Many patients with Tetralogy of Fallot (TOF) have residual pulmonic stenosis and/or regurgitation after surgical repair, leading to maladaptive right ventricular (RV) remodeling. Cardiovascular magnetic resonance (CMR) is currently the gold standard for evaluating RV size and function. Analysis of regional volume and three-dimensional (3D) curvature of the RV from CMR images may provide new insights into the remodeling process. The aim of this study is to describe RV remodeling by characterizing regional endocardial surface curvature and function in patients with TOF.CMR (1.5T Philips Achieva) was performed in subjects with repaired TOF  and healthy volunteers . The RV end-diastolic and end-systolic endocardial surfaces were manually segmented from a contiguous stack of short axis cine slices to construct a 3D model using custom software (figure). This model was used to measure regional volume and ejection fraction for the RV inflow, outflow, and trabecular regions. Local endocardial surface curvature was displayed on a color map of the 3D volume surface and regional curvature was calculated for the RV inflow, outflow, trabecular, free wall, and septal segments. The values for curvature were indexed to volume to remove the influence of volume between regions. The parameters from individuals with TOF were compared to those acquired from the healthy volunteers.As shown in the table, individuals with TOF had larger global RV volume and reduced ejection fraction when compared to controls. The trabecular region had relatively preserved ejection fraction, despite exhibiting the most enlargement. Conversely, the outflow and inflow regions had greater reductions in ejection fraction but only mild enlargement. The Trabecular region enlargement coincided with increased regional curvature, which was not as striking in the inflow and outflow regions. Those with TOF had higher overall free wall curvature. Septal curvature in TOF patients was higher (slightly convex) compared to controls (slightly concave). Global curvature, combining all septal and free wall regions, was higher in TOF patients.Using analysis of RV 3D regional curvature and volumes from CMR images, we show that individuals with repaired TOF have regional variation in RV remodeling and function. Further evaluation is required to understand the clinical implications of this variable remodeling.


In this study we aimed to translate and validate T1ρ-mapping for endogenous detection of chronic MI in patients.Detection of cardiac fibrosis based on endogenous MR characteristics of the myocardium would yield a measurement that can provide quantitative information, is independent of contrast agent concentration, renal function and timing . In 21 patients  underwent an MRI exam 2 to 12 months after clinically confirmed myocardial infarction. The study was performed on a Philips Achieva 1.5 T MR scanner , using a 5-channel cardiac receive coil. Written informed consent was obtained from all patients.In vivo MR: T1ρ-mapping was performed using a T1ρ-prepared balanced SSFP sequence. 4 images with different spin-lock preparation times (SL) with an amplitude of 750 Hz were acquired . Bandwidth/pixel = 530 Hz, TE/TR = 1.94/3.9 ms, resolution = 1.5x1.65 mm, slice thickness = 6 mm, FOV = 288x288 mm2, flip angle = 50 degrees, 2 TFE shots, NSA = 2, SENSE = 1.5. Images were acquired in late diastole during expiration breath holds, with an R-R interval of 3 beats. LGE MRI was performed 15 minutes after contrast injection (0.2 ml/kg contrast agent (Gadovist). .1ρ-maps were calculated by pixelwise fitting of a mono-exponential decay function in Matlab (Mathworks). The LGE images and T1ρ maps were scored using the 17 segments AHA-model.T1ρ relaxation time was significantly higher in the infarct region (79 ± 11 ms), compared to healthy remote myocardium (54 ± 6 ms), p<0.0005. The myocardial region with an elevated T1ρ relaxation time closely correlated with the corresponding LGE results (figure 1ρ-maps was 74 % (table T1ρ-mapping for detection of infarct area in patients with a chronic myocardial infarction. Since this method is quantitative, requires no contrast agent, and thus is independent on renal function and timing, it may provide additional information or be an alternative to the LGE method in patients with severe renal failure.We have shown the feasibility of native TN/A.


Alström syndrome is a rare inherited ciliopathy with progressive multisystem involvement. Dilated cardiomyopathy is common in infancy and recurs or presents de novo in adults with high rates of premature cardiovascular death. Although Alström syndrome is characterised by fibrosis in solid organs such as the liver, the pathogenesis of related cardiomyopathy are not clear. To date it is not known whether diffuse interstitial myocardial fibrosis is present before the onset of heart failure symptoms or changes in conventional parameters of left ventricular function.In this observational study, 26 patients with Alström syndrome  without symptomatic cardiovascular disease were recruited from a single centre and compared to matched healthy controls. All subjects underwent cardiac MRI (1.5 T) to assess ventricular function, diffuse interstitial myocardial fibrosis by measurement of extracellular volume on T1-mapping (MOLLI) and coarse replacement fibrosis using standard late gadolinium enhancement imaging.Global extracellular volume was increased in Alström syndrome with wider variation compared to controls . Left ventricular long axis function and global longitudinal strain were impaired in Alström syndrome without change in ejection fraction, ventricular size or atrial stress (NT-proBNP) (p < 0.05). Global extracellular volume was associated with reduced peak systolic longitudinal strain  and strain rate , increased QTc interval  and serum triglycerides . Nine (35 %) patients had diffuse mid-wall late gadolinium enhancement in a non-coronary artery distribution.Diffuse interstitial myocardial fibrosis is common in Alström syndrome and is associated with impaired left ventricular systolic function. Serial studies are required to determine whether global extracellular volume may be an independent imaging biomarker of vulnerability to dilated cardiomyopathy and heart failure. Estim00 charact-mortem . This hat-mortem , 11. Altt-mortem . Diffuset-mortem . This liThe profound metabolic disturbances which characterise ALMS include severe insulin resistance, activation of the renin angiotensin aldosterone system and raised serum triglycerides - each of which has a potential role in the development of myocardial fibrosis , 13–15. A propsoective cohort observational study performed between March 2012 and November 2013.In total, 26 consecutive adults with genetically proven ALMS attending the National Centre for Rare Disease at the Queen Elizabeth Hospital Birmingham, England were studied prospectively as part of standard clinical care. Two other patients were seen at the National Centre during this time period but did not proceed with CMR due to contra-indications . Patients were compared to gender and age matched healthy controls with no history of cardiac disease recruited as part of an on-going clinical study .This study was approved by the National Research Ethics Service and all patients provided written informed consent to participate (12/WM/0250).Consent was obtained for contrast enhanced CMR . Left ventricular (LV) dimensions, volumes and mass were acquired in line with standard CMR protocols . Mitral Analysis was performed off-line using Argus Software (Siemens®) according to the Society for Cardiovascular MR guidelines for reporting CMR with parameters indexed to height and body surface area where appropriate . Tagged Quantitative parametric images of myocardial ECV were generated with manual contouring to define a region of interest (ROI) within the LV myocardium in the ventricular septum (4-chamber view) and at basal and mid ventricular level (short-axis) on matched pre and post contrast images . Care was taken to avoid contaminating T1 measurements at the myocardial-blood pool interface. T1 time in each ROI was recorded and used to calculate myocardial extracellular volume (ECV) by validated formulae .\documenHCT refers to the haematocrit recorded on a venous blood sample at the time of scan, ΔR1 = 1/T1 post contrast – 1/T1 pre contrast. The ECV was assessed in the left ventricle from the basal and mid ventricular levels, averaged to yield a “global ECV” measurement. Further details on the methods used have been published , 22.Venous blood samples were collected for routine haematology, biochemistry and lipid profiles. Serum N-terminal pro B Natriuretic peptide  was measured by sandwich immunoassay with magnetic particle separation and chemiluminescent detection on an E170 analyser  with a lower limit of detection of 0.6 pmol/L. Plasma renin was measured using an immunoradiometric assay  with age and position reference intervals and a detection limit of 5 ng/L. Aldosterone was measured by competitive radioimmunoassay  which has reference intervals dependent on position with a detection limit of 60 pmol/L. C-peptide (pmol/L)/insulin (pmol/L) were also measured .Subjects underwent 24 h ambulatory blood pressure monitoring using a British Society of Hypertension approved protocol .Standard 12-lead electrocardiograms were recorded in each subject within 24 h of the CMR scan, with measurement of PR interval, QRS duration and QTc intervals using standard methodology (Bazett’s formula for QTc).Continuous variables are expressed as mean ± standard deviation (SD) if normally distributed or median (interquartile range) if non-normally distributed by the Shapiro-Wilk test. Paired group comparisons were performed using independent T-test, Mann–Whitney and one-way analysis if variance with Bonferroni post hoc tests, as appropriate. Correlations between variables were assessed by Pearson if normally distributed and Spearman analyses if non-normally distributed. A multivariable regression model was used to assess predictors of ECV using variables associated with myocardial fibrosis. Statistical tests were two tailed and a p-value <0.05 was considered to indicate statistical significance.In total, 26 ALMS patients were compared with healthy controls . Subject genetic and demographic profiles are presented in Table Patients with ALMS demonstrated marked metabolic derangements Table . All wer2.7. There was no difference in LV ejection fraction (EF) but longitudinal function (MAPSE) was reduced . Absolute LV mass did not differ between groups but was increased when indexed to heighted Table .Table 3CLeft ventricular global longitudinal peak systolic strain and strain rate were reduced in ALMS Table .