To assess intervendor agreement of cardiovascular magnetic resonance feature tracking (CMR-FT) and to study the impact of repeated measures on reproducibility.42, Calgary, Canada) to assess global left ventricular circumferential (Ecc) and radial (Err) strains and torsion. Differences in intra- and interobserver variability within and between software types were assessed based on single and averaged measurements  as determined by Bland–Altman analysis, intraclass correlation coefficients (ICC), and coefficient of variation (CoV).Ten healthy volunteers underwent cine imaging in short-axis orientation at rest and with dobutamine stimulation (10 and 20 μg/kg/min). All images were analysed three times using two types of software . Resting Ecc and torsion as well as Ecc values during dobutamine stimulation were lower measured with Circle (p<0.05). Intra- and interobserver variability between software types was lowest for Ecc  irrespective of the number of analysis repetitions. Err and torsion showed higher variability that markedly improved for torsion with repeated analyses and to a lesser extent for Err. On an intravendor level TomTec showed better reproducibility for Ecc and torsion and Circle for Err.Myocardial strains and torsion significantly increased on dobutamine stimulation with both types of software (CMR-FT strain and torsion measurements are subject to considerable intervendor variability, which can be reduced using three analysis repetitions. For both vendors, Ecc qualifies as the most robust parameter with the best agreement, albeit lower Ecc values obtained using Circle, and warrants further investigation of incremental clinical merit. •This is the first comparison of two types of CMR-FT software resulting in clinically valuable inter-vendor agreement data.•Assessment of myocardial strain and torsion is feasible with both types of software at rest and with dobutamine stimulation.•For both vendors, Ecc qualifies as the most robust parameter with the lowest variability. Given the fact that a widespread clinical use of these new measures of deformation is highly desirable and likely important, prerequisites to achieve this goal are to ensure that the assessments are reproducible and comparable with a high amount of intervendor agreement. Therefore, the aim of the present study was to assess the reproducibility and intervendor agreement of both commercially available types of software for the derivation of ventricular circumferential (Ecc) and radial (Err) strains, as well as rotational mechanics expressed as left ventricular (LV) torsion.Heart failure is characterised by high mortality irrespective of the predominance of either systolic or diastolic functional impairment.The study cohort consisted of 10 healthy volunteers. CMR imaging was carried out on a 1.5 T system . All participants gave written informed consent after approval of the study protocol by the Institutional Review Board at the University of Nebraska Medical Center.The CMR examination was carried out in the supine position using a five-channel cardiac surface coil. Electrocardiogram (ECG)-gated SSFP cine sequences were acquired during brief periods of breath-holding in 12 to 14 equidistant short-axis planes completely covering the LV. Typical CMR parameters were as follows: 8 mm section thickness; 1–2 mm gap; 360×480 mm field of view; 196×172 matrix size. Dobutamine stress CMR imaging was performed as previously described.42). For the purposes of this paper the different software tools are referred to as “TomTec” and “Circle”. Identical short axis sections were analysed at apical, mid-ventricular, and basal levels to compare short-axis-derived global LV Ecc and Err  alongside the time-to-peak (TPK) strain duration. Short-axis CMR images were analysed at rest and with 10 and 20 μg/kg/min dobutamine, respectively. Myocardial torsion was calculated from the rotational raw data provided with the TomTec software using an in-house-developed post-processing tool as recently described by the authors' group.CMR-FT was performed using dedicated software provided by TomTec Imaging Systems  and Circle Cardiovascular Imaging . To study the impact of repeated measurements on reproducibility, the reproducibility derived from results based on a single repetition (R1), averaged results for two (R2) and three repetitions (R3) were compared with each other.Statistical analysis was conducted using Microsoft Excel and IBM SPSS Statistics version 22 for Windows. Data are expressed as mean (± standard deviations). Pairwise non-parametric data at rest and with increasing levels of dobutamine were compared using the Wilcoxon test. Significance was determined at <0.05. The intra- and interobserver variability was assessed using three different methods: intraclass correlation coefficients (ICC), Bland–Altman analysis,Demographics are displayed in p<0.05) using TomTec  and with 10 (p<0.05) and 20 μg/kg/min of dobutamine  but not between 10 and 20 μg/kg/min of dobutamine . There were significantly increased strain values with dobutamine stress as compared to rest irrespective of the number of analysis repetitions .Err significantly increased from rest to 20 and between 10 and 20 μg/kg/min of dobutamine using Tom Tec p<0.05; . The corp=0.125; . With Cip<0.05; p=0.13). All other comparisons reached statistical significance (p<0.05) (p<0.05). There was no significant difference in torsion derived from either software during dobutamine stress .A significant increase in myocardial torsion was measured between rest and both levels of dobutamine, but not between 10 and 20 μg/kg/min of dobutamine using either software type p<0.05; , Table 2Intervendor variability was lowest for Ecc, and higher for myocardial torsion and Err on an intra- and interobserver level based on three analysis repetitions R3; . InterveThe results based on three repetitions (R3) are shown in To the authors' knowledge, this study is the first comparison of different types of commercially available CMR-FT software, and presents several notable findings. First, intervendor agreement between the two software types is reasonable, with the best agreement for Ecc, and worse but acceptable agreements for myocardial torsion and Err. Second, there is significantly lower Ecc and myocardial torsion at rest and lower Ecc measured with dobutamine stimulation using Circle as compared to TomTec. Third, averaging of the results of repeated analyses increases both intervendor agreement and intravendor reproducibility; however the benefit is relatively low, considering that doubling or tripling of analysis times would be required. Lastly, although both software types show acceptable intravendor reproducibility, it is important to note that the Circle software shows slightly more variability for Ecc and myocardial torsion as compared to TomTec. Conversely, TomTec shows slightly more variability for Err measurements compared to Circle.Since the introduction of CMR-FT in 2009,Myocardial torsion and Err were subject to higher intervendor variability compared to Ecc and to lower bias between vendors. Although Err showed no significant bias between vendors, there was significant underestimation of torsion at rest, but not during dobutamine stimulation using Circle. The variability associated with torsion may well be explained by the fact that the methodology that has been validated with TomTec makes use of linear interpolation and standardized measurements at predefined anatomical LV locations as compared to Circle that derives rotational mechanics directly from the analysed sections.It is important to note that Ecc and myocardial torsion reached slightly higher intravendor reproducibility with TomTec as compared to Circle. This may be related to the fact that TomTec has been around for several years and been subjected to changes of the tracking algorithm several times (last change in December 2012); however, Circle showed better reproducibility for Err than TomTec.Considering these results, further refinements in the performance and subsequent increases in agreement between vendors and within vendors seem highly desirable. To achieve this, the impact of repeated measurements and subsequent averaging of results was tested. Although each of the parameters shows somewhat improved intervendor agreement and intravendor reproducibility with repeated analysis runs, this effect is most evident for myocardial torsion  deformations and strains.Significantly lower Ecc and resting torsion was found using Circle; however, the sample size of the current study in healthy volunteers is small and needs to be recognised when interpreting the results of the current study. The study did not include patients; however, similar CMR-FT reproducibility between health and disease had been reported beforeFurthermore myocardial tagging or speckle tracking echocardiography was not included as an independent reference standard. Notwithstanding this fact, it is important to note that TomTec has been compared to myocardial tagging with excellent agreementsGlobal deformation parameters were studied in the present study. Ideally, quantitative tools should be used to derive segmental information in addition to global values. Several studies have shown that segmental analysis does not provide high amounts of reproducibility for myocardial strain within repeated analysesIn conclusion, assessment of myocardial strain and torsion is feasible with the two types of commercially available CMR-FT software with reliable detection of increased myocardial deformation with dobutamine stimulation; however, myocardial strain and torsion measurements using both software types are subject to considerable inter and intravendor variability, even when averaging three analysis repetitions. It is important to note that Ecc and resting torsion values obtained from the Circle software are significantly lower as compared to TomTec. For both vendors, Ecc qualifies as the most robust parameter with the lowest variability. Whether or not the widespread availability of CMR-FT software types will allow the methodology to develop into a useful routine clinical tool has yet to be demonstrated.


