Myocardial native T1 measurements are likely influenced by intramyocardial blood. Since blood T1 is both variable and longer compared to myocardial T1, this will degrade the precision of myocardial T1 measurements. Precision could be improved by correction, but the amount of correction and the optimal blood T1 variables to correct with are unknown. We hypothesized that an appropriate correction would reduce the standard deviation (SD) of native myocardial T1.n = 400) referred for CMR with known or suspected heart disease were split into a derivation cohort for model construction  and a validation cohort for assessing model performance . Exclusion criteria included focal septal abnormalities. A Modified Look-Locker inversion recovery sequence  was used to acquire T1 and T1* maps. T1 and T1* maps were used to measure native myocardial T1, and blood T1 and T1*. A multivariate linear regression correction model was implemented using blood measurement of R1 (1/T1), R1* (1/T1*) or hematocrit. The correction model from the derivation cohort was applied to the validation cohort, and assessed for reduction in variability with the F-test.Consecutive patients  in both the derivation and validation cohorts respectively, suggesting that myocardial T1 measurements are influenced by intramyocardial blood. Mean myocardial native T1 did not differ between the derivation and validation cohorts . In the derivation cohort, correction using blood mean R1 and mean R1* yielded a decrease in myocardial T1 SD .Blood [LV + RV] mean R1, mean R1* and hematocrit correlated with myocardial T1 . This 13% reduction in measurement variability leads to a 23% reduction in sample size to detect a 50 ms difference in native myocardial T1.When the model from the derivation cohort was applied to the validation cohort, the SD reduction was maintained (39.3 ms, Correcting native myocardial T1 for R1 and R1* of blood improves the precision of myocardial T1 measurement by ~13%, and could consequently improve disease detection and reduce sample size needs for clinical research. Parametric pixel-wise mapping has been developed to quantitatively measure and image the longitudinal magnetic relaxation time T1) [ [1]. NatHowever, the normal myocardial blood volume (MBV) averages approximately 6% of the myocardium , 14. TheApproaches for correcting for myocardial blood volume have been reported , 22. ReiConsecutive patients referred for diagnostic CMR for known or suspected heart disease at Karolinska University Hospital, Stockholm, Sweden, were retrospectively enrolled between 2014-01-02 and 2015-08-07. Inclusion was terminated when a total of 200 males and 200 females were included, respectively. A total of 543 patients were assessed for eligibility. Exclusion criteria included focal septal myocardial pathologies, cardiac shunts, poor image quality or presence of cardiac tumors, see Fig. n = 77, mean age 49 ± 14 years, 49% males) were prospectively recruited between April 2014 and July 2015 through local advertising. None of the volunteers had any cardiovascular disease or diabetes. Five were on statins and one was on aspirin for primary prevention. All volunteers had a normal 12-lead ECG and all scans were reported as normal by experienced Level 3 CMR cardiologists. Imaging was performed on a 1.5 T MR scanner  and a 32-channel cardiac phased array receiver coil was used. The imaging protocol included cines, native T1 mapping, T2 mapping, Late Gadolinium Enhancement (LGE) and post-contrast T1 mapping. For this study, only the native T1 and T1* maps were analysed. Whole blood for venous hematocrit was drawn in all subjects by venipuncture and analyzed as routine clinical samples using a Sysmex XE-2100 hematology analyzer  [Healthy volunteers  .3, TR/TE = 37.05/1.19 ms, matrix size = 143x256 and field of view (FoV) 303x360 mm2.All patient CMR scans were conducted on a 1.5 T scanner  with a phased-array 18-channel body matrix coil together with a spine matrix coil. All patients were examined in the supine position. CMR scans assessing LV function used retrospectively electrocardiographically gated balanced steady-state free precession (bSSFP) cine imaging covering the entire LV. Typical imaging parameters included flip angle = 61°, voxel size = 2.0x2.0x8.0 mm2, parallel acquisition technique (PAT) factor 2, number of inversion 2, data window duration 163 ms. Operators were allowed to perform standard cardiac planning adjusting for patient size, rendering a range of phase encoding lines 136–158, and FoV 241–384 x 300–410 mm2.T1 maps were acquired using an electrocardiographically gated Modified Look-Locker inversion recovery (MOLLI) sequence  with a 5The healthy volunteers were imaged using a 5s(3s)3s MOLLI protocol. The acquisition parameters were: pixel bandwidth 977 Hz/pixel; echo time = 1.1 ms; flip angle = 35°; matrix size = 256x144; slice thickness = 6 mm. Motion correction and a non-linear least-square curve fitting were performed with the set of images acquired at different inversion times to generate a pixel-wise T1 map and T1* map.LV volumes, ejection fraction (EF) and myocardial mass were quantified using the SyngoVia Software, VA30 . Body surface area (BSA) was calculated with the Du Bois formula . VolumetX is the blood measurement of mean R1, mean R1* or hematocrit, mean is the mean for the patient cohort, and the constant was calculated as the slopes of linear regression between myocardial T1 and the blood measurements.A linear correlation between septal myocardial T1 and blood measurements was assumed. T1 was corrected using the equation, Equation 1:The T1 maps from the healthy volunteers were analysed using CVI42 software  by one