−1 ± 0.11 vs. 0.83 s−1 ± 0.15, p < 0.01) and reduced early diastolic strain rate . Fourteen patients (54 %) had an ECV above the upper limit (0.279) for controls. Five patients had ECV above the upper limit for matched normal controls in the absence of LGE  patients with ALMS (two with a history of infantile cardiomyopathy). An example is shown in Fig. 5 % patieAll ALMS patients were in sinus rhythm with normal atrial activation , ventricular depolarisation (QRS duration 88 ms ± 16) and ventricular repolarisation . Patients with ECV above the upper limit of the range for matched controls had increased QTc .2.7. Serum triglycerides  and QTc  also correlated with ECV .ECV correlated with age , global longitudinal peak systolic strain , peak systolic strain rate , MAPSE , but not ejection fraction, NT-BNP or LV mass/heightTwo patients Table  and evidInterstitial myocardial fibrosis assessed using CMR T1 mapping, was evident in over 50 % of patients with ALMS. Coarse fibrosis within the LV myocardium was detected in keeping with previous reports but a further 20 % of patients were shown to have interstitial fibrosis missed using conventional LGE alone. Expansion of the ECV was associated with impaired global LV systolic deformation, impaired LV diastolic function and increased QT interval.. Impairment of global longitudinal strain and strain rate preceded any change in ejection fraction and without abnormality of conventional markers of elevated LV end-diastolic pressure and atrial stretch, including both NT pro-BNP and left atrial volume. This finding raises the possibility that surveillance of ALMS for evidence of cardiomyopathy using NT pro-BNP may be inadequate. In contrast to previous echocardiographic studies  that havAlthough ALMS is a rare autosomal recessive genetic disorder, there is much interest in understanding the disease as a monogenic model for end-organ fibrosis which has been proven to affect the liver and kidneys . The incWe acknowledge that while mean global ECV was higher than controls in this study, expansion of the ECV was not universal and there was considerable dispersion of ECV values within the range of normal healthy controls. Indeed, 40 % of patients had a native pre-contrast myocardial T1 values below the cut off for healthy volunteers (943 ms) raising the possibility of myocardial fat deposition or pseudonormalization of T1 due to the combined presence of lipid and fibrosis within the LV. This significant inter-individual variation suggests that development of fibrosis is not an inevitable consequence of the genetic defect alone and that environmental factors may also play an important role. Further serial studies are warranted in ALMS to determine whether those with higher ECV are susceptible to adverse cardiovascular outcomes, as has been shown to be the case in other populations .Despite the fact that ALMS patients are characterised by obesity, severe insulin resistance and metabolic syndrome , 2, reduAn unusual feature of ALMS is the occurrence of infantile cardiomyopathy within the first few months of life which, if not fatal during the acute stage, may be followed by an apparent complete recovery . Adults ALMS1 mutation on fibroblast expression or to the severe metabolic disturbance warrants further study [Given the small sample size and narrow age range of patients with this rare disease, we were underpowered to show some relationships reported previously in ECV . This iser study , 34. Dueer study .Diffuse interstitial fibrosis is common in asymptomatic patients with ALMS and is associated with abnormalities of LV systolic and diastolic function. The presence of cardiac fibrosis may be actively modulated by the severity of metabolic dysfunction, with elevated triglycerides a potential marker or intermediary. Expansion of the ECV is an imaging biomarker of cardiovascular vulnerability that demands longitudinal study in ALMS.


Pixel-wise T2* maps based on breath-held segmented image acquisition are prone to ghost artifacts in instances of poor breath-holding or cardiac arrhythmia. Single shot imaging is inherently immune to ghost type artifacts. We propose a free-breathing method based on respiratory motion corrected single shot imaging with averaging to improve the signal to noise ratio.Images were acquired using a multi-echo gradient recalled echo sequence and T2* maps were calculated at each pixel by exponential fitting. For 40 subjects (2 cohorts), two acquisition protocols were compared: (1) a breath-held, segmented acquisition, and (2) a free-breathing, single-shot multiple repetition respiratory motion corrected average. T2* measurements in the interventricular septum and liver were compared for the 2-methods in all studies with diagnostic image quality.FB = 0.95 x T2*BH + 0.41, r2 = 0.93, N = 39 measurements, and in cohort #2, T2*FB = 0.98 x T2*BH + 0.05, r2 > 0.99, N = 22 measurements).In cohort 1 (N = 28) with age 51.4 ± 17.6 (m ± SD) including 1 subject with severe myocardial iron overload, there were 8 non-diagnostic breath-held studies due to poor image quality resulting from ghost artifacts caused by respiratory motion or arrhythmias. In cohort 2 (N = 12) with age 30.9 ± 7.5 (m ± SD), including 7 subjects with severe myocardial iron overload and 4 subjects with mild iron overload, a single subject was unable to breath-hold. Free-breathing motion corrected T2* maps were of diagnostic quality in all 40 subjects. T2* measurements were in excellent agreement (In cohort #1, T2*A free-breathing approach to T2* mapping is demonstrated to produce consistently good quality maps in the presence of respiratory motion and arrhythmias. Breath-held, segmented T2*-measurement is the gold standard method using cardiovascular magnetic resonance (CMR) for diagnosis of diseases involving accumulation of iron in the liver and heart -3. QuantPixel-wise T2* maps based on breath-held segmented image acquisition tend to be fairly noisy and prone to artifacts due to the relatively long breath-hold durations. We propose a free-breathing method based on respiratory motion corrected single shot imaging with averaging to improve the signal to noise. Single shot imaging is inherently immune to ghost type artifacts. The proposed fitting uses a new automatic truncation method to mitigate noise bias related errors by discarding long echo time measurements based on measured SNR.Images were acquired using an investigational prototype  multi-eci = A exp(−TEi/T2*) where A is the signal amplitude, and TEi is the echo time of the i-th image. Fitting used the downhill simplex minimization algorithm proposed by Nelder and Mead [The T2* was estimated pixel-wise by fitting to a 2-parameter model Sand Mead . Free-brand Mead  was usedand Mead . This reand Mead  found thPixel-wise fitting was integrated with the scanner for in-line operation using the Gadgetron framework . For theThe study was divided into 2 parts. The initial cohort of patients was imaged at NIH to demonstrate initial feasibility. In cohort 1, patients (N = 28) included in the study included N = 9 subjects referred specifically for evaluation of iron overload in both the liver and heart; the remainder of this cohort were referred for other known or suspected cardiac disease. Subject were age 51.5 ± 17.6 (mean ± SD) ranging from 20 to 81 .Following initial feasibility, a second cohort of patients (N = 12) with known Thalassemia was imaged in London in order to acquire additional data with myocardial iron overload. In cohort 2, subjects were age 30.9 ± 7.5 (m ± SD) ranging from 18 to 42 . In-vivo data was acquired using 2 imaging protocols to compare the breath-held and free breathing approaches. For subjects with low myocardial T2*, a lower spatial resolution protocol was additionally acquired in order to acquire data at shorter echo times (TE). A single mid-ventricular short axis slice was acquired for each subject. An additional 4-chamber view was acquired in several subjects. This study was approved by the local Institutional Review Boards of the National Heart, Lung, and Blood Institute, Royal Brompton Hospital, and the Heart Hospital, London, UK, and all subjects gave written informed consent to participate.Imaging was performed on 1.5 T MAGNETOM Aera and MAGNETOM Avanto systems , equipped with a 45 mT/m and 200 T/m/s gradient systems and a surface coil array with 32 channels (Avanto) or 30 channels (AERA). For studies performed with the Aera, a local box shim was performed over the heart region to minimize dephasing due to local gradients. Heart rates were measured from the recorded ECG.Analysis of image quality was conducted by 2 observers using the following 5 point scale: 1 - Very poor image quality with unusable images; 2 - Average image quality, not all of septum clearly seen and a lot of artifact; 3 - Good image quality with moderate septal artifact; 4 - Very good quality, with minimal septal artifacts; 5 - Excellent image quality with no significant septal artifact. The scoring criteria were adopted from Smith, et al.  where thT2*-maps were acquired with both protocols in all 28 subjects. A single subject with hemochromatosis had severe myocardial iron overload with T2* < 5 ms. T2* for the remaining subjects were considered normal in the heart (>20 ms) . The meaFB = 0.95 × T2*BH + 0.41, r2 = 0.93, N = 39). The liver was not imaged in the short axis slice for 1 subject. Differences between ROI measurements for the LV septum and liver ROIs combined (N = 39) are displayed in a Bland Altman plot , T2*FB160 = 0.98 × T2*BH256 + 0.05 , and T2*FB128 = 0.96 × T2*BH256 + 0.38  for the 3 comparisons.T2* maps were acquired in 12 subjects of which 11 were of diagnostic quality for both FB and BH method. A single subject was unable to breath-hold. The mean heart rate was 64.2 ± 12.7 bpm (mean ± SD), ranging from 50 to 90 bpm. In this 2nd cohort, myocardial T2* indicated severe myocardial iron overload (<10 ms) in 7 subjects, mild iron overload in 4 subjects (14 ms < T2* < 20 ms), and normal (>20 ms) in 1 subject. T2* maps were acquired using 4 protocols, and the myocardial T2* in a septal ROI was compared for the BH128, FB160, and FB128 protocols against the BH256 protocol. Comparisons