.1% benzalkonium bromide solution. As shown in The onset of ischemia was identified by an increase or decrease in the ECG-ST segment of 0.2 mV. Coronary artery occlusion was then released to form acute myocardial ischemia model. Intraoperative electrocardiographic monitoring and venous blood serum enzyme examination  at 9–12 hours after surgery were conducted in all subjects.11C-MDA (74 MBq) and, 10 minutes later, given a 20-minute thoracic PET scan followed by CT. Six hours later, animals received intravenous 13N-ammonia (555 MBq) and, after 5 minutes, a 20-minute thoracic PET scan. A clinical PET/CT scanner  was used for 2D nongated PET acquisition, and low dose CT was always performed for attenuation correction  before each PET scan.Chinese minipigs were fixed supinely in a special wooden frame and anesthetized as described above. Animals were injected with After acquisition, images were transferred to Xeleris  and AW  image processing workstation for image interpretation and semiquantitative analysis. All image reconstruction was conducted by Butterworth filter function, and the short axis, horizontal long axis, and vertical long axis of the three cross-sectional images were presented. t-test was used to compare the effect of treatment on the same imaging agent and an unpaired t-test was used to compare the results of two imaging agents. ANOVA was used to analyze the cardiac defect volumes of both imaging agents. SPSS13.0 software (IBM) was used for statistical analysis. A P value less than 0.05 was considered statistically significant.Data are presented as the mean ± SD. A pairedOf the ten pigs that underwent surgery, 7 survived and were available for 6 months of follow-up. Evidence of acute myocardial ischemia was present in all 7 animals. The ECG-ST segment was depressed by over 0.2 mV at lead II . Blood s11C-MDA PET showed uniform distribution of radioactivity in the left ventricular myocardium and mild uptake in the right ventricular wall, which was broadly similar to 13N-ammonia myocardium images  imaging was greater than that suggested by myocardial blood perfusion imaging [11C-HED retention, while 13N-ammonia was unperturbed [11C-MDA provides more information than blood perfusion imaging for evaluation of post-acute ischemia induced myocardium injury and recovery.In this study, we established acute cardiac ischemia model in Chinese minipig Figures  and 2; w Figures . Unfortu imaging . In 8 paerturbed . AccordiDamage to nervous tissue is an inevitable consequence of myocardial ischemia or infarction, and activation of sympathetic reflex leads to increased vasospasm. As the nutrient supply is restricted and metabolic waste products cannot be efficiently cleared, further nerve damage ensues. Moreover, ATP pools in nerve terminals become depleted, also triggering damage to the nerve endings, and this damage is generally beyond repair. Reperfusion and calcium release from endothelial cells also contribute to damage.18F-DA imaging, Fallen et al. [11C-MDA PET/CT imaging could successfully detect abnormal sympathetic tissue in the damaged heart (Figures The study also found that myocardial ischemia-reperfusion and cardiac sympathetic restoration occurred over different time scales Figures –6. This n et al.  found thn et al. , and at n et al. , 31. Symn et al. , and in n et al. , includin et al. , 35. Our Figures  and 5, a11C-MDA PET imaging sympathetic nerve recovery with 13N-ammonia for blood perfusion; dynamic PET acquisition immediately after tracer inoculation was not conducted in this study. Dynamic PET data analysis for compartment modeling was not performed in this study, and a future study may need to focus on this issue.The objective of this study was to compare 11C-MDA is capable of imaging cardiac damage and provides information that is distinct from blood perfusion imaging. 11C-MDA PET may provide additional biological information during recovery from ischemic heart disease.Using a Chinese minipig model of acute myocardial ischemia, we have demonstrated that


Cardiovascular MRI (CMR) has the advantages of high temporal and spatial resolution with excellent endocardial definition, but ECG-gated cine SSFP imaging requires multiple sequential breath-holds and is time-consuming. Sparse sampling with iterative reconstructionallows for ultra-fast acquisitions of SSFP cine images. The accuracy of this technique compared to standard SSFP imaging requires further validation in the clinical setting.2), requiring 10-14 breath-holds of 10-15s, and then repeated with an ECG-triggered prototype TrueFISP sequence  with a constrained undersampling resulting in a net acceleration factor of 4 (CV_sparse), acquired in a single breath-hold or two breath-holds (depending on cardiac size). For the CV_sparse approach, coil sensitivity maps were calculated from the temporal average of the input data in a central region of k-space and image data were then reconstructed using a non-linear iterative reconstruction with k-t regularization of the SENSE type dataset. Datasets were analysed by two experienced readers , with papillary muscles and trabeculae included in the blood pool. Comparison of TrueFISP and CV_sparse was assessed using paired t-test and Pearson's correlation, and inter-observery reproducibility by Bland-AltmanProspective, observational study of clinical patients referred for CMR imaging for left ventricular evaluation, performed on a Siemens Magnetom Aera 1.5T scanner in a large, tertiary clinical service. All patients had a standard left ventricular short axis stack using standard ECG-triggered TrueFISP imaging , end-systolic volume , LVmass  and LVEF , with no difference between the groups (P=0.95 NS), figurefigurep<0.001), however CV_sparse images require longer reconstruction times (~5 minutes), during which clinical image acquisition can continue.26 clinical patients had both TrueFISP and CV_sparse imaging successfully performed figure, mean LVHighly accelerated imaging using TrueFISP with sparse sampling and iterative reconstruction provides excellent image quality with accurate, reproducible results equalling those of standard TrueFISP imaging, but with significantly more rapid acquisition times. This accelerated technique appears valid and ready for application to clinical practice.Smart Futures Fellowship Early Career Grant (Queensland State Government #ISF783).