observer. Global myocardial T1 values were acquired by carefully delineating the endo- and epicardial borders and eroding 10% to acquire the middle 80% of the myocardium. ROIs were drawn in the LV and RV blood pools of the mid-ventricular short-axis slice of the native T1 and T1* maps, and care was taken to avoid papillary muscles.p < 0.05.Continuous variables were reported as mean and SD. Statistical analysis was performed using Microsoft Excel , and statistical testing was performed using Statistical Product and Service Solutions® . Statistical significance was defined as t-test as appropriate in normally distributed data, and Mann–Whitney U-test in data with non-normal distribution. Sample size calculations were performed using Microsoft Excel.Multivariate linear regression was performed for slopes used for correction of native myocardial T1 for combinations of blood characteristics in the derivation cohort. The blood correction model from the derivation cohort was applied to the validation cohort, and the healthy volunteers respectively. The relationships between corrected and uncorrected native myocardial T1 values were investigated by the SD of the mean native myocardial T1, and evaluated for differences with the F-test. Mean values were compared by using the paired or unpaired p = 0.07) in the validation cohort, and 1027 ± 37.5 ms in the healthy volunteers. Hematocrit range for all 400 patients was 25 to 57%. There was no difference in characteristics between the derivation and validation cohorts, except for LV stroke volume (SV) and indexed LVSV (LVSVI), which was lower in the derivation cohort, albeit with a small magnitude of difference. There was no difference in characteristics between the females in the validation and derivation cohorts shown in Table Baseline characteristics of the derivation and validation cohorts are shown in Table All the blood measurements correlated with uncorrected native myocardial T1 in both the derivation and validation cohorts, see Table 2 0.26, p < 0.001), see Table p = 0.03) in the derivation cohort, see Fig. p = 0.049), see Fig. p < 0.001). The difference in mean myocardial T1 between males and females was eliminated by blood correction in the derivation cohort , see Fig. p < 0.001). The difference in mean myocardial T1 between males and females was reduced, but remained significant following blood correction, albeit by a small magnitude , see Fig. Multivariate linear regression in the derivation cohort showed that the best correction model was a combination of mean R1 and mean R1* (Rp = 0.85). The mean uncorrected myocardial T1 in the healthy volunteers was 1012 ± 30.4 ms for males and 1042 ± 38.0 ms for females (p < 0.001). The difference in mean myocardial T1 between males and females was eliminated by blood correction in the healthy volunteers .The SD of uncorrected myocardial T1 measurements of the healthy volunteers was 37.5 ms. The blood correction model for mean R1 and mean R1* did not decrease the SD . In the validation cohort, there was no difference in native myocardial T1 between patients with the thickest (>11.1 mm) and thinnest (<8.5 mm) myocardium .To ascertain if the partial-volume effect or hematocrit range contributed to the differences in native myocardial T1, the patients with the highest and lowest quartiles of wall thickness and hematocrit were examined in the derivation and validation cohorts, respectively. Patients with the thickest (>11.4 mm) and thinnest (<8.4 mm) myocardium had no difference in native myocardial T1 in the derivation cohort . There was also a difference in myocardial T1 in the validation cohort, between patients with the highest (>44%) and lowest (<37%) hematocrit . These differences disappeared following blood correction, in both the derivation cohort  and in the validation cohort .Patients with the highest (>43%) and lowest (<37%) hematocrit, differed significantly in myocardial T1 in the derivation cohort .We have demonstrated that correcting for blood characteristics decreases the variability of native myocardial T1 in a clinical population, and reduces gender differences in healthy volunteers. Blood correction was achieved by using the average of LV and RV blood (mean blood R1 and mean blood R1*), resulting in a 13% reduction in variability for native myocardial T1 measurements in the validation cohort. Correction for hematocrit did not provide an incremental reduction in SD beyond image-based blood characteristics. The use of the LV and RV blood highlights the feasibility of implementing an automatic blood pool mask , in ordeThere are several physiological factors that influence the variation of blood T1 values, such as hematocrit , sex 1010, age  and oxygFurthermore, Reiter et al.  showed tSeveral different methods to quantitatively measure T1 relaxation times are currently in clinical use . The oriFurthermore, T1 values differ over CMR magnetic field strength, both for blood and myocardium. Blood correction assuming linear correlation has been performed successfully at 3 T, however the changes in variability following blood correction were not evaluated . TherefoThe proposed validated blood correction method might have clinical significance for diseases that are characterized by a change in native myocardial T1 values, such as amyloidosis, iron-overload cardiomyopathy, Anderson-Fabry disease and other non-ischemic heart diseases. With increased diagnostic precision, these diseases could potentially be identified earlier when only subtle differences in the myocardial T1 may be present. The range of myocardial T1 values was decreased by 25% in the derivation cohort. This suggests that blood correction helps in