In the last 20 years, nonalcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease worldwide, primarily as a result of the epidemic of obesity. NAFLD is strongly associated with insulin resistance, glucose intolerance, and dyslipidemia and is currently regarded as the liver manifestation of the metabolic syndrome, a highly atherogenic condition even at a very early age. Patients with NAFLD including pediatric subjects have a higher prevalence of subclinical atherosclerosis, as shown by impaired flow-mediated vasodilation, increased carotid artery intima-media thickness, and arterial stiffness, which are independent of obesity and other established risk factors. More recent work has identified NAFLD as a risk factor not only for premature coronary heart disease and cardiovascular events, but also for early subclinical abnormalities in myocardial structure and function. Thus, we conducted a systematic review and meta-analysis to test the hypothesis that NAFLD is associated with evidence of subclinical cardiac structural and functional abnormalities. In the last 20 years, nonalcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease worldwide, primarily as a result of the epidemic of obesity –4. NAFLDA systematic literature search was conducted by two researchers (LP and CA) to identify all articles (published from January 2000 to September 2014) that assessed by echocardiography cardiac geometry and function in NAFLD patients. We performed the search in Medline, EMBASE, and the Cochrane Library. Search terms were NAFLD OR NASH OR nonalcoholic fatty liver disease OR nonalcoholic steatohepatitis OR fatty liver OR liver fat OR steatosis OR liver enzymes OR transaminase OR ALT OR AST OR GGT OR severity of liver disease AND left ventricle OR left ventricular hypertrophy OR cardiac hypertrophy OR cardiac dysfunction OR ventricular dysfunction OR echocardiography. Search results were limited to English language publications. References of included articles were manually searched for other relevant studies.Inclusion criteria were observational studies including quantitative data on LV structure and/or function assessed by echocardiography and NAFLD diagnosed by (1) liver histology, (2) imaging , or spectroscopy (MRS)), or (3) biochemistry , or gamma-glutamyl transferase). Competing causes of steatosis, including alcohol consumption and viral, autoimmune, and metabolic hepatitis, had to be excluded. Only the updated or largest report was considered when multiple publications by the same research group were found.Data extraction was performed independently by two authors (EB and LP) and included title, authors, date of publication, study design, inclusion and exclusion criteria used in the study, number of patients and controls, the diagnostic procedures for NAFLD, the echocardiographic methods, and LV structural and functional measures. All quantitative echocardiographic variables had to be expressed as means ± SD; otherwise SE or 95% confidence intervals (CI) were used to estimate the SD.The quality of the selected studies was assessed independently by two authors (EB and CC) using the Newcastle-Ottawa Scale (NOS) for cohort and cross-sectional studies. The NOS uses a “star” rating system to judge quality based on three aspects of the study: selection of study groups, comparability of study groups, and ascertainment of either the exposure or outcome of interest . Any disE)/late mitral velocity (A) ratio, and E/early diastolic tissue velocity (e′) ratio. We used the standardized difference, which is the mean difference (between cases and controls) divided by the common within-group standard deviation for cardiac parameters. We chose the standardized mean difference as a measure of association instead of the weighted mean difference since the outcome variables had been determined by different instruments. Fixed or random-effect models were used to summarize results. The standardized differences were evaluated using the Der-Simonian and Laird procedures. In this analysis, the variation among studies is incorporated and thus the overall outcome estimates have greater standard errors. The Der-Simonian and Laird method uses weights equal to the reciprocal of the variance of the individual outcome estimates and thus takes account of the variation between them. Heterogeneity was estimated using the I2 index. If the I2 value was <50%, a fixed-effect meta-analysis was applied. If the I2 value was ≥50%, a random-effect meta-analysis was used.We calculated effect size for the following measures of LV structure and function: LV mass index, early mitral velocity .Publication bias was checked visually by creating a funnel plot with the standard error plotted against the mean difference of single LV parameters. In addition, publication bias was statistically tested by Egger's test. Consistent with recommendations to determine stability in the meta-analytic results, we computed the classic fail-safe analysis . This teThe first literature search identified 461 papers; 22 of these were potentially eligible for the analysis, but only 9 studies, six involving adults , 30–33 aNAFLD was defined by liver histology in one study, by ultrasound in four studies, and by computed tomography scan in one study. Three studies enrolled exclusively nondiabetic, normotensive individuals, one study enrolled type 2 diabetic patients, and one study enrolled never-treated essential hypertensive patients. The population-based study included patients with NAFLD and MetS.NAFLD was defined by ultrasound in one study, by ultrasound and elevated serum ALT in one study, and by MRI (and liver biopsy in a subgroup) in one study.2.7 or to body surface area (BSA), E/A ratio, the early annular diastolic tissue velocity (e′), and E/e′ ratio were the most frequently reported outcomes.The parameters reported across the selected publications varied among studies, but LV mass indexed to height2.7 [2.7 as well as those on LV mass indexed to BSA, the standardized difference in means was statistically significant (P < 0.0001) only for LV mass indexed to BSA    . E/e′ ra 0.0001) . Again, E/A ratio ; P = 0.72) and E/e′ ratio ; P = 0.44). The classic fail-safe N was relatively high to lower the significance of this meta-analysis .We found no evidence of publication bias based on Egger's test with respect to 2.7, the standardized mean difference in LV mass between obese children with NAFLD and obese subjects without liver involvement did not reach statistical significance (P = 0.069). In contrast, when compared to healthy lean controls, the standardized mean difference in LV mass was statistically significant ; P < 0.0001)  ; P = 0.72). Visual inspection of the funnel plot suggested the absence of publication bias for the E/e′ ratio, which was identified in 2 of the 3 eligible studies. However, the classic fail-safe N was relatively low when considering obese children with and without NAFLD, suggesting that only tenuous conclusions should be drawn.When pooling the data on LV mass indexed to height 0.0001) . In all e groups . However< 0.001) . In contWhile previous systematic reviews and meta-analyses have investigated the association between NAFLD and the risk of cardiovascular events , cerebrovascular disease , and peripheral vascular disease , or the E/A ratio and a higher E/e′ ratio, while children with NAFLD had higher E/e′ ratio.We found that NAFLD patients both adults and children have increased features of diastolic LV dysfunction. In fact, NAFLD adult patients had a lower E/A ratio is used as an estimate of the relaxation pattern of the ventricle. Furthermore, TDI can be used to measure myocardial motion, specifically the rate at which the mitral annulus moves toward the base during early diastole (e′). The LV filling pressures can be estimated by the E/e′ ratio [E/A ratio and E/e′ ratio are reliable markers of LV diastolic function.Diastolic LV dysfunction is increasingly acknowledged as a major contributor to the development of heart failure, but as the early onset of heart failure with preserved systolic function  is asymptomatic, it is often not diagnosed in the early stages . Althouge′ ratio . Thus E/In addition to LV diastolic dysfunction, our meta-analysis showed significant differences in LV mass index, a continuous measure of cardiac structure, between adult patients with NAFLD and controls. In the pediatric population, the standardized mean difference in LV mass between obese children with NAFLD and obese subjects without liver involvement did not reach statistical significance. However, when compared to healthy lean controls, the standardized mean difference in LV mass was statistically significant. Although LV diastolic dysfunction is known to be associated with the development of LV hypertrophy, investigations in both human and animal models of hypertension suggest that early LV diastolic dysfunction may precede the development of LV hypertrophy .It should be pointed out that, in a meta-analysis, the presence of heterogeneity in study design and clinical characteristics of subjects may influence the interpretation of the pooled risk estimates. However, even using the random-effects model, taking account of the variation between the different studies yielded a statistically significant estimate of LV dysfunction. Of note, there was no evidence of statistically significant heterogeneity among the studies involving children.The severity of liver disease was not considered in most of the studies. This may be due to liver biopsy being invasive and expensive and the ever present possibility of complications. Only one study in adults and one in children disclosed cardiac data according to liver histology and showed conflicting results. Karabay et al.  found no1H-MRS, Rijzewijk et al. showed that the intramyocardial fat content was significantly higher in uncomplicated type 2 diabetic men than in nondiabetic controls and was related to impaired cardiac metabolism [31P-MRS showed that patients with fatty liver had increased epicardial fat and abnormal cardiac metabolism [Although the pathogenesis of cardiac dysfunction in NAFLD is still unclear, insulin resistance, abnormal lipid profile, and low-grade inflammatory state have been suggested to play a role –47. Hepatabolism . Epicardtabolism , 51. Itstabolism . Perseghtabolism . Thus, etabolism , 52, leatabolism .α, and other proinflammatory cytokines) [More recently, it has been shown that the liver activates homeostatic mechanisms which increase the production and export of non-HDL-C to reduce the toxic effect of excess cholesterol due to diet. Thus, the liver may limit free cholesterol toxicity, but a consequence is that APOB-containing atherogenic lipoproteins are produced, which may, at least in part, account for the increased cardiovascular risk in patients with NAFLD . Emergintokines) , 55.PNPLA3) gene has been associated not only with increased hepatic fat content and serum liver enzymes but also with increased risk of NASH and fibrosis progression [Genetic studies have highlighted several single nucleotide polymorphisms that may characterize patients with a high risk for NAFLD development and progression –60. In pgression , 58. Recgression , 60. Of gression . In addigression  found thIn conclusion, our analysis supports the association between NAFLD and subclinical cardiovascular changes. However, confirmation in large cross-sectional and less heterogeneous studies is needed. If LV dysfunction in NAFLD is confirmed, future research directions should include strategies and interventions to prevent cardiac disease progression in patients with NAFLD.


Skin cancer is the most common cancer type in the United States, affecting more than 3 million people nationally . Basal cThe initial presentation of BCC is generally a pigmented nodule on the head or neck. Risk factors for BCC include chronic sun exposure; fair complexion; male gender; history of nonmelanoma skin cancer; family history of skin cancer; history of chronic arsenic exposure; or chronic immunosuppression, such as in lymphoma, transplant, or HIV-positive patients .Topical agents such as imiquimod or fluorouracil (5-FU) can be used in low-risk superficial BCC . HoweverWith the approval of vismodegib (Erivedge), patients with metastatic or locally advanced BCC who are unable to undergo surgery now have a treatment alternative that may provide a beneficial outcome. Vismodegib is approved for metastatic BCC or locally advanced BCC that has recurred following surgery, or for those who are not candidates for surgery and who are not candidates for radiation therapy .Vismodegib, which exerts its effects on the hedgehog (Hh) pathway, was approved in January 2012 by the US Food and Drug Administration (FDA) for monotherapy in the treatment of unresectable/malignant and advanced BCC . This drThe role of hedgehog ligands and pathway stimulation in BCC is theorized to lie in the activation of a 12-transmembrane domain protein  that is usually present during the telophase of the cell cycle . This prVismodegib antagonizes smoothen by binding to and inhibiting its movement inside the cell while also preventing transmission of signals. By antagonizing smoothen, vismodegib is capable of preventing cell proliferation caused by either a genetic mutation or an environmentally induced factor. A potential downside to the mechanism of vismodegib is the possibility for resistance to occur further downstream from the SMO receptor .A total of 68 participants with refractory, locally advanced, or metastatic solid tumors, 33 of whom had advanced BCC, were enrolled in a phase I trial investigating the hedgehog pathway inhibitor vismodegib. The objectives consisted of determining tolerability and safety, identifying maximum dose, discovering dose-limiting toxicities, assessing pharmacokinetics, and determining a phase II dose and schedule regimen. All participants in the study were at least 18 years of age, with the median age being 54. Exclusions from the study included patients with conditions such as major organ dysfunction, prolonged QT interval, and active infection requiring IV antibiotics . VismodeTumor assessment was performed via radiologic testing or physical examination to evaluate response rate. Disappearance of the tumor observed by physical exam was labeled as a complete response, and decrease in 50% or more of the tumor was considered a partial response. Of the 33 patients with BCC, 17 experienced a partial response, 2 experienced a complete response, 10 exhibited stable disease, and 4 showed signs of disease progression . Due to p = .001). An even greater response was seen in patients suffering from advanced BCC: 43%  with 13 complete responses  guidelines, version 1.0. Vismodegib proved to decrease cancerous lesions by 30% in the participants suffering from metastatic BCC  guidelines addressing BCC (version 2.2013) recommend vismodegib as an alternate therapy for those who have failed or have been unable to try other options . The appVismodegib is provided as a 150-mg capsule intended to be taken by mouth once daily. It may be taken without regard to meals but should not be split, opened, or altered in any way prior to administration. Vismodegib has a pregnancy category D rating and is not indicated for use during pregnancy because its mechanism of action may result in serious fetal harm. Pediatric indications for vismodegib do not exist, and due to adverse effects on developing bone growth, use in the pediatric population is not recommended. Vismodegib has not been tested in patients with renal and/or hepatic deficiencies, rendering dosage information unavailable for these populations. Since vismodegib is a minor substrate of p-glycoprotein as well as cytochrome P450 3A4 and 2C9 isoenzymes, careful monitoring of therapeutic effect should be considered if the concurrent use of inducers or inhibitors of these enzymes is required .Treatment options for those with metastatic and advanced BCC unable to undergo surgery are limited. The NCCN has updated the BCC guidelines to include vismodegib as an option for high-risk patients who have exhausted other options. Although vismodegib produced many side effects in its clinical trials, reduction in tumor size and potential for complete response make it an attractive therapy option for those ineligible for surgery. Vismodegib is breaking down barriers in BCC and has the potential to leave its imprint on the world of oncology while paving the way for drugs with a similar mechanism of action.