Objective: To evaluate differences in LV rotational mechanics acquired during breath holding (BH), free-breathing with averaging (AVG), and free-breathing with respiratory bellows gating (BEL).Patients with Duchenne Muscular Dystrophy (DMD) develop respiratory impairment and signs and symptoms of cardiac involvement at an early age. Quantitative measures of cardiac function from MRI tagging can be used to stage disease progression and monitor the response to therapy. Traditional cardiac MRI exams, however, require repeated breath holding, which places a notable burden on patients with DMD and can impart intrathoracic pressure changes that alter cardiac function. The effect of free-breathing on quantitative measure of left ventricular (LV) rotational mechanics for DMD patients is incompletely understood. 16 healthy volunteers  and 5 DMD patients  were scanned on a 3.0T Siemens Scanner with BH, AVG and BEL. ORI-SPAMM :339-345) was used to acquire short-axis images at the base and apex of the heart. 280-330x280-330mm field-of-view, 6mm slice thickness, 192x192 acquisition matrix, 395 Hz/pixel receiver bandwidth, TE/TR =2.33-2.39/4.71-4.83 ms, 8 phase encode lines per segment, 12° imaging flip angle, 8 mm tag spacing, GRAPPA 2. LV twist and circumferential-longitudinal shear (CL-shear) angle were calculated using the Fourier Analysis of STimulated echoes (FAST) method :587-593).Figure The observed increase in end systolic epicardial radius during BEL compared to BH indicates that afterload is increased which accords with a decrease in twist. The decrease in rotation combined with the increase in end-systolic radii cause CL-shear angle to pseudo-normalize. Overall, a free breathing strategy is a preferred method for patients with limited breath hold ability due to the non-negligible difference between BH and BEL results. However, for longitudinal studies where breath-hold conditions cannot be controlled CL-shear angle may be a better measure of rotational mechanics.AHA 13BGIA14530010 to Daniel B. Ennis and AHA 11PRE6080005 to Meral L. Reyhan


Iron may damage sarcomeric proteins through oxidative stress. We explored the left ventricular (LV) torsional mechanics in patients with beta-thalassaemia major and its relationship to myocardial iron load. Using HL-1 cell and B6D2F1 mouse models, we further determined the impact of iron load on proteolysis of the giant sarcomeric protein titin.* cardiac magnetic resonance findings correlated with resting diastolic untwisting velocity. The increments from baseline and resultant LV torsion and systolic and diastolic untwisting velocities during exercise were significantly lower in patients than controls. Significant correlations existed between LV systolic torsion and diastolic untwisting velocities in patients and controls, both at rest and during exercise. In HL-1 cells and ventricular myocardium of B6D2F1 mice overloaded with iron, the titin-stained pattern of sarcomeric structure became disrupted. Gel electrophoresis of iron-overloaded mouse myocardial tissue further showed significant decrease in the amount of titin isoforms and increase in titin degradation products.In 44 thalassaemia patients aged 25 ± 7 years and 38 healthy subjects, LV torsion and twisting velocities were determined at rest using speckle tracking echocardiography. Changes in LV torsional parameters during submaximal exercise testing were further assessed in 32 patients and 17 controls. Compared with controls, patients had significantly reduced LV apical rotation, torsion, systolic twisting velocity, and diastolic untwisting velocity. T2Resting and dynamic LV torsional mechanics is impaired in patients with beta-thalassaemia major. Cell and animal models suggest a potential role of titin degradation in iron overload-induced alteration of LV torsional mechanics. Iron overload cardiomyopathy is well documented in patients with beta-thalassaemia major. Nonetheless, the left ventricular (LV) function usually remains relatively normal as assessed by conventional echocardiographic imaging until late in the cardiomyopathic process . These cLeft ventricular torsional mechanics plays an important role with respect to LV ejection and filling ,8 and isChanges at a cellular level may perhaps also be reflected by alterations of LV torsional mechanics. Transplanted human hearts in early rejection have been shown to display alterations in systolic twisting and diastolic untwisting patterns . RemodelIn this prospective study, we explored the resting and dynamic LV torsional mechanics in patients with beta-thalassaemia major and its relationship with myocardial iron load. Given the initial echocardiographic findings of impaired LV torsion, systolic twisting and diastolic untwisting velocities in patients compared with healthy subjects, we further determined using HL-1 cell and mouse models of iron overload the impact of iron load on titin proteolysis.Forty-four patients with beta-thalassaemia major and normal LV shortening fraction as assessed by two-dimensional echocardiography were recruited. Patients with diabetes mellitus and