determining the true biological variability in myocardial T1 values, making it easier to differentiate pathological myocardial T1 values from normal myocardial T1 values. Native T1 mapping has shown diagnostic promise in amyloidosis , as natiAnderson-Fabry is a disease with accumulation of glycosphingolipids within lysosomes, causing progressive fibrosis in certain tissues . Native Furthermore, differences in myocardial T1 values at RV insertion points between patients with and without pulmonary hypertension (PH) were highlighted by blood correction , suggestThis study included patients with known or suspected heart disease to develop and validate a blood correction method. Patients were used in order to yield the clinical ranges of myocardial and blood T1 values necessary for determining meaningful correlations. As patients were used, this also sometimes resulted in changes in the MOLLI acquisition parameters with varying FoV size and phase encoding lines, which can influence the accuracy of the T1 measurement. However, the strategy used underscores that the resulting blood correction model is valid for clinical use, since adjusting image acquisition parameters is a part of the clinical routine. Furthermore, only septal myocardial T1 values were acquired, and not all segments according to American Heart Association (AHA) segmentation scheme, which has been used in other studies , 48. NotBlood correction improves the precision of native myocardial T1 measurement by 13% and reduces gender differences. Image-based correction of native myocardial T1 values for R1 and R1* of blood is valid for clinical use and may improve disease detection in the clinical evaluation of native myocardial T1, and reduce sample size needs for clinical research.


Parametric mapping promises improvements in patient care through advances in quantitative diagnostics, inter- and intra-patient comparability, and relatedly improvements in treatment. There is a multitude of technical approaches and potential applications. This document provides a summary of the existing evidence for the clinical value of parametric mapping in the heart as of mid 2017, and gives recommendations for practical use in different clinical scenarios for scientists, clinicians, and CMR manufacturers.Parametric mapping techniques provide a non-invasive tool for quantifying tissue alterations in myocardial disease in those eligible for cardiovascular magnetic resonance (CMR). Parametric mapping with CMR now permits the routine spatial visualization and quantification of changes in myocardial composition based on changes in T1, T2, and T2*(star) relaxation times and extracellular volume (ECV). These changes include specific disease pathways related to mainly  Unlike T1-, T2-, or T2*-weighted images, mapping permits both visualization and quantification of the disease process, independent of whether myocardial disease is focal or diffuse. This innovation is important because historically, diffuse myocardial disease related to specific disease pathways has been difficult to non-invasively quantify or even appreciate.CMR is the primary imaging modality for myocardial tissue characterization. CMR parametric mapping now permits the routine spatial visualization of quantitative changes in myocardium based on changes in myocardial parameters T1, T2, T2*(star) and ECV. These changes include specific disease pathways related to mainly Precision Medicine. In addition, CMR parametric mapping also promises to facilitate the development of novel therapeutics, by providing quantitative endpoints reflective of the disease pathway of interest, especially in phase 2 efficacy trials. Technological advances now permit routine acquisition of parametric maps in patients eligible for CMR. While mapping adds unique and relevant diagnostic information on the status of the myocardium, its clinical application requires specific hardware, software, data acquisition and evaluation procedures, which are not completely standardized.Our technical capabilities with parametric mapping may exceed our understanding of how this data can guide optimal treatment for patients with signs or symptoms of underlying disease. Nonetheless, there is an important precedent demonstrating that image guided care exploiting CMR parametric measurements can improve patient outcome in iron overload states . Thus, aThis document provides recommendations for clinical and research applications of CMR myocardial T1, T2, T2*, and ECV mapping. We cite published evidence when available and provide expert consensus where incomplete. We recognize a priori that multiple methodologies for CMR parametric mapping do and should exist, with continued evolution and residual imperfections. Despite these limitations, abundant evidence demonstrates that parametric mapping appears robust under many conditions in its present form. We make analogy to another key cardiac imaging biomarker, the left ventricular ejection fraction (LVEF), where measurement variations persist within and across modalities, yet the yield of biological information is sufficient to diagnose disease, guide and monitor treatment, and to predict outcome. CMR parametric mapping goes beyond nonspecific functional surrogate markers of cardiovascular disease such as LVEF. Rather, CMR parametric mapping offers the potential to examine specific disease pathways that affect myocardial tissue composition.Consensus Group on Cardiac MR Mapping has formed itself to provide guidance on CMR mapping to scientists, clinicians, and manufacturers. The team includes experts with a wide and representative range of technical and clinical expertise, a broad geographical base and a balanced