including scatter plots and Bland-Altman plots are shown in Figure Quality scores were higher for FB than for BH . In cohort 1, scores for reader #1 were 2.6 ± 1.3 and 3.6 ± 1.1  for the breath-held segmented and free-breathing MOCO protocols, respectively. Quality scores for reader #2 were 2.5 ± 1.2 and 3.4 ± 0.7  for the breath-held segmented and free-breathing MOCO protocols, respectively. Reader #1 found the MOCO method to have an average score that was 1.0 higher than the breath-held method, and reader #2 found the MOCO method to be 0.9 better than breath-held. In cohort 1, reader #1 scored the breath-hold, segmented maps for 6 studies as non-diagnostic, and reader #2 scored 8 studies as non-diagnostic including the same 6 as reader #1. All free breathing studies were judged as diagnostic quality. One of the patients referred for evaluation of iron overload had non-diagnostic quality breath-held T2* maps and was positive for iron overload from the free breathing protocol (T2* = 5.4 ms).In cohort 2, quality scores for reader #1 were 4.3 ± 1.1 and 4.8 ± 0.5  for the breath-held segmented and free-breathing MOCO protocols, respectively. Quality scores for reader #2 were 3.8 ± 1.2 and 3.9 ± 0.9  for the breath-held segmented and free-breathing MOCO protocols, respectively. Reader #1 found the MOCO method to have an average score that was 0.5 higher than the breath-held method, and reader #2 found the MOCO method to be 0.2 better than breath-held. In cohort 2, there was a single study for which the BH maps were deemed to be non-diagnostic by both readers.Example T2* maps for both methods are shown Figure  for 4 suHeterogeneity of R2* = 1/T2* (iron deposition) was noted in several of the subjects with severe iron overload with a transmural gradient having increased R2* epicardially Figure  consisteThe proposed free-breathing MOCO approach to T2* mapping produces consistently good quality maps in the presence of respiratory motion and arrhythmias. MOCO T2* maps have fewer artifacts than current breath-hold segmented protocols and measurements of T2* are in excellent agreement with the breath-hold segmented protocols in subjects who are capable of breath-holding. In this study, the cohort 1 population was older, less capable of breath-holding, and had a number of instances of significant arrhythmias, compared to the cohort 2 which was a smaller group of younger age. Patients in cohort 2 that were invited to take part in this research study were generally more cooperative and capable of breath-holding than expected in routine clinical practice.The protocol chosen for breath-held segmented T2* imaging in the heart was the protocol in use by our institution and similar to reported protocols ,9. A numThe MOCO scans used 8 averages (of 16 repetitions) which improved the SNR thereby mitigating the parallel imaging loss. The complex averaging approach prevents a build-up of noise bias with increasing averaging, so the number of images acquired and averaged using the free-breathing MOCO approach can be increased to further improve the quality of maps. The poor temporal resolution of 345 ms (scan window) of the single shot method does not result in ghosting but rather a blurring or loss of spatial resolution. Despite the temporal resolution, the MOCO method was highly robust  and provided high image quality maps.A free-breathing approach to T2* mapping is demonstrated to produce consistently good quality maps in the presence of respiratory motion and arrhythmias and with a similar total scan time as existing breath-hold T2* measurement techniques. The approach is fully automatic including the truncation of long echo time measurements at low SNR to mitigate noise bias.


The principal determinants of chronic left ventricular(LV) dysfunction are reduced myocardial contractility and afterload excess due to adverse LV remodeling. To determine the relative contribution of each to a given instance of LV dysfunction, reliable quantitative indices of both myocardial contractility and afterload are needed. At the LV chamber level, ventricular volume and LV pressure can be used in a ventricular elastance model. But at the myocardial level, afterload must be normalized per unit of myocardium, conventionally done using wall stress (WS) calculations, while myocardial function is best characterized as systolic myocardial deformation, or strain (ST). Prior experimental model studies have suggested that the ratio of strain to afterload may be an effective contractility index. However, this has not been evaluated in human disease. We have recently shown that a nongeometric LV end-systolic afterload index  × volume(V))/LV mass(M), or PV/M), may be superior to conventional circumferential WS (CWS) as a quantitative measure of afterload at the myocardial level, and correlates more closely than CWS with circumferential ST(CST), Therefore, we evaluated the ratios CST/CWS and CST/PV/M, as candidate contractility indices in normals(NL) and in patients with nonischemic dilated cardiomyopathy(CM).In NLs  and CM we obtained breathhold volumetric CMR cines, SPAMM tagged cines and cuff systolic blood pressure and derived EF, global circumferential strain(CST) and mean strain rate(CSR), using feature-tracking(FT) ST, (TomTec Imaging Systems) and in a subset, HARP ST(Diagnosoft). End-systolic stress) and PV/M were also determined.Table  EF, CST : Strain/stress and strain/PV/M ratios are promising noninvasive myocardial contractile indices which can depict the contribution of contractile depression to reduced myocardial function. However, demonstration of the sensitivity of these indices to changes in inotropic state are also needed to validate these measures for potential research and clinical applications.St. Francis Research Foundation.


This may lead to more time-efficient data collection by reducing the field of view (FoV) or may improve image quality by suppressing artefacts from outside the area of interest. Meanwhile, T2-Preparation, or T2-Prep, is a magnetization preparation scheme used to improve blood/myocardium contrast. We propose incorporating a "pencil-beam" 2D RF pulse into a T2-Prep module, so as to produce a "2D T2-Prep" that combines T2-weighting with an intrinsic spatial selectivity.The first RF pulse of a +90°,180°,180°,-90° adiabatic T2-Prep was replaced with a jinc-shaped RF pulse and spiral gradients (Figure The simulated excitation profile of the 2D pulse can be seen in Figure A 2D T2-Prep shows promise to both reduce respiratory motion artefacts and decrease scan time, while preserving the T2-weighting of a conventional T2-Prep. It should thus be considered as a potential tool in accelerated cardiac imaging.


Objective: The purpose of this study was to assess central (aortic) vascular dysfunction in post renal transplant patients by high-resolution cardiovascular magnetic resonance imaging (CMR). Background: Renal transplant recipients are at increased risk of cardiovascular (CV) disease. The cardiac phenotype in post-transplant recipients is not well defined. A recent study suggested myocardial perfusion is impaired in renal transplant patients irrespective of the degree of left ventricular hypertrophy.We hypotMethods: Twenty-five asymptomatic renal transplant patients (RT) and 17 hypertensive controls (HT) underwent CMR scanning at 1.5 T. Myocardial function, late enhancement, aortic pulse wave velocity and first-pass perfusion at rest and stress was performed. Myocardial Perfusion Reserve Index (MPRI) was calculated as the ratio of hyperemic to resting myocardial blood flow by dividing the myocardial perfusion at stress by rest perfusion (corrected to rate pressure product). Pulse wave velocity (PWV) was calculated as the ratio between the distance and time from ascending aorta to descending aorta at the level of main pulmonary artery. Statistical analyses were performed using mixed effects modelling for MPRI and linear regression for relationship between MPRI and PWV.Results: Baseline clinical characteristics were similar for RT and HT control groups. Mean inter-ventricular septal thickness and LV mass indexed to body surface area were similar in both RT cases and HT controls. MPRI was significantly lower in the RT group compared to the HT group , globally and in all three coronary artery territories[Conclusions: In our cohort population, there is no evidence of increased aortic stiffness in post renal transplant patients compared to hypertensive patients. Although these patients demonstrate impaired myocardial perfusion reserve, this is not correlated with increased aortic stiffness.None.


Despite being the gold standard for left ventricular function evaluation, traditional SSFP sequences still require multiple breath-holds and a relatively long scan time. This extends total duration of the exam, especially in children or adults with impaired cardiopulmonary capacity. We sought to compare a technique employing a prototype sparse sampling with iterative reconstruction (SSIR) for rapid evaluation of the left ventricle  in a single breath-hold and free-breathing (FB) compared to traditional SSFP sequences and temporal parallel imaging methods.Patients undergoing routine clinical CMR for iron deposition evaluation with normal myocardial iron were evaluated with five different short axis cine techniques: traditional SSFP with 4-5 breath-holds, temporal parallel acquisition technique with 6-factor acceleration (TPAT6) in two breath-holds, SSIR with acceleration factor of 11.5x in one breath-hold, TPAT6 FB and SSIR FB. Left ventricular global function, diastolic and systolic volumes and mass were compared using repeated measures ANOVA and Bland-Altman plots. Traditional SNR and CNR were not used due to inherent properties of SSIR methods but a comparison of the ratio between left ventricular cavity blood and myocardium signal was performed to assess contrast among borders used for ROI tracings.Fifty consecutive patients  completed all five sequences. An example of images at diastole and systole is demonstrated in Figure The use of a rapid prototype SSIR cine sequence in FB provides feasible and accurate evaluation of left ventricular function and volumes, with small deviations in diastolic volume and mass compared to traditional SSFP sequences. The same results were also observed in the pediatric group, demonstrating the possible usefulness of the sequence for fast evaluation of both adults and children in routine practice.N/A.