thyroid dysfunction were excluded. The chelation therapy of patients was noted. Thirty-eight healthy subjects were recruited as controls. These included healthy siblings of thalassaemia patients and voluntary staff members and their friends and relatives. The Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster approved the study and all of the patients gave informed written consent.All subjects rest for at least 15 minutes before blood pressure and cardiovascular assessments. The body weight and height were measured and the body mass index and body surface area calculated accordingly. For thalassaemic patients, the study was performed within one week of blood transfusion to minimize potential confounding influence of anaemia on the assessment results.Echocardiographic assessments were performed using the Vivid 7 ultrasound machine . All of the following echocardiographic data were obtained at rest. The parameters of torsional mechanics were obtained both at rest and during submaximal exercise. The average values of echocardiographic indices from three cardiac cycles were used for analyses.Left ventricular torsion was assessed by two-dimensional speckle tracking echocardiography as reported previously . BrieflySubmaximal exercise testing was performed with a supine bicycle according to the McMaster cycle ergometer protocol . The ini* cardiac magnetic resonance (CMR) was performed as described previously [T2eviously  and in d3 for 72 hours.HL-1 cardiomyocytes were kindly provided by Professor W.C. Claycomb  . These cIron-loaded mouse model was generated as described previously . Seven-wHL-1 cells were fixed and permeated with Cytofix/Cytoperm™ solution , followed by washes with Perm/Wash™ buffer . Non-specific antibody binding was blocked by incubation with 5% bovine serum albumin (BSA). Titin PEVK domain was stained with primary antibody 9D10  1:100 diluted in 5% BSA, followed by secondary antibody Cy™5  1:100 diluted in 5% BSA. Nuclei were counterstained with DAPI. The patterns of titin staining were analyzed by Zeiss LSM 510 Confocal Microscope .For determination of titin pattern in mouse heart tissue, 7 μm-thick cryosection slides of heart tissue were fixed and permeated with 0.2% PBST, and then blocked with 10% normal rabbit serum (NRS) in 0.2% PBST. Titin was stained with antibody 9D10 in 5% NRS and subsequently with the secondary antibody same as aforementioned. Confocal images were analyzed by software ImageJ .25 with details provided in Additional file Titin was analyzed in ventricular extracts  using gel electrophoresis as described previouslyt test. The resting and exercise echocardiographic indices were compared by paired Student’s t test, while the magnitude of changes in torsional indices from the resting to exercise state in patients and controls was compared by unpaired Student’s t test. Relationships between systolic torsion and diastolic untwisting velocity at rest and exercise of the entire cohort and within patient and control groups, and associations between torsional indices and iron load were assessed by Pearson correlation analysis. In-vitro study data are presented as mean ± SEM and variables between two groups were compared by unpaired Student’s t test. Statistical analyses were performed using SPSS version 16  and GraphPad Instat 3 . A p < 0.05 was regarded as statistically significant.Clinical data are presented as mean ± SD. The demographic and echocardiographic parameters of patients were compared with those of control subjects using unpaired Student's * cardiac magnetic resonance performed in 31 patients, 8 patients had evidence of myocardial iron overload (T2* ≤ 20 ms). All of the patients were free from cardiac symptoms. Thirty-eight  healthy young adults aged 23 ± 6 years (p = 0.10) were recruited as controls. Patients compared with controls were lighter  and had a smaller body surface area .Forty-four patients  aged 25 ± 7 years were recruited. Chelation therapy regimen at the time of study were deferiprone with deferoxamine in 26 patients, deferasirox in 9, deferoxamine in 7, and deferiprone in 2. Based on T2*values >20 ms, the LV apical rotation, torsion, and systolic twisting velocities were significantly lower than those of controls. While these parameters were also lower in the 8 patients with myocardial iron overload (T2* ≤ 20 ms), the small number limits the power to detect statistical significant differences in these variables except for apical rotation. T2* findings correlated inversely with LV diastolic untwisting velocity , but not with peak systolic torsion (p = 0.54) twisting velocity (p = 0.65). Hence, the greater the myocardial iron load, the lower the diastolic untwisting velocity.At baseline, patients had significantly lower LV torsion, systolic twisting velocity, and diastolic untwisting velocity compared with controls  Table . The sig*findings and the various LV torsional parameters during submaximal exercise .Thirty two patients and 17 controls agreed to undergo further submaximal exercise testing in the exercise laboratory. During supine bicycle exercise testing, both patients and controls showed significant increase in peak LV torsion and systolic twisting and diastolic untwisting velocities   impaired LV torsional mechanics in patients with beta-thalassaemia major at rest, 2) diminished incremental response of systolic twisting and diastolic untwisting parameters during submaximal exercise stress, 3) coupling of systolic torsion and rate of diastolic untwisting, 4) an inverse relationship between myocardial iron load and LV diastolic untwisting velocity, and 5) evidence of titin disruption and degradation in cell and mouse models of iron load, implicating its potential pathogenetic role in causing abnormalities of resting and exercise LV torsional mechanics found in patients clinically.