Cardiotoxicity is a major limiting factor preventing dose-effective use of multiple cytotoxic agents in cancer treatment. Current cardiotoxicity diagnosis is based on functional changes that occur late in the course of the disease. In this pre-clinical pilot study, we hypothesize myocardial T1 and T2 mapping will identify mice at risk of death secondary to doxorubicin-induced cardiotoxicity prior to cardiac function deterioration.o, 6o, 10o, 16o, and 25o) was used for T1 mapping and a spin-echo sequence with varied echo times  was used for T2 mapping. Average myocardial T1 and T2 relaxation times and ejection fraction were compared between mice that died during treatment, survived to the end of treatment, and controls using repeated measure linear modeling.Eleven healthy, 10-week-old C57BL/6 female mice were included in the study. All procedures are in accordance with an Institutional Animal Care and Use Committee approved protocol. Doxorubicin-induced cardiotoxicity was generated by giving 8 mg/kg of doxorubicin via intraperitoneal (IP) injection weekly for 4 weeks in n = 8 randomly selected mice. A control group of n = 3 mice was given a weekly volume equivalent dose of IP normal saline. Each mouse underwent ECG-gated CMR on a 7T small animal scanner  prior to treatment, at 2 weeks, and post-treatment. Steady-state free precession images were acquired at the left ventricular base, mid-ventricle, and apex and ejection fraction (EF) was calculated . T1 . and EF  did not demonstrate a significant relationship. There was a non-significant trend of increased pre-treatment myocardial T1  and T2  in mice who died compared to those who survived. EF doesn't show the same trend (58 ± 7% vs. 56 ± 5%). (Figure Average myocardial T2 in mice undergoing IP chemotherapy was significantly correlated with outcome, while T1 and EF showed no correlation. The trends identified in this pre-clinical pilot study further drive the hypothesis that myocardial tissue characterization may be an effective tool for diagnosis and risk-stratification of chemotherapy-induce cardiotoxicity.Northwestern CTI Pilot Grant, NIH/NCI R25 CA 132822.


Considering allpatients, the V2 transition ratio had the highest sensitivity (92.3%),while the R wave duration and R/S wave amplitude indices in V2 had thehighest specificity (93.9%). The latter finding had a maximal area under the ROCcurve of 0.925. In patients with left ventricular (LV) rotation, the V2transition ratio had the highest sensitivity (94.1%), while the R wave duration andR/S wave amplitude indices in V2 had the highest specificity (87.5%). Theformer finding had a maximal area under the ROC curve of 0.892. All three publishedECG algorithms are effective in differentiating the origin of OTVAs, while theV2 transition ratio, and the V2 R wave duration and R/S waveamplitude indices are the most sensitive and specific algorithms, respectively.Amongst all of the patients, the V2 R wave duration and R/S wave amplitudealgorithm had the maximal area under the ROC curve, but in patients with LV rotationthe V2 transition ratio algorithm had the maximum area under the ROCcurve.Our objective is to evaluate the accuracy of three algorithms in differentiating theorigins of outflow tract ventricular arrhythmias (OTVAs). This study involved 110consecutive patients with OTVAs for whom a standard 12-lead surface electrocardiogram(ECG) showed typical left bundle branch block morphology with an inferior axis. Allthe ECG tracings were retrospectively analyzed using the following three recentlypublished ECG algorithms:  The outflow tract ventricular arrhythmia (OTVA) is a common medical condition, andapproximately 80% of cases originate from the right ventricular outflow tract (RVOT). There aOne hundred and ten  consecutive patients  with PVCs or ventricular tachycardia (VT) who underwent successfulablation at one of the three Third-Class-A Hospitals of the study were enrolled. Allthe ablation targets were located in the outflow tract, and patients who underwentsuccessful ablation via large veins were excluded. One patient failed two RFtreatments due to PVCs. Standard 12-lead ECGs were obtained from all patients undersinus rhythm (SR) and OTVA conditions. All the OTVA ECGs showed a typical left bundlebranch block morphology with an inferior axis. Holter monitoring revealed 10,000monomorphic PVCs/24 h or PVC loads ≥10%. Structural heart diseases were excluded byechocardiography, cardiovascular CT, or coronary angiography (for some patients).Patients discontinued anti-arrhythmic drugs (AADs) for at least five half-livespre-operatively. All patients signed informed consents pre-operatively. Of the 110patients, 84 (76.4%) underwent RF ablation targeted at the RVOT via the femoralvenous approach, and 26 (23.6%) had RF ablations targeted at the aortic sinus cusp(ASC) via the femoral arterial approach.All procedures and protocols were approved by the Institutional Beijing Chao-YangHospital Ethics Committee, Capital Medical University, Beijing, China.¯ Measure, Germany)was used to measure the values of QRS waves under SR and OTVA conditions on the sameECG; for monomorphic PVCs, only the first QRS was measured. The following 3 indiceswere sequentially calculated.During OTVA conditions, all standard 12-lead surface ECGs showed complete left bundlebranch block with an inferior axis. Software  index (Z) index . The cheV2transition ratio (OTVA-to-(R/R+S)SR ratio ≥0.5,while an RVOT origin is suggested by a (R/R+S)OTVA-to-(R/R+S)SRratio <0.5.on ratio . An ASCV2R wave duration and R/S wave amplitude indices (1 or V2 lead in relation to the entire QRS wave duration(R/QRS). An ASC origin is indicated if the R/QRS wave duration ratio is ≥50%. The R/Swave amplitude refers to the R/S wave amplitude ratio. An ASC origin is indicated ifthe R/S ratio is ≥30%  was placed at the rightventricular outflow tract, adopting activation mapping and pace mapping to determinethe ablation target. If an ideal target was not pursued in the right ventricleanother catheter was inserted via the right femoral artery mapping at the leftventricular outflow tract. The ablation settings were as follows: power of 20-25 W,upper temperature limit of 43°C, perfusion flow rate of 30-50 mL/h, and dischargeduration of 30-60 s. No thromboses or hemorrhage occurred during a singleprocedure.The criterion for immediate success after RF ablation was the absence of PVCs or theabsence of PVC symptoms observed 30 min after intravenous infusion ofisoproterenol.The criterion for long-term success was absence of clinical episodes of ventriculararrhythmias during a 1-year follow-up .SPSS18.0  and STATA11.0  were used for statisticalanalyses. Data are reported as means±SD. The sensitivity, specificity, positivepredictive value, and negative predictive value of each indicator were calculatedusing the Fisher's exact test with a 4-fold table. The receiver operatingcharacteristic (ROC) curve analysis was used to assess the three algorithms.P<0.05 indicated statistical significance.Of the 84 RVOT cases, 72 (86%) were RF ablations that targeted the septum and 12 (14%)targeted the free way. Of the 26 ASC cases, 1 (4%) was a RF ablation that targeted theright coronary sinus, 22 (88%) targeted the left coronary sinus, and 2 (8%) targeted theregion between the two sinuses.No significant differences were detected with respect to the clinical information of thepatients with RVOT and ASC origins, including gender, age, PVC load, left ventricularend-systolic and end-diastolic diameters, wall thickness, and left ventricular ejectionfraction . There w2transition ratio, and V2 R wave duration and R/S wave amplitude indices ofthe two groups; no significant differences were found in the SR TZ score, V2R wave amplitude, and PVC QRS duration.The ECG characteristics of the patients are shown in 2 transition ratio had the highest sensitivity . The latterfinding had a maximal AUC of 0.925 (2 transition ratio (0.91) and the TZ index (0.84)(P<0.01).The Vy 92.3%; , while tof 0.925 ,followe2 transition ratio had the highestsensitivity . The former finding had a maximal AUC of 0.892 (2 R wave duration and R/S waveamplitude indices (0.865) and TZ index (0.781) (P>0.05).In patients with LV rotation, the Vy 94.1%; , while tof 0.892 , followe2 transitionratio and TZ index. A comparison between these two algorithms and the previousapproaches has not been reported, which served as the basis for conducting the currentstudy. Of the three algorithms, the V2 transition ratio had the highestsensitivity, while the R wave duration and R/S wave amplitude indices in V2had the highest specificity. Analyses of the AUC of the 3 algorithms, which takessensitivity and specificity into account, were all between 0.7 and 0.9; therefore, all 3algorithms seem to be reliable approaches to differentiating the origins of OTVAs. Inspite of the presence or absence of cardiac rotation, no significant differences existedin AUCs of the V2 transition ratio and V2 R wave duration and R/Swave amplitude indices, which indicated that these two algorithms had similar diagnosticvalues in OTVAs. The TZ index had a diagnostic value similar to the V2transition ratio in patients with rotation.Several reports have focused on differentiating the origins of PVCs with pre-operativeECGs and some reports have proposed systematic procedures for demonstrating this process-11. ROf the 3 algorithms, the TZ index was slightly inferior. Because the score wascalculated at an advancement of 0.5, subtle differences among the leads might beneglected. It is possible that there were 2 leads whose R/S wave ratios were between 0.9and 1.1 simultaneously, making it difficult to determine the score and thereforeaffecting the accuracy of target positioning. As a commonly observed phenomenon in aclinical ECG, cardiac rotation is affected by many factors . Sengupt2 transition ratio had the highest sensitivity, while the Rwave duration and R/S wave amplitude indices in V2 had the highestspecificity. No significant differences were found in AUCs of the two algorithms, whichindicates similar diagnostic values in differentiating the origins of OTVAs, while theTZ index was slightly inferior. No significant differences in diagnostic values werefound among the three algorithms for patients with rotations in the precordial leads.These algorithms are currently used in clinical practice, each with its own advantages.Applying two or three methods to define the OTVAs origin with mutual verification maythus be recommended.In summary, our study showed that, in spite of the presence or absence of cardiacrotation, the V2lead was chosen because this position is relatively reliable. This retrospective studyhas verified the accuracy of different algorithms used in identifying the origins ofOTVAs, through follow-up evaluations. Although being one of the studies with the largestsample size to date, a prospective study should be conducted for verification.A shortcoming of this research was that the data were collected from three hospitals.Therefore, the lead positions of the ECGs might have been different. The V