APLNR) in a population consisting of 1,751 CAD cases and 1,022 controls. Variant rs9943582 was not associated with CAD, but among CAD patients, it showed significant association with left ventricular systolic dysfunction (431 CAD patients with left ventricular systolic dysfunction (LV ejection fraction or LVEF< 40%) versus 1,046 CAD patients without LV systolic dysfunction (LVEF>50%) . Moreover, rs9943582 also showed significant association with quantitative echocardiographic parameters, including left ventricular end-diastolic diameter , left atrial size  and LVEF . Our findings demonstrate that allele A of rs9943582 was significantly associated with left ventricular systolic dysfunction, left ventricular end-diastolic diameter, the left atrial diameter and LVEF in the CAD population, which suggests an important role of the apelin/APJ system in the pathology of heart failure associated with ischemic heart disease.Heart failure affects 1–2% of the adult population worldwide and coronary artery disease (CAD) is the underlying etiology of heart failure in 70% of the patients. The pathway of apelin and its apelin receptor (APJ) was implicated in the pathogenesis of heart failure in animal models, but a similar role in humans is unknown. We studied a functional variant, rs9943582 (-154G/A), at the 5’-untranslated region, that was associated with decreased expression of the APJ receptor gene ( Heart failure (HF) is an inexorable disease associated with an unacceptably high rate of morbidity and mortality. In developed countries, about 2% of adults suffer from heart failure, and this rate increases to 6–10% in people over the age of 65 years [Left ventricular systolic dysfunction (LVSD) is a complex clinical syndrome that can result from structural or functional cardiac disorders that impair the ability of the ventricle to eject blood . It is tThe most common cause of HF is CAD ,6. A 13 In addition to the classic risk factors such as smoking, hypertension, hypercholesterolemia, diabetes mellitus and obesity, genetic factors also contribute significantly to the development of HF ,8,9. Genangiotensin receptor-like1 gene, AGTRL1 or APLNR) is a G-protein-coupled receptor (GPCR), which was identified as the receptor for the adipokine apelin [i, and exerted a positive effect on cardiac contractility, and may play an important role in the pathology of HF [APLNR knockout mice showed that APJ receptor could induce a pathological stretch signaling pathway and triggered myocardial hypertrophy under the condition of pressure overloading. The activation of APJ by apelin can blunt the stretch-mediated myocardial hypertrophy. These results showed that the APJ might exert a complex effect on the pathology of HF [The apelin receptor (APJ) .The study cohort contained 1,751 CAD patients evaluated by coronary angiography. We followed the ACC/AHA criteria, and classified individuals with ≥70% luminal stenosis in at least one main vessel, percutaneous coronary angioplasty, coronary artery bypass graft or MI as CAD cases. MI was defined as typical chest pain of >30 min, characteristic electrocardiographic features of acute MI, and elevation of cardiac enzymes. Subjects with childhood hypertension, congenital heart disease, and type I diabetes mellitus were excluded. Gensini scores were calculated to evaluate the severity of coronary atherosclerosis . We alsoFor analysis of the association of rs9943582 with HF in CAD patients, we divided the CAD patients into two sub-groups according to the left ventricle performance by echocardiography, and performed a case-control association analysis. The left ventricle systolic dysfunction (LVSD) sub-group was defined as CAD patients who had a left ventricle ejection fraction (LVEF) of less than 40%, and the normal LVEF sub-group was defined as CAD patients with a LVEF of greater than 50% ,19. LVSDEchocardiographic measurements of left ventricular internal dimension, thicknesses of the interventricular septum, LV thickness of the posterior wall, the diameter of the aortic root  and the left atrium size at end-systolic were obtained by using a leading edge technique and on average measurements in 3 cardiac cycles according to the American Society of Echocardiography guidelines . DemograGenomic DNA was extracted from venous blood samples using the Wizard Genomic DNA Purification Kit (Promega Corporation) following the protocol of the manufacturer.Genotyping for SNP rs9943582 was performed using a SYTO9 fluorescent dye (Invitrogen Inc) based High Resolution Melt (HRM) method on a Rotor-gene 6200 System (Qiagen Inc) according to the protocol of the manufacturer. In brief, a short fragment containing SNP rs9943582 was amplified with the forward primer of 5’-ACCACTTCCTGCCTGCCCTTTA-3’ and a reverse primer of 5’-ACACCCTCCTTGCTCCCTACCA-3’ in a final concentration of 5μM SYTO9 fluorescent dye. Then the PCR products were genotyped by HRM analysis. DNA samples with known genotypes were used as positive controls, and appropriate negative controls were also included in every genotyping batch to ensure the quality. The quality of genotyping was also ensured by direct DNA sequencing analysis of 50 randomly selected samples (100% consistent rate between the two methods).P values were calculated using 100,000 Monte Carlo simulations. Echocardiographic parameters including LV diastolic internal dimension, LA size, thicknesses of the interventricular septum, LV thickness of the posterior wall, diameter of the aortic root and LVEF were considered as continuous traits and linear regression was used to analyze the association between SNP and these traits. The association was quantified by the regression slope (β), its standard error (SE), and P value. The analysis was performed using SPSS version 17.0.Statistical analysis was performed as previously reported ,22. Chi-Hardy-Weinberg linkage disequilibrium test was carried out using PLINK. Statistical Power analysis was performed by a free software- PS: Power and Sample Size Calculation .Tables 3. The population for association analysis between rs9943582 and CAD consisted of 1,751 CAD patients and 1,022 controls and their characteristics are shown in Table 1. Among the CAD patients, 431 patients showed LVSD (LVEF<40%), whereas 1,046 patients had normal LVEF (>50%) (Table 2). The basic characteristics of these two sub-populations are shown in Table 2. We used Gensini scores to evaluate the severity of coronary atherosclerosis of the CAD patients and found no significant differences between the CAD group with LVSD and the CAD group with normal LVEF . The detailed echocardiographic parameters for the two sub-populations are shown in Table 3, and include LV diastolic internal dimension, thicknesses of the interventricular septum, LV thickness of the posterior wall, diameter of the aortic root, left atrium size and LVEF.Clinical characteristics of all study populations are shown in Statistical power analyses indicated that our study populations provided a sufficient power to detect an association of rs9943582 with CAD (98% power) or LVSD (82% power) assuming an odds ratio (OR) of 1.3 and an alpha level of 0.05.P = 0.42). We did not detect any significant association between SNP rs9943582 and the risk of CAD in the GeneID population  (Table 4). The association remained non-significant (P-adj = 0.22) after adjusting for covariates of gender, age, smoking, hypertension, diabetes and lipids concentrations  by multivariate logistic regression (Table 4).Distributions of rs9943582 genotypes did not deviate from the Hardy–Weinberg equilibrium in 1,022 CAD controls .When the CAD cases and controls were divided into subgroups by gender or hypertension, the association between rs9943582 and overall CAD remained non-significant (Table 2), we observed significant association between rs9943582 and LVSD in the CAD population (Table 5). In 431 CAD patients with LVSD, the frequency of minor allele A was 0.34. In 1,046 CAD patients with normal LVEF (>50%), the frequency of allele A was 0.26. The observed allelic P-obs for association was 3.19×10–6 with an observed OR of 1.50 (95% CI = 1.27–1.78) (Table 5). After adjusting for covariates of gender, age, smoking, hypertension, diabetes and lipids concentrations  by multivariate logistic regression, the association remained significant with P-adj = 6.71×10–5 and an adjusted OR of 1.43 (95% CI = 1.20–1.70). The empirical P value for the association was estimated to be 8.00×10–6 (Table 5).When we divided the CAD patients into a CAD sub-group with LVSD (n = 431) and a CAD sub-group with normal LVEF  (Table 5). In the male CAD group contained 259 LVSD cases and 634 controls with normal LVEF, P-obs was 0.02 and P-adj was 0.04. In the female CAD group contained 172 LVSD cases and 412 controls with normal LVEF, P-obs was 1.05×10–5 and P-adj was 1.63×10–5. SNP rs9943582 showed more significant association with LVSD in CAD patients without hypertension than in the CAD group with hypertension (Table 5). In the CAD group with hypertension , P-obs was 1.18×10–3 and P-adj was 2.33×10–3. In the CAD group without hypertension , P-obs was 1.20×10–3 and P-adj was 4.98×10–6 (Table 5).Considering that sex and hypertension affect the outcomes of heart failure associated with CAD, we divided the study population into subgroups, including the male group, the female group, a group with hypertension or a group without hypertension. SNP rs9943582 showed more significant association with LVSD in female CAD patients than in the male CAD group (P = 0.07) or by hypertension (Table 5).We compared the homogeneity of ORs between different sub-groups to analyze whether rs9943582 interacted with gender or hypertension using a Breslow-Day test, but detect no significant differences between subgroups divided by gender , left atrium size  and LVEF , but not with thicknesses of the interventricular septum (P = 0.33), LV thickness of the posterior wall (P = 0.61) and the diameter of the aortic root (P = 0.61) (Table 6).Using linear regression, we assessed the association of rs9943582 with echocardiographic parameters. In the CAD patients with LVSD, rs9943582 showed significant association with LV diastolic internal dimension  and LVEF , but not with other echocardiographic parameters (Table 6).In the CAD patients with normal LVEF, the association was observed between rs9943582 and LV diastolic internal dimension . For LVEF, significant association was found in all sub-groups (Table 6).We also divided both LVSD and normal LVEF groups into subgroups by gender and hypertension and performed association analysis between rs9943582 and echocardiographic parameters in different groups. In CAD patients with LVSD, significant association was found between rs9943582 and LV diastolic internal dimension, left atrium size and LVEF the in male, female, hypertension and non-hypertension subgroups. In CAD patients with normal ventricular function, significant association was found between rs9943582 and LV diastolic internal dimension only observed in the female group and in CAD patients with hypertension  (Table 7).Genotypic association between rs9943582 and CAD or LVSD was performed, and the results are shown in P-obs of 8.98x10-4 and 1.22×10–3, respectively (Table 7). The association remained significant after adjusting for covariates of age, gender, smoking, hypertension, diabetes mellitus and lipid concentrations with P-adj of 1.80x10-5 and 8.98x10-5, respectively (Table 7).In the population with 431 CAD patients with LVSD and 1,046 CAD with normal LVEF, significant association was found between SNP rs9943582 and LVSD under both dominant and additive models with APLNR gene encoding the apelin receptor and LVSD in