* value (≤20 ms) [* ≤ 20 ms) and without (T2* > 20 ms) significant myocardial iron load and decreased LV torsion only in those with T2* ≤ 20 ms compared with controls [The understanding of torsional mechanics in patients with beta-thalassaemia major has been limited. Using vector velocity imaging, Gareau et al. have recently reported on reduced LV torsion and apical rotation in patients with beta-thalassaemia major and Blackfan-Diamond anaemia with low T2(≤20 ms) . Assessmcontrols . Differecontrols .* values have also been shown to correlate with CMR-derived early to late diastolic ventricular filling [While our findings corroborate those reported previously, we found additionally significant reduction of rates of LV systolic twisting and diastolic untwisting in our patient cohort. Albeit modest and without implications on causality, the inverse relationship between iron load and diastolic untwisting velocity may have pathophysiologic significance. Rapid LV diastolic untwisting has been shown to correlate with the time constant of relaxation during isovolumic relaxation  and intr filling .Using dobutamine stress echocardiography, we  and otheClose correlations between systolic torsion and diastolic untwisting velocity in our patients and controls both at rest and during exercise reflect systolic-diastolic coupling, a phenomenon demonstrated previously in normal subjects at rest ,37 and dTitin, the largest protein in the body, acts as a structural, elastic, and signaling molecule in cardiomyocytes . In partDetection in our patient cohort of abnormal LV systolic and diastolic torsional parameters despite normal conventional and tissue Doppler indices of LV function suggests the greater sensitivity of torsional parameters in detecting subtle LV dysfunction in thalassaemia major, although the use of these parameters in accurate quantification of myocardial iron load appears limited. As alluded to earlier, altered LV untwisting may perhaps contribute to impaired exercise capacity documented in thalassaemia major patients . Our demSeveral limitations to this study warrant comments. Firstly, our patients are relatively young with no congestive heart failure. Whether the findings hold true for those with clinically manifested iron induced cardiomyopathy require further studies for confirmation. Nonetheless, impaired LV torsional mechanics has been well documented in other causes of heart failure ,10. SecoThis study demonstrates impaired resting and dynamic LV torsional mechanics in patients with beta-thalassaemia major. Furthermore, we found in these patients a close relationship between LV systolic torsion and diastolic untwisting and an association between myocardial iron overload and worse diastolic untwisting. Importantly, cell and animal models of iron overload provide a novel piece of evidence for a potential role of titin degradation in the alteration of LV torsional mechanics observed in patients.The authors declare that they have no competing interests.YFC has been involved in design and overall supervision of the study. SNL recruited the subjects and performed the echocardiographic studies and analyses. MPC carried out all the experiments. SNL and MPC contributed equally to the writing of the manuscript. WWL and YCH performed the cardiac magnetic resonance and interpreted the data. SY Ha and GCC recruited the subjects and interpreted the data. All of the authors critically revised the manuscript and have read and agree to the manuscript as written.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2261/14/49/prepubSupplementary methods.Click here for file