The treatment of microcirculatory impairment will have great impact if it can be applied to myocardial infarction (MI) patients. The problem is how to study these tiny structures and microphenomenon in heart.We investigated the visualization of cardiac microvessels embolization by the mean of X-ray phase contrast imaging (XPCI), which is a recently emerged imaging technique. Using the information of X-ray phase shift, it is sensitive to weak absorbing materials. Two MI SD rats were used as the microvessel embolization samples. MI was surgically induced by ligating left anterior descending artery. Imaging was performed 24 hours post-infarct, with barium sulfate as contrast agent.The coronary arteries were visualized with smooth walls and clear edges. The ligated vessels, with the diameter of about three hundred microns, can be clearly distinguished and there were no distal blood flow downstream from these branches. The results indicate that phase contrast imaging can directly demonstrate the distribution of microvessels, and estimate the area of MI. The infarct location was in good agreement with pathological analyses of the models.The advantage of our method is directly observing and evaluating microvessel embolization which simplifies the procedure of diagnoses. Moreover, it is helpful for predicting the prognosis in MI and judging if angiogenesis happens. The occlusion of coronary artery is the most common cause of Myocardial Infarction (MI) . When MIClinically, reperfusion has proven to be the vital procedure to improve the survival rate of MI patients. Recent studies have shown that even though after a rapid reopening of the previously obstructed coronary artery, some distal microvessels remain ischemia, which is called no-reflow phenomenon ,4. This With the development of imaging technique, contrast echocardiography (MCE), positron emission tomography (PET), and contrast-enhanced magnetic resonance imaging (MRI) are becoming the most effective method for microvascular assessment. The area of ischemia can be defined through those methods. But the use of these techniques have been limited on imaging individual microvessels -9. For tX-ray Phase contrast imaing (XPCI) became a research focus about some decades ago with the awareness of its high spatial resolution and contrast on imaging soft tissues ,12. It iIn order to observe blood vessels, contrast agents are widely used in conventional X-ray examination, including Digital subtraction angiography (DSA), Computed tomography angiography (CTA) and enhanced CT scanning. Though PCI can provide high contrast of soft tissues, we used contrast agent in our experiments to highlight microvessels in rat hearts. In this way, the image will compose more details of vessel networks due to phase contrast. Moreover, other soft tissues such us cardiac valves and myocardium can also be detected in the same image.Accordingly, in this paper, we sort to directly visualize coronary microvessels, micro embolization and evaluate myocardial ischemia area by means of phase contrast imaging.All experiments and procedures carried out on the animals were approved by the animal welfare committee of Capital Medical University and the approval ID is 0000259. Two adult normal SD rats, approximately 250 g of body weight each, were anesthetized by an intraperitoneal injection of chloral hydrate 4.5 ml/kg, tracheal intubated and connected to a small animal ventilator. MI was induced by ligating of the left anterior descending (LAD) coronary artery with a 6 absorbable suture through the left fourth intercostal space. Then we closed the thoracic cavity layer by layer and removed the endotracheal tube.In order to observe the micro vascular network, contrast agent was used. But, in our experiment, the particles of contrast agent should be smaller than the capillaries. At the same time, the agent cannot migrate through the walls of the vessels. Moreover, it should be insoluble even though the tissue was fixed in formalin. After a serious of test, barium sulfate is proven to be the desirable one. To ensure microvessels angiography, it should be ground into very fine particles prior to use.24 h after the operation, we anaesthetized the rats again, opened their thoracic cavity to expose the heart, cut the postcava, ligated the ascending aorta, and then injected the barium sulfate solution (20% v/v) by a scalp acupuncture, which connected to a 20 ml syringe, via the aorta root. After the coronary artery turned white, we harvested the hearts and quickly preserved them in formalin solution. Finally, phase contrast imaging was performed on these isolated hearts. After imaging, every heart was equally dissected into four blocks along the long axis of heart and paraffin embedded. 5 μm thick sections were cut and stained with hematoxylin and eosin (H&E).The coronary microvessels were visualized by X-ray phase contrast imaging. The principle of XPCI is Fresnel diffraction theory . ContrasThe imaging experiment was performed in Shanghai Synchrotron radiation facility BL13W beamline. Briefly, it consists of one double-crystal monochromator, one rotation sample stage and one CCD detector (Figure For 2D imaging, the CCD detector we chosen had a resolution of 2048 × 2048 pixels with 3.7 μm × 3.7 μm each. The distance between sample and detector was 0.28 m. The explore time was 3.5 s. For CT experiment, the resolution of the detector was 4008 × 2672 pixels with 9 μm × 9 μm each. After the sample stage rotated for 180 degree, 1254 projection images were obtained, with an exposure time of 90 milliseconds each. The distance between sample and detector was 0.52 m. The surface dose was about 2.66 mGy for each projection. Filtered back projection method was used to reconstruct the cross-section of the sample [The two rats were established as models of acute myocardial infarction. 24 h after infarction, we started the imaging test. The phase contrast image of the heart is shown in Figure Totally, we got 1677 phase contrast imaging slices. From the 3D rendered heart, the tree-like coronary arteries and the distal small arteries up to tenth level with a diameter of 15 μm were clearly visualized (Figure Our present study demonstrated that microvessel embolism is detectable and visible in myocardial infarction by phase contrast imaging. By assessing the no-blood-flow vessel, we have speculated the infarction area.For myocardial infarction imaging, there are a couple of methods. CTA is widely used in clinic to evaluate coronary arteries diseases; DSA is currently considered as the diagnostic standard. Other modalities such as contrast enhanced MR, PET, and ultrasound are becoming the effective methods for infarction imaging ,19,20. IIn the study of coronary heart disease, it is very important to directly observe the anatomic variations and anastomosis of microvessels. Thus, we imaged the whole rat hearts. Microvessels, such as coronary artery and some other arteries and veins were shown in our results. The infarct vessel can be directly found in the 3D vessel tree. For the part without vessel supply, we predict it as the ischemia area. The results were highly consistent with the histological section which is recognized as the accurate view of specimens.The contrast agent we used in our experiment was barium sulfate. It can deposit in the vessel even after the heart is fixed in formalin solution. The histological result also proved this: the vessel lumen was completely filled with gray color contrast agent. The shortcoming is that the blood flow was solidified too fast in microvessels before barium sulfate contrast agent enter into them. The reason to choose barium sulfate lies in our in vitro heart imaging experiment. If we can image the heart in vivo, then clinical soluble contrast agent can be used. However, the most important problem to apply XPCI to in vivo heart imaging is the imaging speed. It is possible for 2D continuous heart imaging by XPCI. But for 3D imaging, the fast heart beating is still a big problem. Even some tiny movement will cause blur in 3D reconstruction of microvessels. In our opinion, the possible solution may be new high speed CCD and rotation stage.In conclusion, by using XPCI, it is possible to directly image microvessels in MI model and quantify the infarct microvessels. The quantitative character of the microvessels can be directly observed. The microvessel stenosis strongly correlates with clinical no-reflow phenomenon. Phase contrast imaging may become a new way to study MI. In the next step, we will explore the clinical significance of our findings, especially in no-reflow phenomenon.The authors declare that no competing interests exist.LZ contributed to the XPCI data acquisition, image processing and manuscript drafting. KW and FZ established the MI rats model. XL is responsible for histological testing. SL participated in the design and supervised the experiment. All authors read and approved the final manuscript.