humans. We found that the rs9943582 variant in the 5’-untranslated region of APLNR conferred a significant risk of LVSD among CAD patients (Table 6). A previous study showed that rs9943582 regulated APLNR transcription by affecting the binding of Sp1 transcription factor to the APLNR promoter, and that the A allele of rs9943582 had lower binding affinity to Sp1 and decreased transcriptional activity than the G allele [APLNR and the Apelin gene [APLNR in myocardium under ischemia/hypoxia injury. Carriers of the G allele, which have more transcriptional activity, may response more effectively to ischemia than carriers with the A allele, and receive more protection from myocardial dysfunction.Studies in animal models revealed that the apelin /APJ pathway was important in maintaining the contractile or overall function of the heart. Studies showed that in an isoproterenol-induced model of heart failure, LVSD was partially rescued by co-administration of apelin . More inG allele . Others lin gene ,26. One In vivo animal modeling or in vitro studies showed that expression of endogenous apelin and the APJ receptor was increased immediately after the myocardium was under hypoxia stress, and this up-regulation was confirmed to have a protective effect on the cardiomyocytes from apoptosis or injury [The apelin or APJ receptor is a G-protein-coupled receptor (GPCR) with seven transmembrane domains, and has sequence homology with the angiotensin II type 1 receptor (AT1) ,11. The r injury ,29,30. Ir injury ,31,32. Ur injury . Thus, uSeveral studies also showed that the APJ receptor and apelin were associated with atherosclerosis ,34. HoweAPLNR gene was associated significantly with left ventricle systolic dysfunction in patients with CAD. These results suggest that the apelin/APJ system is involved in the pathogenesis of heart failure in humans, and provide important insights into the genetic basis and biological pathways for heart failure. Future comprehensive genetic analysis by genotyping and analyzing more SNPs in the APLNR gene and other genes in the apelin/APJ pathway as well as haplotype analysis may further define the role of the apelin/APJ pathway in the pathology of heart failure.In conclusion, for the first time we show that the allele A of rs9943582 (-154G/A) in the


Contrast echocardiography is a technique that improves endocardial demarcation and provides real-time data on blood circulation . Left ventricle imaging study using contrast agents that cross the pulmonary circulation allows an improved visualization of endocardial tissue. This creates a more accurate ultrasound evaluation of left ventricular dimensions and its kinetics. Contrast echocardiography can improve Doppler mode evaluation and can provide information on myocardial perfusion precisely through this mechanism.Microbubble contrast agents are second-generation ultrasound contrast agents and are especially useful in endocardial demarcation. Second generation ultrasound contrast agents available now, include “Definity”, “Optison” - available in almost all countries with an average medical system except for Europe and “SonoVue” - available in most European countries. Contrast agents are represented by microbubbles between 1-10μm in diameter, containing a gas surrounded by a phospholipid membrane (SonoVue) or protein (Optison).Because the microbubble ultrasound characteristics used are different from the characteristics of the surrounding tissue or blood elements and cardiac structures, their diffusion produce very strong acoustic signals, which are directly proportional to blood volume. Quantitative assessment of myocardial microcirculation is now possible due to the advancing techniques in contrast echocardiography, provided that the left ventricular cavity has an increased echogenicity compared with the surrounding myocardium (which has a lower blood volume). Contrast Agents1]. The main types of contrast agents, and their characteristics are presented in Table 1 [2]. Echogenicity and properties of second-generation ultrasound contrast agents are determined by the size of the microbubbles, the type of encapsulated gas, and the type of the material that forms the microbubbles (lipid or protein) which is different for every contrast agent. The ultrasonic properties of these microbubbles are different from the ultrasonic properties of blood cells and myocardial tissue and represent a characteristic function of nonlinear oscillation, which means they will reflect ultrasound not only at the fundamental frequency characteristic for the ultrasound source, but with a considerable increase of the frequency. In general, the more elastic the microbubble wall, the more tissue oscillation will be generated, so the ultrasound image will be improved. In contrast, microbubbles with a thin membrane can break when exposed to an environment with high intensity ultrasound signal ; - In order to increase and improve endocardial visualization and evaluation of left ventricular structure and function when two or more segments are not well viewed in routine ultrasound examination . The real time assessment of myocardial perfusion is possible by using contrast echocardiography with second generation agents, because the size of these microbubbles is comparable to the size of a red blood cell (1-10 microns) and can penetrate the microcirculation up to the distal capillary [3] .b) 4].Recent studies have found that the information and data accuracy obtained by using contrast echocardiography are similar with those offered by nuclear scintigraphy. Initial studies have shown that there is a good correlation between contrast echocardiography and regional imaging - SPECT (single photon emission computed tomography) in patients with coronary artery disease, but later it turned out that the myocardial contrast echocardiography obtained during exercise or other types of vasodilation inducing technique could bring additional data on the location of the affected area compared to SPECT . The use of contrast echocardiography in the evaluation of myocardial perfusion after primary angioplasty has a predictive value on outcome, concerning the efficiency of the revascularization in the left ventricle. The evaluation of myocardial perfusion in coronary microcirculation by contrast echocardiography is correlated with coronary flow reserve, evaluation that can also be performed by pulsed Doppler measurements [7].In patients with acute myocardial infarction, contrast echocardiography performed before angioplasty can show the tissue at risk and, performed 24 hours after surgery (angioplasty), can identify the area where revascularization does not occur [8]) of 50 patients who had myocardial infarction and received thrombolytic therapy, showed. The presence of lower intensity opacities (hypoechogenic) on the contrast echocardiography image, that have been performed on the second day after the administration of thrombolytic therapy, correlated with a higher recurrence of a heart attack or other severe heart pathologies  in the near future, on an average of 22 months from the first cardiovascular event . In another study, patients with a persistent defect in the infarct area due to unrecovered myocardial perfusion had regional or global systolic dysfunction .Contrast echocardiography can provide prognostic data, as a survey  and underwent stent angioplasty in coronary care centers in the first 6-12 hours from the onset of the acute symptoms. These were clinically assessed in a timeframe of 1-6 months post-infarction, and by ultrasound, including contrast echocardiography with contrast agent Sono-Vue (sulfur hexafluoride) by using Philips I33 system with the “Low IM” - low mechanical index program.Fig. 3). On admission, the T troponin was 8 times higher than the 99th percentile, mild leukocytosis was present, blood glucose level was 118mg/ dl, slightly elevated LDL cholesterol (198mg/ dl), serum triglycerides were 180 mg/ dl, and C-reactive protein - 0.5 mg/ dl. Left ventricular ejection fraction on echocardiography was 45-50% with a kinetic disorder in the posterior inferior ventricular wall - 5 of 17 segments with a 1.35 kinetics index.The patient RV aged 57 years old, obese, with modified fasting plasma glucose, presented an acute inferior ST elevated myocardial infarction. Approximately 6 hours after the symptomatic onset, the patient was evaluated in an intensive coronary care unit by coronary angiography. The investigation revealed right coronary artery occlusion, and stent angioplasty was successfully performed, with post-procedural TIMI 3 flow ; Ejection fraction measured by the Simpson method in apical 4 chamber and 2 chamber view was 53% . Left ventricular diastolic dysfunction with impaired relaxation pattern without mitral regurgitation without pulmonary hypertension was also present.A month after angioplasty, the patient was hemodynamically stable, with no angina, and was hospitalized for clinical and paraclinical assessment. Routine echocardiography and contrast echocardiography with Sono-Vue contrast agent (continuous intravenous injection - 1ml/ min for 3 minutes) were performed, showing reduced systolic parietal thickening of the myocardium on the posterior wall of the left ventricle, with a parietal kinetic score of 20 and a kinetic index of 1.17  , this preset is used as microbubbles in the sound field strongly represented by IM> 0.5 being destroyed.Fig. 5. The semiquantitative evaluation of the myocardial perfusion was performed by using the 17-segment model used in kinetic score and by evaluating the rate of contrast agent uptake in myocardial segments. The absence of the myocardial uptake was quantified as 0, heterogeneous or reduced uptake by 1 and the normal uptake was quantified by 2. The myocardial perfusion index was calculated as the sum of the scores of every segment divided by the total number of segments . The myocardial perfusion score in this case was 30 and the myocardial perfusion index was 1.74.The study of myocardial perfusion showed a perfusion defect through the absence of the acoustic signal in the lower one third of the left ventricular wall, and a scratchy aspect in the middle third of the left ventricular wall after the destruction of the microbubbles with a strong signal (flash), and study of myocardial capillaries refill during continuous intravenous injection with SonoVue (1 ml/ min) - 2]. The level of contrast homogeneity correlates with myocardial viability and recovery of myocardial function . In a patient with acute myocardial infarction efficiently revascularized in the therapeutic “window”, one month after the myocardial infarction, reperfusion was absent in the affected territory due to the impairment of microcirculation integrity, as evidenced by myocardial unopacified risk area. Therefore, myocardial recanalization was not followed by myocardial reperfusion. The information is useful in therapeutic management both on the short, medium, and long term [13].Contrast echocardiography is a technique that improves endocardial tissue evaluation by ultrasound and can be used to enhance the Doppler evaluation and to assess the myocardial perfusion [Left ventricular cavity ultrasound opacification by using microbubbles contributes to a more precise delineation of endocardial tissue and decreases variability in the detection of left ventricular wall motility abnormalities and ejection fraction analysis.Microbubble contrast agents can be used to assess myocardial perfusion in stress and rest echocardiography. The prognostic value of myocardial perfusion study was proven by studies that have evaluated post-myocardial infarction recovery after revascularization maneuvers.