Left ventricular noncompaction cardiomyopathy is a rare myocardial disorder which results from failure of left ventricle to compact in embryogenesis. We present a case of a 53-year-old female who came because of abdominal pain and was found to have renal infarct secondary to noncompaction cardiomyopathy. Left ventricular noncompaction is a rare form of genetic cardiomyopathy that occurs due to arrest in the compaction of developing myocardium which leads to deep trabeculae and recesses giving the ventricle a spongiform appearance –4. It haA 53-year-old female with a history of hypertension presented with the complaints of left sided back pain and dysuria for 2 days. Patient denied any history of chest pain, shortness of breath, or any cardiac problems in the past. Physical examination was significant for bibasilar crackles and pedal edema but no costovertebral tenderness. There was no family history of cardiomyopathy or heart failure. Routine labs showed hemoglobin, 10.5; white cell count, 6.4; platelets, 391. Renal and liver functions tests were within normal limits. An EKG test was done on admission which showed normal sinus rhythm and left axis deviation but no significant ST-T wave changes. Urine analysis was done which was negative for urinary tract infection. CT scan of abdomen  was first described in 1975 by Dusek et al.  as lack LVNC is a genetically heterogeneous disorder and both familial and sporadic forms have been described. Mutations in various genes –12 have The incidence of isolated noncompaction varies among different studies but has been noted to be anywhere between 0.014 and 1.3%. A lot of patients with LVNC are diagnosed during the neonatal period. A significant number of these patients have undulating phenotype in which they have transient recovery of function and present with symptoms later in adult life. Most of the times in children, LVNC usually coexists with other genetic conditions like Barth syndrome, Emery-Dreifuss muscular dystrophy, myotubular myopathy, and so forth, in contrast to adults where it has been known to occur in isolation. It is still unclear whether presentation of LVNC in adulthood represents a long standing condition or delayed manifestation of molecular pathology. With increasing awareness of this rare condition and better and more specific echocardiographic diagnostic parameters, the prevalence of this condition has increased.The most common forms of presentation include heart failure, arrhythmias, and systemic embolism , 6, 7. IA thickened ventricular wall consisting of two layers, a thin compacted epicardial layer and a markedly thickened endocardial layer with numerous trabeculations and deep recesses with a maximum ratio of noncompacted to compacted myocardium of >2 : 1 at the end systole in the parasternal short axis view.Color Doppler evidence of flow within the deep intertrabecular recesses.Prominent trabecular meshwork in the LV apex or midventricular segments of inferior and lateral wallEchocardiography with color follow Doppler has been considered as the diagnostic modality of choice for diagnosis of this rare cardiomyopathy and specific criteria for diagnosis have been put forward by various researchers , 15–18. Our patient had an echocardiogram which showed a noncompacted to compacted myocardium ratio of >2 : 1 at the ventricular apex prominent trabecular meshwork in the LV apex and color Doppler evidence of flow in the recesses thus making a diagnosis of LVNC.Cardiac magnetic resonance imaging (Cardiac MRI) has been increasingly used for diagnosis of noncompaction cardiomyopathy as it provides a detailed image of cardiac morphology. Cardiac MRI is particularly useful in patients in whom the apex is difficult to visualize with echocardiography or in whom the diagnosis is uncertain with conventional echocardiography. A noncompacted/compacted ratio >2.3 measured at end diastole is used as the diagnostic indicator for noncompaction cardiomyopathy . A studySymptoms of heart failure are the most commonly presenting symptoms in LVNC. Tian et al.  found inSudden cardiac death is another concern in these patients and should always be evaluated for presence of sustained/nonsustained ventricular tachycardia. The incidence of ventricular arrhythmias varies from 6%  to 62% , implantSystemic embolism is another complication associated with LVNC. Initially it was thought to result from stagnation of flow across the prominent trabeculations and deep recesses leading to clot formation in noncompacted layer. A retrospective review done by Stöllberger and Finsterer  found thStudies on asymptomatic patients with normal EF failed to show any increased risk of systemic embolism and therefore use of anticoagulation in this patient population remains controversial .Large case series done by Lofiego et al.  and GreuA recent retrospective review done by Tian et al.  in 106 pAnother recent study  done on While LVNC is not common, its prevalence has increased due to better imaging modalities and more specific diagnostic criteria but still this disease may be underdiagnosed due to lack of awareness among clinicians. Our case illustrates an uncommon presentation of LVNC with renal infarction as the presenting manifestation which later leads to finding of severely decreased LV function and diagnosis of LVNC. It is important to recognize that this condition as the management of LVNC is slightly different from other causes of LV dysfunction such as the need to anticoagulate because of the high risk of thromboembolism and the familial inheritance requiring genetic counselling, screening among family members.This makes the disease, its presentations, complications, and management important for the general internist and the cardiologist to know.Echocardiographic apical two chamber view showing the non-compacted myocardium most prominent at the apex.