Measurement of myocardial T2* is becoming widely used in the assessment of patients at risk for cardiac iron overload. The conventional breath-hold, ECG-triggered, segmented, multi-echo gradient echo (MGRE) sequence used for myocardial T2* quantification is very sensitive to respiratory motion and may not be feasible in patients who are unable to breath-hold. We propose a free-breathing myocardial T2* mapping approach that combines a single-shot gradient-echo echo-planar imaging (GRE-EPI) sequence for T2*-weighted image acquisition with automatic non-rigid motion correction (MOCO) of respiratory motion between single-shot images.ECG-triggered T2*-weighted images at different echo times were acquired by a black-blood, single-shot GRE-EPI sequence during free-breathing. A single image at a single TE is acquired in each heartbeat. Automatic non-rigid MOCO was applied to correct for in-plane respiratory motion before pixel-wise T2* mapping. In a total of 117 patients referred for clinical cardiac magnetic resonance exams, the free-breathing MOCO GRE-EPI sequence was compared to the breath-hold segmented MGRE approach. Image quality was scored independently by 2 experienced observers blinded to the particular image acquisition strategy. T2* measurements in the interventricular septum and in the liver were compared for the two methods in all cases with adequate image quality.T2* maps were acquired in all 117 patients using the breath-hold MGRE and the free-breathing MOCO GRE-EPI approaches, including 8 patients with myocardial iron overload and 25 patients with hepatic iron overload. The mean image quality of the free-breathing MOCO GRE-EPI images was scored significantly higher than that of the breath-hold MGRE images by both reviewers. Out of the 117 studies, 21 breath-hold MGRE studies  were scored to be less than adequate or very poor by both reviewers, while only 2 free-breathing MOCO GRE-EPI studies were scored to be less than adequate image quality. In a comparative evaluation of the images with at least adequate quality, the intra-class correlation coefficients for myocardial and liver T2* were 0.868 and 0.986 respectively (p < 0.001), indicating that the T2* measured by breath-hold MGRE and free-breathing MOCO GRE-EPI were in close agreement. The coefficient of variation between the breath-hold and free-breathing approaches for myocardial and liver T2* were 9.88 % and 9.38 % respectively. Bland-Altman plots demonstrated good absolute agreement of T2* in the interventricular septum and the liver from the free-breathing and breath-hold approaches .The free-breathing approach described for T2* mapping using MOCO GRE-EPI enables accurate myocardial and liver T2* measurements and is insensitive to respiratory motion. Cardiac failure and arrhythmia induced by myocardial iron overload is the leading cause of death in thalassemia major patients and in other patients who receive chronic blood transfusions , 2. SincConventionally, T2* in the heart is measured in a region of interest (ROI) manually delineated in the interventricular septum to avoid the susceptibility gradients that can be severe in other segments of the left ventricular myocardium. The mean pixel value within the septal ROI of each T2*-weighted image is calculated, and then a mono-exponential decay curve is fit to these mean values across the multiple TE images. Pixel-wise T2* mapping is another approach that is gaining popularity based on the recent success of similar approaches to myocardial T1 mapping and T2 mapping. Pixel-wise mapping involves curve fitting on individual pixels; while this process is more prone to noise than ROI fitting, it can be totally automated and recent studies comparing region-based and pixel-wise methods for cardiac T2* quantification have demonstrated that pixel-wise T2* mapping reduces inter- and intra-observer variability .A breath-hold, ECG-triggered, segmented, multi-echo gradient echo (MGRE) sequence is commonly used to acquire the series of images at multiple echo times needed to quantify myocardial T2* –8, 11. AFree-breathing methods for myocardial relaxation parameter mapping have been previously described using the combination of single-shot image acquisition and non-rigid motion correction (MOCO). Single-shot image acquisition, which acquires an entire image within one heartbeat, is inherently less sensitive to artifacts from respiratory and cardiac motion, while non-rigid MOCO ensures proper alignment of images from different respiratory positions to enable signal averaging and pixel-wise curve fitting. These methods have been successfully applied in myocardial T1 , 15 and In this work, we propose a different approach for free-breathing myocardial T2* mapping using a single-shot gradient-echo echo-planar imaging (GRE-EPI) sequence for T2*-weighted image acquisition, and automatic non-rigid MOCO tailored for myocardial T2* mapping. A single image at a single TE is acquired in each heartbeat, using a segmented EPI readout to greatly accelerate each T2*-weighted image acquisition, therefore reducing the potential sensitivity to cardiac and respiratory motion artifact. Furthermore, because each T2*-weighted image at each different echo time is acquired independently in a single heart beat; the choice of echo times used in the curve fitting is more flexible than in the multi-echo GRE approach; i.e., the TEs are not restricted by echo spacing. We compared myocardial and hepatic T2* measurements using free-breathing GRE-EPI and breath-hold MGRE approaches in a cohort of patients referred for clinical CMR in two different imaging centers, The Ohio State University Richard M. Ross Heart Hospital (OSU) in Columbus, OH and The Royal Brompton Hospital (RBH) in London, England. We hypothesize that the combination of single-shot GRE-EPI and motion correction will enable free-breathing myocardial T2* mapping with results comparable to the standard, breath-hold, MGRE, segmented k-space technique.A black-blood, single-shot GRE-EPI sequence Fig. . was devA breath-hold, ECG-triggered, black-blood, segmented MGRE sequence with gradient fly-back for mono-polar readout was used as the reference standard. In every TR, eight echoes were acquired to form eight T2*-weighted images, each at a different echo time. Seven to nine k-space lines (segments) were acquired in each cardiac cycle, resulting in a typical scan time of ten to thirteen heartbeats. Two different imaging matrix sizes were used depending on the site where the data were acquired. The detailed imaging protocols are listed in Table Free-breathing, T2*-weighted images from the ECG-triggered, dark-blood, single-shot GRE-EPI sequence were motion corrected using automatic non-rigid image registration  to correi) = S(0) exp(-TEi/T2*), where S(TEi) is the signal intensity at the ith echo and TEi is the echo time. A robust iteratively re-weighted fitting was used [To remove noise regions (air in the lungs and outside of the body) in the T2* maps, an automatic binary mask was generated based on the maximum intensity projection across the images at different TEs using the iterative Otsu threshold ; this tewas used , 29, in Imaging was performed on two identical 1.5 T clinical scanners , with maximum gradient amplitude of 45 mT/m, and maximum slew rate of 200 mT/m/ms. Body matrix array and spinal array coils were used for signal reception.A total of 117 patients  47.7 ± 17.1 years, ranging from 9 to 82, referred for clinical CMR exams that included evaluation of myocardial T2* were studied to evaluate the effectiveness of this new technique and to compare image quality and quantitative T2* results with the standard, segmented k-space method. Eighty-eight of the patients were referred for evaluation of cardiomyopathy and were imaged at OSU. Twenty-nine patients with known thalassemia referred to CMR specifically for evaluation of myocardial and hepatic iron were imaged at RBH. All patients underwent T2* imaging using both the conventional segmented MGRE sequence during breath-hold, and the new MOCO GRE-EPI sequence during free-breathing. Identical scan parameters were used for the MOCO GRE-EPI sequence at both centers. The breath-hold MGRE protocol used at RBH had a somewhat higher image matrix than the protocol used at OSU (256 × 84 vs. 160 x 90); this minor difference only reflected the standard clinical scan parameters employed by each site. A single mid-ventricular short axis slice was acquired in all patients. The study was approved by the local Institutional Review Boards in both sites; informed consent was waived.Qualitative comparisons were made between the images acquired using the breath-hold MGRE and the free-breathing GRE-EPI sequences. For each acquisition strategy in each patient, the first 7 T2*-weighted images (with echo times ranging from 1.9 ms to 14 ms) were displayed on a single slide for the purpose of image quality scoring. The order of display was randomized with regard to both subject number and acquisition strategy. Image quality was scored independently by 2 experienced observers blinded to the particular image acquisition strategy. A 5-point scoring system was used to assess image quality based on artifact level: 1 - Very poor image quality with unusable images; 2 - Less than adequate image quality with substantial artifact; 3 - Adequate image quality with moderate artifact; 4 - Good image quality with minimal artifacts; 5 - Excellent image quality with no significant artifact. The image quality scores for the breath-hold and free-breathing techniques from the two reviewers were compared separately using the pairwise Wilcoxon signed rank test with a significance level of 0.05.t-test with significance level of 0.05.In only those cases in which both techniques were judged to have at least adequate image quality  by both reviewers, the mean T2* was measured in the interventricular septum and in the liver in each patient by manually drawing ROIs directly on the T2* maps. A comparison between the mean T2* values derived from the breath-hold and free-breathing approaches for both liver and myocardium in each patient was performed by calculating the intra-class correlation coefficient (ICC)  with twoCalibration curves relating liver T2* to liver iron content have been reported –33 and aT2* maps were acquired in all 117 patients using the breath-hold MGRE and the free-breathing MOCO GRE-EPI approaches. Eight patients presented myocardial iron overload, as determined by the standard MGRE technique. Myocardial overload was mild in 6 cases (14 ms ≤ T2* < 20 ms), moderate in 1 case  and severe in 1 case (T2* < 10 ms). Hepatic iron overload was present in 25 patients. Mild hepatic iron burden   was presFigure In the four patients with severe hepatic iron overload, both breath-hold and free-breathing techniques did not provide reliable T2* measurements in the liver. Figure p = 0.0101 and 0.0324 respectively). The average image quality scores from reviewer #1 were 3.34 ± 1.40 and 3.72 ± 0.71 for breath-hold MGRE and free-breathing MOCO GRE-EPI, respectively. The average quality scores from review #2 were 3.82 ± 1.31 and 4.10 ± 0.74 for breath-hold MGRE and free-breathing MOCO GRE-EPI, respectively. Both reviewers agreed that image quality was more variable in the T2*-weighted images acquired using breath-hold MGRE due to the low image quality that resulted from failed breath-hold in some patients. Out of the 117 studies, reviewer #1 scored the image quality of 21 breath-hold MGRE studies  to be below average or very poor ; while reviewer #2 scored 36 breath-hold MGRE studies  to be below average or very poor, including the same 21 patients as reviewer #1. Only 2 free-breathing MOCO GRE-EPI studies were scored to be less than adequate image quality, while the MGRE images of one patient were scored to be very poor image quality by both reviewers due to failed breath-hold.The mean image quality of the free-breathing MOCO GRE-EPI images was scored significantly higher than that of the breath-hold MGRE images by both reviewers (p < 0.001), indicating that the T2* measured by breath-hold MGRE and free-breathing MOCO GRE-EPI were very consistent. The CoVs between the breath-hold and free-breathing approaches for myocardial and hepatic T2* were 9.88 % and 9.38 % respectively. As demonstrated in the Bland-Altman plots shown in Fig. t-test showed that there were no significant differences between the breath-hold and free-breathing approaches in either myocardial or hepatic T2* (p = 0.937 and 0.598 respectively).The 37 patients whose image quality was scored as less than adequate image quality by at least one reviewer for either technique were excluded from the comparison of quantitative T2* results. Out of the 80 patients with adequate image quality from both breath-hold MGRE and free-breathing MOCO GRE-EPI techniques, 17 patients did not have a large enough homogeneous liver region within the ventricular short axis image to permit measurement. 4 patients had severe hepatic iron overload and both techniques failed to measure T2* in the liver. Thus, the T2* values measured in the interventricular septum and in the liver using both techniques were compared in 80 patients and 57 patients, respectively. The ICCs, for myocardial and hepatic T2*, were 0.868 and 0.986 respectively  without pushing the parallel acceleration beyond a factor of 2 thereby avoiding excessive g-factor SNR loss. This acquisition speed is fast enough to avoid respiratory induced artifacts, and motion correction is utilized to compensate for in-plane respiratory motion between images secondary to variable diaphragm positions during acquisition. Compared to the free-breathing T2* mapping technique recently described in , which uAutomatic non-rigid image registration was used to correct for in-plane respiratory motion. Clinical myocardial T2* maps are commonly acquired in the mid-ventricular short axis view in which it has been previously demonstrated that through-plane motion is not significant . Since oImage quality scoring was performed intentionally using the T2*-weighted source images rather than the resulting T2* maps. Motion ghosting and other artifacts tend to be more visible in the original T2*-weighted images and may not be as obvious in the T2* maps. For example, in Fig. An iterative robust fitting algorithm that reweighted the signal intensity at all TEs to reflect fidelity to mono-exponential decay was used to fit the T2* curves. Pixel-wise T2* estimation using this method has been previously compared with ROI-based T2* assessment using commercially available validated software . It was found that the mean T2* within the ROI of the interventricular septum was highly correlated with the ROI-based T2* estimation . Recentl0 field homogeneity is poor or there is excessive adipose tissue in the FOV. Advanced, volume selective shimming procedures may be applied to further improve B0 field homogeneity and reduce off-resonance artifacts from fat [The primary limitation of this study was that relatively few patients with significant myocardial iron overload were included. A larger systematic study will be necessary to compare and evaluate the performance of the conventional breath-hold and new free-breathing myocardial T2* mapping techniques in patients with low T2* in the heart. Regarding liver T2* it should be noted that both the breath-hold and free-breathing protocols failed to measure very short T2* (<1.8 ms) in patients with severe hepatic iron overload. In the breath-hold MGRE protocols used at the two test centers, the earliest echo time sampled was 1.6 or 1.9 ms and the echo spacing between TEs was 2.2 or 1.6 ms determining by the imaging matrix (256 vs. 160) and readout bandwidth (814Hz/Pixel). Due to the very fast T2* decay, as shown in Fig. from fat  or localWe have developed a technique for T2* mapping using MOCO GRE-EPI that enables accurate myocardial and hepatic T2* measurements and is insensitive to respiratory motion. The approach is fully automatic and could be especially beneficial for patients who are unable to breath-hold during the T2* exam.