To investigate the relationship between cardiac diastolic dysfunction and outcomes in patients with pulmonary arterial hypertension (PAH) and to clarify the potential effect of two-dimensional echocardiography (2D-echo) on prognostic value in patients with PAH.Patients diagnosed with PAH (as WSPH (World Symposia on Pulmonary Hypertension) classification I) confirmed by right heart catheterization (RHC), received targeted monotherapy or combination therapy. 2D-echo parameters, World Health Organization (WHO) functional classification and 6-minute walking distance (6MWD) were recorded. The clinical prognosis of patients was assessed by the correlation between echo parameters and clinical 6MWD using receiver operating characteristic (ROC) curve analysis.LVDD  = −0.699; rRVDD  = −0.818, both P<0.001) and at last follow-up . Furthermore, bi-ventricular (LVDD+RVDD) scores measured by 2D-echo had a better correlation with 6MWD at baseline and last follow-up . ROC curve analysis showed that the area under curves (AUCs) for LVDD score, RVDD score and (LVDD+RVDD) scores were 0.823 (P<0.0001), 0.737 (P = 0.0002), and 0.825 (P<0.0001), respectively. Compared with ROC analysis of other single parameters, cardiac diastolic function score was more accurate in predicting survival in patients with PAH.Fifty-eight patients were included. Left and right ventricular diastolic dysfunction (LVDD and RVDD) scores measured by 2D-echo had good correlation with 6MWD at baseline  scores yielded a comprehensive quantitative assessment of LV and RV diastolic function that correlated moderately with clinical functional parameters and might be useful in the assessment of PAH. Echocardiography (echo) is used mainly for preliminary screening in patients with suspected pulmonary arterial hypertension (PAH). In the absence of right ventricular (RV) outflow tract obstruction, systolic pulmonary artery pressure (SPAP) is estimated from the RV systolic pressure . Recently, echo parameters have been used to evaluate RV function, by tricuspid annular plane systolic excursion (TAPSE) th WSPH - patients were required to have confirmed WSPH classification I. Exclusion criteria were WSPH- I with atrial fibrillation and other irregular rhythm, WSPH-II, III, IV, and V pulmonary hypertension (PH), or non-PH. Regarding 2D echo, the image data obtained from the patients with rhythm abnormalities would not be available and accurate. According to 5th-WSPH Between January 2008 and December 2011, we prospectively studied 58 consecutive patients aged 18 to 78 years. All patients underwent clinical evaluation, including hematological examination , electrocardiogram (ECG), chest radiography, pulmonary function test, high resolution CT (HR-CT) scan, and 6MWD on the same day that they also underwent echo evaluation. RHC was performed within 48 hours of echo examination. Inclusion criteria were mean pulmonary arterial pressure (MPAP) >25 mm Hg, pulmonary arterial wedge pressure (PAWP) ≤15 mm Hg, and pulmonary vascular resistance (PVR)>3 Wood units (under RHC). Diagnosis of PAH was based on criteria from the 5Echo imaging was performed in all study participants in the left decubitus or supine position using a GE vivid E9 equipped with a M5S transducer . In the first instance, two-dimensional (2D) and Doppler images were acquired using the MS5 transducer. To ensure inclusion of the entire left and right ventricles within the pyramidal scan volume, all echo datasets were acquired using the wide-angled full-volume mode over three consecutive cardiac cycles during a single breath-hold. Three datasets were obtained for each patient. Echo recordings and measurements were performed according to the American College of Cardiology Foundation (ACCF)/American Society of Echocardiography (ASE) appropriate use criteria m), mitral valve peak A velocity (Am), the Em/Am ratio and deceleration time (DTm) of mitral valve peak E. PW tissue Doppler imaging (DTI) was performed to acquire mitral annular velocities by setting the sample point at the lateral and septal sides of the mitral annulus. Measurements included the mitral annular lateral peak systolic velocity (Sm′), mitral annular lateral e velocity (em′), lateral a velocity (am′); mitral annular septal systolic velocity (Ss′), septal e velocity (es′) and septal a velocity (as′) (t), tricuspid valve peak A velocity (At), the Et/At ratio, and deceleration time (DTt) of tricuspid valve peak E velocity, were recorded by PW Doppler at the level of tricuspid leaflet tips with the help of color flow imaging for optimal alignment of the Doppler beam. DTI of tricuspid annular velocity measurements included tricuspid annular peak systolic velocity (St′), tricuspid annular lateral e velocity (et′) and lateral a velocity (at′)  diameter and its collapse during inspiration under long-axis subcostal views Standard views from the parasternal long and short axis and apical four-chamber views were used ty (as′) . Additioty (at′) . TAPSE wty (at′) . RVSP wam′, es′, Em/Am, Em/em′, DTm, LAVI. LV diastolic function was divided into: normal, mild or grade I (impaired relaxation pattern), moderate or grade II  and severe or grade III (restrictive filling) by integrated analysis of multiple LV diastolic parameters t/At, Et/et′ and DTt. Similar to LV diastolic function, RV diastolic function was graded and assigned a score as follows: normal (score  = 1), grade I , grade II , grade III .Measurement of cardiac morphology and function indicators included: left atrial (LA) diameter, left ventricular (LV) internal diameter, left atrium volume index (LAVI), LV ejection fraction (LVEF), right atrial (RA) diameter, RV internal diameter, RV end-diastolic volume (RVEDV), RV end-systolic volume (RVESV), RV stroke volume (RVSV), and RV ejection fraction (RVEF). According to ASE guidelines, the varying severity of LV diastolic dysfunction is reflected by all six conventional measures of LV filling, including e2 was monitored continuously with a wireless pulse oximeter. The following data were recorded: total distance walked (expressed in meters), SpO2, blood pressure and heart rate before and after the test. The Borg dyspnea scale was assessed in conjunction with the 6MWD Test.The 6MWD Test was conducted according to American Thoracic Society guidelines All patients were treated with targeted therapies including endothelin receptor antagonists (ERA), phosphodiesterase type-5 inhibitors (5-PDEI), and prostacyclins, in addition to conventional drugs according to current guidelines All patients were followed-up via an outpatient clinic or hospitalization every 6 months ±2 weeks. The deadline of the last visit of the last patient was 30 June 2013. Patients underwent echo, 6MWD Test, as well as WHO functional classification and Borg dyspnea scale evaluation during every follow-up. Major adverse events, including death, lung transplantation, and heart-lung transplantation, were recorded.Normally distributed continuous variables were presented as mean ± SD. The Student's t test was used to compare values of clinical and echo parameters between baseline and the last follow-up. The degree of agreement between two modalities was assessed using the methods of Pearson's correlation coefficient  Demographic and clinical characteristics of all patients enrolled in this study are shown in As presented in The mean duration of follow-up for all 58 patients was 28.3±16.1 months. Seventeen patients died and 1 underwent lung transplantation during a mean total duration of 28.3±16.1 (range 6 to 70) months of follow-up. The main adverse events occurred at an average of 20.9±11.7 months in 18 patients. The mean follow-up duration for the other 40 patients with PAH was 31.7±16.8 months. All data, including WHO functional class, Borg dyspnea scale, 6MWD, and parameters of 2D-echo of all 58 patients were recorded at the last follow-up .LVDD  = −0.699 (P<0.001) at baseline and rLVDD  = −0.701 (P<0.001) at last follow-up, respectively  and last follow-up  with 6MWD were significant (RV diastolic scores and other echo parameters collected at baseline and last follow-up are listed in nificant .LVDD+RVDD  = −0.831 (P<0.001) at baseline and rLVDD+RVDD  = −0.771 (P<0.001) at last follow-up, respectively , RV Tei index , FAC  with 6MWD were statistically less significant .SPAP  = 0.780, P<0.0001; AUCDPAP  = 0.790, P<0.0001; AUCMPAP  = 0.807, P<0.0001; AUCCO  = 0.649, P = 0.0812; AUCPVR  = 0.838, P<0.0001, respectively  had more accurate and significant value for predicting the clinical prognosis of patients with PAH than most single echo parameters such as Em, Em/Am, Se′, Et, At, et′, Et/At, Et/et′, DTt, TAPSE, Tei and FAC. Further analysis showed that bi-ventricular diastolic function scores (LVDD + RVDD scores) were more predictive than single ventricular diastolic dysfunction scores (LVDD score or RVDD score) .Data for the area under the ROC curve for hemodynamic parameters of RHC  evaluating the clinical prognosis of patients with PAH were: AUCectively . Among tD score) , Fig. 6.m, Am, Em/Am, DTm, em′, Em/em′, am′, Sm′). Each parameter emphasizes a different aspect of LV diastolic function in PAH. It is well known that no single echo parameter is capable of accurately discriminating between normal and various levels of severity of LV diastolic dysfunction, because most indicators are influenced by multiple factors, including myocardial compliance and stiffness, LV systolic function and cardiac rhythm Clinicians have paid increasing attention to the impairment of LV diastolic function in patients with PAH. However, there is no direct measure of LV stiffness and relaxation function and no accepted comprehensive evaluation index of LV diastolic function. The present studies Although echo is a recommended screening test for pulmonary hypertension, its limited sensitivity and only moderate correlation with invasively-determined SPAP are notable limitations et al. demonstrated that improvement in Tei index but not TAPSE and FAC correlated with improvements of PVR during the clinical course in patients with PAH. However, Tei index did not significantly correlate with 6MWD at follow up In recent years, in order to assess right heart function in patients with PAH and to further predict the clinical prognosis of patients with PAH, TAPSE mIn this study, we created new indices of cardiac diastolic functional classification  to comprehensively assess the clinical prognosis of patients with PAH. This is the first study to use quantitative grades of ventricular diastolic function to evaluate clinical outcomes of patients with PAH, and the results show significant correlations between the quantitative scores of ventricular diastolic function score  and 6MWD. In our study, as well as others Several study limitations should be pointed out. First, this study had no control group. Second, our results should be confirmed in a larger study population. Our study included heterogeneous causes of WSPH-I, with a variety of treatments and follow-up periods. In addition, because of the small sample population and too many risk factors, we could not perform subgroup analysis and uni- and multivariate logistic analysis. Third, in our study, as well as others Single ventricular diastolic function score was superior to single parameters measured by 2D-echo for predicting clinical prognosis in patients with PAH, and bi-ventricular diastolic function scores were better than single ventricular diastolic function score for predicting clinical outcomes in patients with PAH. LVDD/RVDD/LVDD+RVDD score yielded a comprehensive quantitative assessment of LV/RV diastolic function that correlated moderately with clinical functional parameters and might be useful in the assessment of PAH.


T1 mapping and ECV imaging are promising diagnostic tools in patients with suspected myocarditis. However, there are currently no data on the potential influence of slice orientation on the derived T1 and ECV values. Thus, we compared global myocardial T1 and ECV values between slices with short and long axis orientation.This study included 50 patients with clinically suspected myocarditis, who underwent CMR at 1.5 Tesla. T1 quantification was performed on three short  and on three long axis slices , respectively. The modified Look-Locker inversion-recovery (MOLLI) sequence was used before and 15 minutes after administration of 0.075 mmol/kg Gadolinium-BOPTA. Native T1, post-contrast T1 and extracellular volume (ECV) maps were calculated using a dedicated plug-in written for the OsiriX software. Mean native and post-contrast T1 as well as ECV were obtained from the three short and long axes, respectively.There were significantly lower median native myocardial T1 values on long axis slices (1079 (1040-1130.0)) compared to short axis slices (1103 (1069-1140); p=0.0026). However, there were no significant differences in post-contrast myocardial T1 values (median 554 (505-596) vs. 555 (509-601); p=0.2299) or ECV (median 30 (27-33) vs. 29 (26-33); p=0.6063) between short and long axis slices, respectively.Slice orientation could be a potential confounding factor for the assessment of native global myocardial T1 values in myocarditis. Possible explanations for this finding include technical issues, such as variations in through-plane motion or partial-volume effects related to slice orientation, but also the heterogeneity of myocardial injury in myocarditis. However, our data indicate that global myocardial ECV values could be less sensitive to slice orientation.


However, imaging murine hearts presents significant challenges due to their small size and rapid heart rate. Here we demonstrate the feasibility of high-frame-rate, noninvasive optoacoustic imaging of the murine heart. The temporal resolution of 50 three-dimensional frames per second provides functional information at important phases of the cardiac cycle without the use of gating or other motion-reduction methods. Differentiation of the blood oxygenation state in the heart chambers was enabled by exploiting the wavelength dependence of optoacoustic signals. Real-time volumetric tracking of blood perfusion in the cardiac chambers was also evaluated using indocyanine green. Taken together, the newly-discovered capacities offer a unique tool set for  Human cardiac diseases are linked to many inheritable and environmental factors, but the link between molecular- and organ-level dysfunction remains unclear. As more primary causes of cardiovascular disease are identified, the need to characterize their functional effects and therapeutic responses is growing. Many transgenic and surgical mouse models have been developed to better understand a wide variety of cardiac diseases identified in humans, such as models of inheritable cardiomyopathies, diseases related to chronic ventricular afterload, myocardial infarctionex vivo, utilizing the Langendorf perfusion methodin vitro and in situ methods. Relatively recent developments in biomedical imaging have allowed for in-vivo characterization of organ-level function by cardiac ultrasound456891112Charaterization of cardiac function in such models is often performed In-vivo imaging at high spatial resolution can be achieved by magnetic resonance microscopy (MRM), which can be used to visualize even small embryonic mouse hearts15161819ex-vivo (e.g. Langendorf) methods to reach the heart. Lastly, optical coherence tomography methods can also provide high spatio-temporal images in 4D, but are similarly limited to surface-level investigations222324The small size of the mouse heart additionally requires a high-resolution imaging platform to provide robust volumetric analyses. in-vivo and in an intact heart. By relying on detection of light-induced pressure variations, optoacoustics benefits from both high spatio-temporal resolution of ultrasound and contrast-related advantages of light illuminationOptoacoustic imaging holds multiple prospective advantages for cardiac imaging as it: (1) provides high spatial and temporal resolution; (2) possesses optical contrast, and hence can be used in combination with a large selection of optical contrast agents to target molecular level dysfunction, and; (3) has the advantage of deeper penetration, allowing for imaging of cardiac function truly Here we demonstrate, for the first time to our knowledge, optoacoustic visualization of fast beating mouse heart in three dimensions rendered at a high frame rate of 50 volumetric images per second. Furthermore, by sequential acquisition of data at several excitation wavelengths, we were able to differentiate blood oxygenation levels in the heart chambers based on spectral dependence of the optoacoustic data. Finally, high-temporal-resolution tracking of blood flow in the heart has been made possible by visualizing the distribution of intravenously-administered indocyanine green optical contrast agent.in vivo imaging, the mouse was placed in a prone position over the active surface of the ultrasound detector array, as indicated in o solid angular coverage of the spherical array probe in our case) also affect the visibility of the lateral sides of the heart. Finally and importantly, the highly absorbing blood in the heart chambers causes significant light attenuation, leading to strong bias toward structures at the myocardium surface. Each of these factors contributed to the limited volume of the heart which can be efficiently visualized with our optoacoustic system.For z direction for the three-dimensional data. In an attempt to quantify cardiac dynamics, the optoacoustic signal was traced over time at two locations, corresponding to the left atrium and left ventricle, indicated respectively by P1 and P2 in The potential for visualizing fast cardiac cycle dynamics was demonstrated by acquisition of optoacoustic images at 50 Hz. t) to peak values of ICG absorbance in the RV and the LV can be estimated. For this, 1000 different VOIs in the right and left ventricles were considered. An average value of Δt = 1.24 seconds for all VOIs was subsequently obtained, where the uncertainty in Δt amounted to a standard deviation of s(Δt) = 0.35 seconds. Physiologically, this parameter describes the time it takes for blood to travel through the pulmonary circulation (from the RV to the LV) and is referred to as pulmonary transit time.Volumetric tracking of blood perfusion was showcased with injection of indocyanine green (ICG) as described in the methods section. Four representative time instants corresponding approximately to the same phase of the cardiac cycle are shown in in vivo. Versatility of the system in resolving functional and, potentially, molecular contrast is enabled via fast acquisition of images at multiple excitation wavelengths. In this way, the basic cardiac functional analyses were derived here from the intrinsic spectral dependence of oxy- and deoxy-hemoglobin as well as extrinsically-administered ICG. The heart chambers were distinguished based on the basic analysis of spectral dependence of the optoacoustic signals in the respective regions of interest. Determination of additional intrinsic functional parameters, such as blood oxygen saturation levels, would necessitate development of more sophisticated processing methods to efficiently register images at the different wavelengths and accurately account for the wavelength-dependent light fluence distribution across the moving heart.The results presented herein showcased the unique capability of four-dimensional optoacoustic tomography for studies of cardiac dynamics with high spatio-temporal resolution necessary for characterizing the fast beating mouse heart In this work, we additionally demonstrated high temporal-resolution tracking of blood flow in the heart by visualizing the distribution of ICG following intravenous injection. Due to the adequate penetration of optoacoustics, these measurements were possible non-invasively, without the need to open the chest of the animal. The pattern of blood flow determined in the ICG experiment was consistent with the expected blood flow within the heart, where blood first enters the right chambers and subsequently reenters (after circulating through the lungs) the left chambers of the heart. The dynamic imaging of blood circulating through the heart may allow for a better understanding and diagnosis of cardiovascular disease. One potential application would be diagnosis of ventricular dysfunction, which would be expected to affect the delivery of ICG signal from the right to the left ventricle. In the