Regular physical activity over a long time period leads to a cardiac adaptation described as "athlete's heart". The purpose of this study was to determine the effects of intensive daily training in a specific type of sports- professional soccer, in regard to morphological and functional left ventricular parameters assessed by cardiac magnetic resonance imaging (CMRI) and to compare these with non-athletic healthy volunteers.CMRI was performed in 17 male professional soccer players from the German Bundesliga team squad of the Hamburger SV and 8 age-, sex- and weight-matched untrained controls at 1.5 T  during the active season. For quantitative CMRI, an electrocardiographically triggered steady-state free precession (SSFP) cine sequence  was performed in short- and long-axis views. Quantitative analysis included end-diastolic (EDV) and end-systolic volumes (ESV), stroke volume (SV), left ventricular ejection-fraction (EF) as well as end-diastolic (EDMM) and end-systolic myocardial mass (ESMM). CMRI data were analyzed by two independent observers using the HeAT-Software. Data are given as the mean of both observers.P< 0.04), ESV  and LV mass . Stroke volume  and LV ejection fraction  were similar in both groups. The professional soccer players had a significantly lower resting heart rate than non-athletes .In professional soccer players a significant increase of the following parameters was determined compared to non-athletes: EDV (229 ±24 ml vs. 196 ±30 ml, Long-term training in professional soccer players is characterised by left ventricular adaptation leading to an increase in functional parameters and myocardial mass. CMRI allows an objective quantitative assessment and might help to differentiate physiologic cardiac adaptations from conditions such as hypertrophic cardiomyopathy.N/A.


Increased baseline heart rate is associated with cardiovascular risk and all-cause mortality in the general population. We hypothesized that elevated preoperative heart rate increases the risk of myocardial injury after non-cardiac surgery (MINS).We performed a secondary analysis of a prospective international cohort study of patients aged ≥45 yr undergoing non-cardiac surgery. Preoperative heart rate was defined as the last measurement before induction of anaesthesia. The sample was divided into deciles by heart rate. Multivariable logistic regression models were used to determine relationships between preoperative heart rate and MINS (determined by serum troponin concentration), myocardial infarction (MI), and death within 30 days of surgery. Separate models were used to test the relationship between these outcomes and predefined binary heart rate thresholds.−1) was independently associated with MINS {odds ratio (OR) 1.48 [1.23–1.77]; P<0.01}, MI , and mortality . The lowest decile (<60 beats min−1) was independently associated with reduced mortality , but not MINS or MI. The predefined binary thresholds were also associated with MINS, but more weakly than the highest heart rate decile.Patients with missing outcomes or heart rate data were excluded from respective analyses. Of 15 087 patients, 1197 (7.9%) sustained MINS, 454 of 16 007 patients (2.8%) sustained MI, and 315 of 16 037 patients (2.0%) died. The highest heart rate decile (>96 beats min−1 is associated with MINS, MI, and mortality after non-cardiac surgery. This association persists after accounting for potential confounding factors.Preoperative heart rate >96 beats minNCT00512109. Increased baseline heart rate is associated with cardiovascular morbidity and mortality in the general population, but its impact on perioperative outcomes is unclear.Secondary analysis of an international multicentre study of patients undergoing non-cardiac surgery was performed.−1 was associated with increased myocardial injury, myocardial infarction, and mortality.In this large prospective cohort study, heat rate >96 beats min12 Cardiovascular complications are a prominent cause of postoperative morbidity and mortality.3 Recent data suggest that one in 10 surgical patients experience postoperative myocardial injury attributable to ischaemia, characterized by a transient increase in the serum concentration of cardiac troponin, which is strongly associated with 30 day death.45 In contrast to other acute cardiac events, perioperative myocardial injury is predominantly asymptomatic, and in the absence of routine surveillance of troponin concentrations, four out of five instances are not identified.46 Conventional teaching suggests that tachycardia is an important causal factor for myocardial injury, as a result of myocardial oxygen supply–demand imbalance.78 Epidemiological data from the general population consistently demonstrate that resting heart rate is associated with cardiovascular risk and mortality.12 These relationships appear independent of underlying pathology or cardiorespiratory fitness.13 Consequently, there has been widespread interest in therapies to control heart rate, both in general medical and perioperative patients.1314More than 310 million surgical procedures are carried out worldwide each year, with mortality rates of up to 4%.1415 However, the results of the largest clinical trial demonstrated that β-block increased the risk of mortality.15 This has led to the suggestion that the optimal dose of β-blocker varies, and that preoperative heart rate might be used to determine the appropriate dosage in individual patients.16 However, this remains controversial, and the association between preoperative heart rate and postoperative cardiac complications has been explored in only a small number of studies.20 Except for the POISE Trial, none of these involved the routine measurement of cardiac biomarkers to identify myocardial injury, and statistical analyses used arbitrary predefined heart rate thresholds.1520 Thus, it remains unclear whether or not there is an increased relationship between preoperative heart rate and myocardial injury, or if there is a heart rate threshold at which the risk of postoperative myocardial injury increases.A number of trials have demonstrated that perioperative treatment with β-blockers, to lower heart rate, reduces the risk of perioperative myocardial infarction (MI).The aim of this analysis was to assess, in the perioperative setting, the relationships between heart rate and cardiovascular outcomes previously described in general medical patients. We hypothesized that elevated preoperative heart rate is associated with increased risk of myocardial injury, MI, and mortality within 30 days of surgery.45 Research ethics committees or boards approved the study at each site before patient recruitment commenced. The study was registered with ClinicalTrials.gov (NCT00512109).This was a predefined secondary analysis of data prospectively collected in the Vascular Events in Non-cardiac Surgery Patients Cohort Evaluation (VISION) study, an international prospective observational cohort study of clinical outcomes after non-cardiac surgery. The full methods have been published previously.45 Patients were excluded if they refused consent or if they had been previously enrolled in the study.Patients aged 45 yr or older undergoing non-cardiac surgery under regional or general anaesthesia with an expected overnight hospital stay were eligible for inclusion. Patients gave written informed consent before surgery or, where this was not possible (e.g. emergency surgery), consent was obtained within 24 h after surgery. Eight hospitals used a deferred consent process for patients who could not provide consent and for whom no next of kin was available.Supplementary file). Researchers collected data from patients and their medical notes. Preoperative heart rate was measured as part of routine care at each site and was defined as the last heart rate measurement recorded before induction of anaesthesia. Blood was sampled between 6 and 12 h after surgery and on days 1, 2, and 3 after surgery. Serum troponin T (TnT) concentration was measured using a Roche Diagnostics  fourth generation Elecsys™ assay. If TnT was ≥0.04 ng ml−1 , an ECG was performed. In the absence of dynamic ECG findings or clinical features of myocardial ischaemia, clinicians were encouraged to obtain an echocardiogram.A detailed data set was collected before and 30 days after surgery  were excluded. This definition and TnT threshold was previously defined using VISION data and is the definition of MINS recommended by the European Society of Anaesthesia and European Society of Intensive Care Medicine joint taskforce on clinical outcomes in perioperative medicine.421 Secondary outcome measures were MI and death within 30 days of surgery. Myocardial infarction was defined according to the third universal definition .21 Patients with a troponin elevation <0.04 ng ml−1 were not investigated for evidence of ischaemia.The primary outcome measure was myocardial injury after non-cardiac surgery (MINS), defined as TnT ≥0.03 ng ml2223 We corrected each multivariable model for covariates that were previously associated with MINS, cardiac events (including MI), or mortality in other perioperative epidemiological research, as follows: age , current atrial fibrillation, diabetes mellitus, hypertension, heart failure, coronary artery disease, peripheral vascular disease, previous stroke or transient ischaemic attack, estimated glomerular filtration rate , chronic obstructive pulmonary disease, neurosurgery, major surgery, and urgent or emergency surgery; these were considered as categorical variables in the multivariable models.452425 Full definitions are listed in the Supplementaryfile. Missing data were handled by list-wise deletion. The results of multivariable logistic regression analyses are presented as odds ratios (ORs) with 95% confidence intervals. Normally distributed data are expressed as the mean (sd), and non-normally distributed data are expressed as the median (interquartile range). Binary data are expressed as percentages.We used SPSS version 22  for the main statistical analysis. We ranked the sample according to integer values of preoperative heart rate and divided the sample into deciles, using cut-points closest to each 10th percentile, with approximately equal numbers of patients in each group. As a result of the distribution of patients, some groups contained more or fewer patients than average. The groups were compared for differences in baseline characteristics. We constructed multivariable logistic regression models for heart rate against each outcome measure, considering each decile as a categorical variable. We used deviation contrasts to compare each heart rate category with the unweighted average effect for the whole cohort because we did not want to isolate any particular heart rate decile as a reference category.−1) and the perioperative literature (>104 beats min−1).826 We dichotomized the sample according to each heart rate threshold and constructed multivariable logistic regression models for each outcome measure, corrected for the previous covariates. Heart rate above the threshold was considered as a categorical variable.Previous studies have investigated heart rate as a risk factor for cardiac complications using predefined heart rate thresholds. To allow comparisons between our findings and previous research, we repeated our analysis using two heart rate thresholds that were associated with MI or mortality in the general medical literature  to continuous variables within the model.2728 We used STATA version 14  to fit the most efficient polynomial model to our data and then repeated a logistic regression analysis using the polynomial functions of the independent variables.We repeated the multivariable logistic regression analyses using a single heart rate decile as the reference category, rather than the whole cohort. To determine the influence of preoperative atrial fibrillation, we excluded all patients with a history of atrial fibrillation and repeated the logistic regression analyses. Secondly, to determine the influence of emergency surgery, we excluded all emergency surgery patients and repeated the logistic regression analyses. It is plausible that an observed relationship between heart rate and one or more of the outcome measures could be confounded by the use of medications that influence heart rate. The most relevant agents in clinical practice are β-adrenoceptor antagonists (β-blockers) and the negatively chronotropic calcium channel blockers, diltiazem and verapamil. To determine the influence of these agents, we conducted a 4 We excluded patients with missing data describing preoperative heart rate or patient outcomes. Of 15 087 patients, 1197 (7.9%) sustained MINS, 454 of 16 007 patients (2.8%) sustained MI, and 315 of 16 037 patients (2.0%) died, within 30 days of surgery. Patients who were missing predefined covariates were excluded from multivariable analyses , diabetes mellitus (P<0.01), peripheral vascular disease (P<0.01), previous stroke or transient ischaemic attack (P<0.01), chronic obstructive pulmonary disease (P=0.02), estimated glomerular filtration rate <30 ml min−1 (P<0.01), and estimated glomerular filtration rate 30–44 ml min−1 (P<0.01).A total of 16 079 patients were recruited to the VISION study from 12 hospitals in eight countries between August 6, 2007 and January 11, 2011.−1) were associated with MINS , MI , and mortality . Heart rates in the ninth decile (88–96 beats min−1) were also associated with mortality , but not with MINS or MI. Heart rates in the eighth decile (83–87 beats min−1) and fifth decile (73–74 beats min−1) were associated with MINS , but not with MI or mortality. Heart rates in the lowest decile (<60 beats min−1) were associated with lower mortality rates than other deciles , but this group was not associated with MINS or MI , MI , and mortality , as shown in Table −1 were associated with MINS  and mortality , but not MI  as the reference category , except that heart rates in the lowest decile were no longer associated with postoperative mortality , heart rates 72–74 beats min−1 were no longer associated with myocardial injury , and heart rates 69–71 beats min−1 were associated with MI . To examine the potential confounding effect of preoperative tachyarrhythmia, we repeated the regression analyses excluding patients with current atrial fibrillation, the most common preoperative arrhythmia. When we excluded patients with current atrial fibrillation or emergency surgery, the results were very similar to the main results .Our principal findings remained similar when we repeated the regression analyses using a single decile . The ORs for MINS, MI, and 30 day mortality were 1.52 , 1.83 , and 2.90 , respectively. However, heart rates <60 beats min−1 were no longer negatively associated with mortality . The results of the multivariable fractional polynomial regression analysis confirm the linear association between heart rate and the probability of myocardial injury. The best-fitting model included one heart rate function that underwent a single linear transformation . A summary plot of this model is shown in Fig. The association between the highest decile of heart rate and each of the three outcome measures was not affected by exclusion of patients who received a β-blocker, a rate-limiting calcium channel blocker, or both within 24 h before surgery (−1) was consistently associated with higher incidences of each of these outcomes. Heart rates in the first decile (<60 beats min−1) were associated with a lower incidence of mortality, but not MINS or MI. We found similar, but weaker, associations with predefined heart rate thresholds of >70 and >104 beats min−1, which were identified from the existing general medical and perioperative literature. The absence of association between heart rates below the 10th decile and outcomes implies that the signal seen with the binary thresholds is attributable mainly to higher event rates in patients with heart rates >96 beats min−1. Multivariable fractional polynomial analysis suggests that the relationship between heart rate and myocardial injury is linear.The principal finding of this study is that elevated preoperative heart rate is associated with increased incidences of MINS, MI, and death within 30 days of surgery. When we examined the entire range of heart rates, the highest decile  patients received a β-blocker or negatively chronotropic calcium channel blocker within 24 h before surgery. After excluding these patients from the analysis, the independent association between heart rates >96 beats min−1 and the outcomes remained. However, the negative association between heart rates <60 beats min−1 and mortality was no longer statistically significant, suggesting that the observed association may be confounded by rate-controlling medication. Alternatively, they might suggest that rate-limiting medication was merely a marker of underlying heart disease.Our results contrast with those of population-based studies, in which incremental increases in resting heart rate are associated with higher long-term rates of cardiovascular events across the whole heart rate spectrum.829 The majority of perioperative MIs are thought to originate not from the rupture of atheromatous coronary plaque, as in the general population, but as the result of protracted myocardial ischaemia.7 The imbalance between myocardial oxygen supply and demand, and subsequent myocardial ischaemia, is promoted by multiple factors, including anaemia, hypertension, hypotension, and hypoxia.7 However, the most prominent candidate mechanism is tachycardia, induced by autonomic imbalance, postoperative pain, hypovolaemia, or reduction in heart rate-limiting medications, leading to increased oxygen consumption and resultant ischaemia.78 This is supported by evidence from animal studies, where tachycardia induces subendocardial myocardial necrosis.29 However, it is possible that tachycardia may simply be a marker of underlying conditions that contribute to myocardial injury, including systemic inflammation and sympathetic autonomic dysfunction.1332 Given this uncertainty, it is unclear whether therapeutic control of perioperative heart rate would influence clinical outcome.The observed associations between elevated preoperative heart rate and postoperative outcomes offer a plausible mechanism by which tachycardia could promote cardiac complications.35 Atrial fibrillation was present in only 6% of patients in the top decile, and the removal of these patients had little impact on our findings, nor did exclusion of patients taking β-blockers or rate-limiting calcium channel blockers, or patients undergoing emergency surgery.This study has several limitations. The influences of premedication and anxiety on heart rate are well established. In an attempt to standardize heart rate measurement, preoperative heart rate was recorded before and as close to induction of anaesthesia as possible. The potential confounding influence of atrial fibrillation, the commonest population-based tachyarrhythmia, was assessed both through the adjustment of the multivariable models and by a sensitivity analysis.38 Nor was the presence of a pacemaker recorded, although it is likely that these patients composed only a small percentage of the study population.The strengths of our analyses derive from the multicentre study design and large patient sample. The sample reflects a wide spectrum of non-cardiac surgery taking place in hospitals in a number of countries, making the results relevant to the majority of surgical patients. The routine measurement of TnT allowed us to identify subclinical myocardial injury in addition to subjective clinical outcomes. We planned the statistical analysis before taking custody of the data and used multivariable models to correct for confounding factors. However, like all observational studies, our results may be susceptible to unmeasured confounding. For example, the highest heart rate decile might include patients in whom the myocardial injury occurred before surgery, something we were unable to account for in our analysis.Elevated preoperative heart rate was associated with MINS, MI, and mortality within 30 days after surgery. This was primarily attributable to significantly higher event rates in patients in the highest decile of heart rate. Further research is needed to understand the effects of heart rate on postoperative myocardial injury and to clarify whether or not heart rate reduction in selected patients can safely reduce major perioperative myocardial ischaemic events.Design of the analysis plan: T.E.F.A., G.L.A., R.M.P., P.J.D., R.N.R., R.A.A.Data analysis: T.E.F.A., R.M.P., G.L.A.Drafting the manuscript: T.E.F.A., R.M.P., G.L.A.Revision of the manuscript after critical review: all authors.British Journal of Anaesthesia online.Supplementary material is available at British Journal of Anaesthesia. Roche Diagnostics provided the troponin T assays and some financial support for the VISION Study. P.J.D. has received other funding from Roche Diagnostics and Abbott Diagnostics for investigator-initiated studies. All other authors declare they have no conflicts of interest.The VISION Study funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation or approval of the article. R.M.P. has received equipment loans from LiDCO Ltd, a research grant from Circassia Holdings Ltd, and has performed consultancy work for Edwards Lifesciences, Covidien, and Massimo Inc. R.M.P. is a member of the editorial advisory board of the Canadian Institutes of Health Research (six grants); Heart and Stroke Foundation of Ontario (two grants); Academic Health Science Centres Alternative Funding Plan Innovation Fund Grant; Population Health Research Institute Grant; Clarity Research Group Grant; McMaster University, Department of Surgery, Surgical Associates Research Grant; Hamilton Health Science New Investigator Fund Grant; Hamilton Health Sciences Grant; Ontario Ministry of Resource and Innovation Grant; Stryker