current study, we were able to resolve the pulmonary transit time, which may serve as a useful indicator of ventricular dysfunction, although further studies are required to determine whether the changes in this parameter in health and disease surmount the uncertainties in the measurements. Such an approach could also potentially characterize left ventricular dysfunction as a delay in the ICG signal within the LV, and accumulation of the ICG signal in the pulmonary veins. ICG signal within the lungs may further serve as an indicator of cardiogenic pulmonary edema, allowing for diagnosis and characterization of the disease progression. Another value may be found in the characterization of cardiac valve function, where, as an example, a slow but periodic increase in the ICG signal from the LV might indicate a leaky aortic valve. As a result, this system indicates the potential for use of optoacoustics as a hand-held clinical imaging system for the human cardiovascular system, though its applicability will mainly depend on the technical progress with achieving deeper optical penetration through highly absorbing blood. In this regard, improvements in the probe design and light delivery strategies may greatly benefit the clinical translation efforts of the cardiac optoacoustic imaging technology. Furthermore, other externally-administered contrast agents can be potentially targeted to molecular events to characterize underlying mechanisms of cardiac diseases. In the pre-clinical setting, such approaches would be useful in determining the efficacy of treatments of heart disease, e.g. myocardial-infarction-associated inflammation, cell death, or remodeling of the myocardium. Finally, optoacoustic imaging at high temporal resolution may have other physiological applications, such as the determination of ventricular function and hemodynamic analysis.o of solid angular coverage around the illuminated side of the heart. Thus, indirect contributions from ultrasound waves affected by the lungs are largely avoided in the image reconstruction procedure.From the technical point of view, the presented 3D tomographic configuration provides nearly isotropic three-dimensional spatial resolution in the range of 200 μm3133In conclusion, we have shown the capabilities of volumetric optoacoustic cardiac imaging at an unprecedented time resolution. In combination with its unique advantages of high spatial resolution and functional and molecular optical contrast, the presented cardiac imaging approach anticipates a broad range of applications that require fast dynamic visualization of entire volumes currently unfeasible with other imaging modalities. Future experiments are tailored to provide functional and molecular assessments of healthy and diseased conditions of the mouse heart induced by transgenic or surgical means.The lay-out of the experimental setup is depicted in 35An adult wild-type male CD1 mouse was used in the experiments. The hair in the chest area was removed with a shaving lotion . The mou3 with a parallel implementation of a back-projection formula, as described elsewhereThe 256 optoacoustic signals corresponding to each frame consist of 2030 time samples acquired at a rate of 40 megasamples per second. The signals are first deconvolved with the impulse response of the individual piezoelectric elements  and subsequently band-pass filtered with cut-off frequencies between 0.1 and 7.5 MHz. Three-dimensional images are reconstructed for a volume of interest of 14 × 14 × 12 mmHow to cite this article: Deán-Ben, X. L. et al. High-frame rate four dimensional optoacoustic tomography enables visualization of cardiovascular dynamics and mouse heart perfusion. Sci. Rep.5, 10133; doi: 10.1038/srep10133 (2015).


Echocardiography is the standard method for assessing myocardial function in patients with ischemic heart disease. The acquisition and interpretation of echocardiographic images, however, remains a highly specialized task which often relies entirely on the subjective visual assessment of the reader and requires therefore, particular training and expertise. Myocardial deformation imaging allows quantifying myocardial function far beyond what can be done with sole visual assessment. It can improve the interpretation of regional dysfunction and offers sensitive markers of induced ischemia which can be used for stress tests. In the following, we recapitulate shortly the pathophysiological and technical basics and explain in a practical manner how we use this technique in investigating patients with ischemic heart disease. Assessing the impact of ischemic heart disease on cardiac function is one of the key tasks of routine clinical echocardiography. At virtually any stage of the disease process, echocardiography is of diagnostic or prognostic value, guiding further therapeutic decisions. The careful observation of global and regional ventricular function and morphology in resting images, allows describing and distinguishing acute ischemia, scar and infarct related remodeling while stress echocardiographic methods may be used to assess the severity of coronary stenosis or to identify viable myocardium. Offering this wealth of information, echocardiography has become an indispensable tool in managing patients with coronary artery disease.The acquisition and interpretation of echocardiographic images, however, remains a highly specialized task which requires knowledge, skills and experience. Not all echocardiographic parameters are quantifiable. Moreover, typical echocardiographic tasks, such as the evaluation of regional myocardial dysfunction in ischemic heart disease, rely entirely on the subjective assessment of the reader and require therefore particular training and expertise –4.Tissue Doppler and speckle tracking based myocardial deformation imaging allows quantifying myocardial function far beyond what can be done with sole visual assessment. In the following, we would like to explain how we use this technique in investigating patients with ischemic heart disease.−1]. In clinical use, the complex three-dimensional deformation of the heart is commonly described by either its longitudinal (LS), circumferential (CS) or radial strain (RS) components . There are two main echocardiographic modalities for the assessment of myocardial deformation: tissue Doppler imaging (TDI) or speckle-tracking imaging (STI)  or “post-systolic thickening” is a sensitive and specific feature of developing ischemia if a normal baseline examination is available , 23. If Patients with myocardial damage after myocardial infarction will usually present changes in global and regional function, both of which need to be described and followed. In these patients, a speckle tracking based analysis can be most easily integrated in the clinical routine.Three standard grey scale image loops, with settings balanced for both spatial and temporal resolution (ca. 40–80 frames per second), covering the LV and including the mitral and aortic valve should be stored. Care must be taken that the LV is not foreshortened and that reverberation artefacts  on the edges of the image sector are avoided. A clear artefact free display of the apex is desired. We acquire three consecutive heart beats, avoiding extrasystoles. In addition, a PW- or CW-Doppler trace of the LVOT is useful to obtain timing information.First, the four- and two-chamber images are analyzed with an automated, tracking based EF measurement algorithm. Depending on the software used, this can be fully automatic or semi-automatic with the user indicating the initial endocardial contour. Care must be taken to check the tracking quality, i.e. how well the tracking line follows the endocardial motion. Software which do not allow this step should not be used. This procedure results in a set of volumetric measurements  which is reported in the protocol of the examination Figure .SecondlyThis is usually an emergency room scenario where an immediate coronary intervention has highest priority. The echocardiographic examination should therefore be limited to the necessary minimum which is needed to clarify remaining clinical questions. Conclusions will be usually drawn from the immediate visual analysis of the image data.A documentation of the three apical views is a matter of seconds and should be attempted. It allows a later off-line speckle tracking based analysis as described above, which can serve as baseline investigation to follow the course of the patient Figure .Figure 4Ischemia testing aims at detecting transient regional dysfunction during an exercise or pharmacological stress which requires training and experience –4. FunctTissue Doppler strain is robust for shape analysis, quickly analysable during data review and can easily deal with high heart rates due to its excellent temporal resolution. It is therefore our preferred method during stress echocardiography. We use a machine which allows the simultaneous acquisition of grey scale and colour tissue Doppler data while only the grey scale image is displayed. Care must be taken that the underlying colour Doppler sector has the size of the full image, while the frame rate should not fall far below 100 fps. We acquire apical four-, three- and two-chamber views as they allow to measure longitudinal strain in all segments. We perform stress echos according to current recommendations . DobutamThe classical visual assessment of wall motion in a quad-screen display of baseline and different stress stages with synchronized replay is our standard approach Figure . In caseCurrent deformation imaging software is sufficiently developed to allow fast and reliable analysis and to provide clinically helpful answers. As any quantitative imaging technique, deformation imaging relies on the assumption that pathologic processes cause functional changes and that these changes can be visualized with sufficient accuracy. Improvements in both, tissue Doppler and speckle tracking algorithms would be desirable to reduce noise and improve measurement accuracy . If furtFrom a current perspective, strain and strain rate imaging by tissue Doppler and speckle tracking are helpful tools in the clinical assessment of CAD patients and should be part of every echocardiographic examination.