Canada, McMaster University, Department of Anesthesiology (two grants); Saint Joseph′s Healthcare, Department of Medicine (two grants); Father Sean O′Sullivan Research Centre (two grants); McMaster University, Department of Medicine (two grants); Hamilton Health Sciences Summer Studentships (six grants); McMaster University, Department of Clinical Epidemiology and Biostatistics Grant; McMaster University, Division of Cardiology Grant, and Canadian Network and Centre for Trials International Grant; Winnipeg Health Sciences Foundation Operating Grant; Diagnostic Services of Manitoba Research Grant; University of Manitoba, Faculty of Dentistry Operational Fund; Projeto Hospitais de Excelencia a Serviço do SUS grant from the Brazilian Ministry of Health in Partnership with Hcor ; School of Nursing, Universidad Industrial de Santander; Grupo de Cardiología Preventiva, Universidad Autónoma de Bucaramanga; Fundación Cardioinfantil Instituto de Cardiología; Alianza Diagnóstica SA; University of Malaya Research Grant; and University of Malaya, Penyelidikan Jangka Pendek Grant. Roche Diagnostics provided the troponin T assays and some financial support for the VISION Study. Medical Research Council and British Journal of Anaesthesia clinical research training fellowship (grant reference MR/M017974/1 to T.E.F.A.); National Institute for Health Research professorship (to R.P.); British Journal of Anaesthesia and Royal College of Anaesthetists basic science fellowship (to G.A.); National Research Foundation of South Africa (to R.N.R.); Heart and Stroke Foundation of Ontario Career Investigator Award (to P.J.D.); Yusuf Chair in Cardiology (P.J.D.).Funding for this study comes from more than 50 grants for VISION and its sub-studies:


There is a need for improved worldwide access to tissue iron quantification using T2* cardiovascular magnetic resonance (CMR). One route to facilitate this would be simple in-line T2* analysis widely available on MR scanners. We therefore compared our clinically validated and established T2* method at Royal Brompton Hospital (RBH T2*) against a novel work-in-progress (WIP) sequence with in-line T2* measurement from Siemens (WIP T2*).n = 22) and patients with iron overload (n = 78) were recruited . A 1.5 T study  was performed on all subjects. The same mid-ventricular short axis cardiac slice and transaxial slice through the liver were used to acquire both RBH T2* images and WIP T2* maps for each participant. Cardiac white blood (WB) and black blood (BB) sequences were acquired. Intraobserver, interobserver and interstudy reproducibility were measured on the same data from a subset of 20 participants.Healthy volunteers  and cardiac T2* values from 6.0 to 52.3 ms (median 31 ms). The coefficient of variance (CoV) values for direct comparison of T2* values by RBH and WIP were 6.1–7.8 % across techniques. Accurate delineation of the septum was difficult on some WIP T2* maps due to artefacts. The inability to manually correct for noise by truncation of erroneous later echo times led to some overestimation of T2* using WIP T2* compared with the RBH T2*. Reproducibility CoV results for RBH T2* ranged from 1.5 to 5.7 % which were better than the reproducibility of WIP T2* values of 4.1–16.6 %.Iron estimation using the T2* CMR sequence in combination with Siemens’ in-line data processing is generally satisfactory and may help facilitate global access to tissue iron assessment. The current automated T2* map technique is less good for tissue iron assessment with noisy data at low T2* values. Accurate and robust measurement of myocardial iron stores is essential for preventing cardiac disease and managing chelation treatment in patients with thalassemia, sickle cell disease, aplastic anemia, myelodysplasia, and other transfusion-dependant anemias –3. T2* cThe development of T2* CMR has made a great impact on patient management and survival, as no alternative method  gives reliable information about cardiac iron loading. In the UK where it was first introduced clinically, >70 % reductions in cardiac mortality for thalassemia major (TM) have been documented . HoweverAfter a decade of development, the single breath-hold multi-echo gradient CMR T2* sequence is available from the major vendors, including Siemens, Philips and GE. One recent approach to further increasing T2* access is the vendors’ attempt to develop an in-line processing algorithm to generate T2* maps immediately after the scan. This obviates the need for third-party software, with users being able to simply draw a region-of-interest (ROI) on the map generated in the scanner console. This may streamline clinical workflow with the additional advantage of decreased user interaction. One such product is provided by Siemens Healthcare , named the Works in Progress T2* package (WIP). However, there are little validation data on this type of potentially useful product. In this study therefore, we aimed to directly compare WIP T2* with the established T2* technique at Royal Brompton Hospital (RBH) on a population of healthy volunteers and patients with iron overload conditions.N = 100, 53 males, aged 13 to 81 years, median 34 years). Among patients referred for routine iron assessment, there were 39 with beta-thalassaemia major, 15 with sickle cell disease, 10 with hereditary hemochromatosis, and 14 with other iron overload conditions. The study was approved by the North-West Thames Ethics Committee. All participants gave written informed consent.A total of 22 healthy volunteers and 78 patients were recruited  equipped with high performance gradients and a six-element cardiac phased array coil and a spine array coil. The same mid-ventricular short axis cardiac slice and transaxial slice through the liver were used for both RBH T2* images (developed in-house based on the Siemens CV sequence) and WIP T2*  maps for each participant. Cardiac white blood (WB) and black blood (BB) and liver sequences , 15 wereFor the heart, a single 10 mm mid-ventricular short axis slice was imaged at eight echo-times . The BB sequences used double inversion recovery pulses to suppress the blood signal and data were acquired every other cardiac cycle, which made the effective sequence two cardiac cycles long. For the liver, a mid-liver transverse slice was acquired positioned to cover both lobes using the sequence optimised for liver iron load with the following acquisition parameters: flip angle of 20°, repetition time of 200 ms, 12 echo times , slice thickness of 10 mm. Fat saturation was applied and the liver images were acquired within a breath-hold of approximately 13 s.2) were drawn in homogenous areas of liver parenchyma, excluding blood vessels.For all cardiac analyses, a homogeneous full thickness ROI was drawn in the septum. Care was taken to exclude epicardial structures and blood pool from the contours. For all liver analyses, three large ROIs  at the later echo times. All T2* measurements were carried out on a personal computer using Thalassemia-Tools, a plug-in of CMRtools . For WIP T2* measurement, like-for-like ROIs were directly drawn on the magnitude images and copied to the T2* maps generated on the scanner and the mean ROI values were calculated for T2*. This was performed because of the difficulty of confidently identifying the myocardium on some T2* maps.n = 20) were ordered randomly. For the intra-observer reproducibility, all selected data were blindly reanalyzed by the same operator after 15 days. For the interobserver reproducibility, the data were analyzed by two independent operators blinded to each other’s T2* measurement. For interstudy reproducibility, repeated scans performed on the same day, were analyzed by the same observer blindly.In order to evaluate the intra and inter-observer reproducibility, all in-vivo data  of the differences as described by the Bland-Altman analysis. The coefficient of variation (CoV), defined as the SD of the differences between two independent measurements divided by their means and expressed as a percentage, was used to assess the intra- and inter-observer and inter-study variability. Summary data were expressed using the mean or median for normal and non-normal data respectively. Correlation analysis was performed using Pearson’s test. All participants underwent scans without complications and all scans were successfully analyzed. No data was excluded from analysis. Liver T2* values ranged from 0.8 ms to 35.7 ms median 5.1 ms) and cardiac T2* values from 6.0 ms to 52.3 ms (median 31 ms), both representing a wide spectrum of tissue iron loading conditions. Representative images acquired from a TM patient of the same mid-ventricular slice for RBH T2* and WIP T2* are shown in Fig.  ms and cR2 = 0.97, CoV = 6.1 %) between RBH and WIP techniques. For heart BB T2*, the correlation is shown in Fig. R2 = 0.95, CoV = 7.3 %). For liver T2*, the linear correlation between RBH and WIP T2* techniques is shown in Fig. R2 = 0.99, CoV = 7.8 %).For heart WB T2*, there was a linear correlation . There were also some differences between the WIP and RBH techniques in artefact scores, with RBH better for the white blood heart sequence (p < 0.001).The artefact scores are shown in Table There is a need for improved access to T2* CMR and more effort is needed to achieve this goal. Among these efforts, a dedicated T2* sequence combined with in-line processing has the promise to simplify T2* analysis and enable confident T2* measurement in less experienced centers. In this validation study, comparison of the RBH T2* values (being used as a gold-standard) and the WIP T2* values at 1.5 T showed good general agreement for heart and liver with clinically acceptable variances of 6.1 to 7.8 %. Our data suggest that the automated WIP technique may prove useful in clinical practice.Reproducibility of the RBH T2* and WIP techniques showed that the RBH T2* analyses had reproducibility that was in the region of 2-fold superior Table . The imaThere have been considerable efforts in parameter mapping development at the pixel level for tissue characterisation using CMR , 18. TheThere are limitations to this study. Cardiac T2* measurements were based on imaging and analysing the septum, as myocardial T2* can only be measured reliably in this region due to susceptibility artefacts. However, mid-ventricular septal T2* is highly representative of global iron concentration , and theThere have been significant technical advances in T2* CMR over recent years and it is now the method of choice for cardiac and hepatic iron quantification in clinical practice. T2* sequence in combination with vendor’s inline data processing development has the promise to improve global access to tissue iron assessment. However, due to their inherent vulnerability to low SNR, current T2* mapping and inline analysis techniques are not yet fully optimised for tissue iron assessment. Further scientific development is needed to improve the mapping technique, which should be followed by validation in a large patient cohort.