spectrum of interest.In 2013, the “T1 Mapping Development Group” published a consensus statement that proposed suitable terminology and specific recommendations for site preparation, scan types, scan planning and acquisition, quality control, visualization and analysis, and technical directions [Considering the rapidly increasing interest in mapping-based myocardial tissue characterization, the group developed this document to provide 1) an update on the available experimental and clinical evidence, 2) an updated list of clinical indications, 3) practical recommendations for state-of-the-art protocols and techniques, and 4) guidance for research.Table Parametric mapping is useful in patients undergoing evaluation for suspected myocardial disease, and masses.In the clinical scenarios of potential iron overload, amyloidosis, Anderson-Fabry disease, and myocarditis, cardiac mapping provides unique information to guide clinical care and should be applied Tables ; Fig. 1.Parametric mapping should be considered in the diagnostic evaluation of all patients with heart failure and unexplained troponin elevation.The choice of CMR mapping techniques and protocols should be guided by the clinical context.In patients receiving extracellular gadolinium-based contrast agents, routine assessment of ECV may be reasonable.Centers undertaking parametric mapping should fulfill the site requirements described in Rationale and diagnostic potential of parametric mapping techniques.T1, ECV and T2 mapping are typically performed at 1.5 or 3 Tesla (T).T2* mapping for iron overload currently should be performed at 1.5 T.CMR mapping sequences for clinical use should have a published clinical evidence base.Where mapping is clinically reported, the use of a commercial pulse sequence is preferable if supplied by the manufacturer. Other pulse sequences can be considered, but both need to fulfill (1) above.For native T1 and T2 mapping, local results should be benchmarked against published reported ranges, but a local reference range should be primarily used.Reference ranges should be generated from data sets that were acquired, processed, and analyzed in the same way as the intended application, with the upper and lower range of normal defined by the mean plus and minus 2 standard deviations of the normal data, respectively.If local reference ranges are not available for native T1 and T2 mapping, quantitative results should not be reported clinically.For scenarios with large-magnitude biological changes , lower precision is acceptable; e.g. native T1 and T2 reference ranges on the basis of 15 healthy subjects or 20 normal individuals  may be sufficient.For small-magnitude biological changes , high precision is required for native T1 and T2 mapping; e.g. gender +/− age adjusted reference ranges derived from 50+ healthy subjects.For ECV, reference ranges from the literature using the same CMR system and same pulse sequence may be acceptable, as the dependence of ECV on field strength, sequence choice and imaging parameters appears lower than for native T1.For T2*, a 3-tier risk model  for cardiac iron overload should be used if images are acquired at 1.5 T with ≥8-point gradient echo pulse sequences.Tracking changes over time requires the use of identical imaging parameters or high-precision reference ranges (see b).The required precision of the local reference range depends on the proposed clinical application:Once a reference range is established, the major scan parameters , contrast agent/dose and systolic/diastolic phase should not be changed.Regularly repeated phantom-based quality control is recommended to ensure that status and stability of the CMR system have not changed significantly during the time between establishing normative values and clinical scanning.Phantom-based quality control should be performed every time there is a change to the CMR system , a software installation, and every 3 months.Native T1, T2, and T2* are measured in the absence of contrast agents .Motivation and detailed instructions of patients are important to avoid incomplete breath-holds or motion artifacts.In-plane motion correction is recommended if available, but is not a replacement for breath-holding in non-navigated techniques.Volume-selective B0 shimming focused on the heart is highly recommended at 1.5 T, and essential at 3 T. B1 (radiofrequency) volume shimming is recommended at 3 T.In-plane resolution should not be increased to levels where the resulting acquisition duration of the source images exceeds the time frame within the cardiac cycle where data can be acquired without blurring effects by the giving technique, with consideration of the subject’s heart rate.Diastolic image acquisition is recommended if there is a regular heart rhythm.In patients with tachycardia, specific sequences designed for higher heart rates can be useful.In patients with atrial fibrillation, image acquisition should be repeated to allow for averaging of the results. Systolic readout has been shown to produce robust T1 maps in tachyarrhythmias but requires specific normal values.In patients with pacemakers or implanted cardiodefibillators (ICDs), CMR parametric mapping is not reliable unless specific shimming algorithms or sequences can be used to minimize the impact of artifacts.Optimized acquisition schemes for post-contrast acquisitions can be used to gain precision.For Look-Locker-based techniques (e.g. MOLLI), correction for readout-induced deflection of T1 relaxation is required (Look-Locker correction).An extracellular contrast agent with non-protein bound distribution should be used for the assessment of ECV.Gadolinium based contrast doses of 0.1 – 0.2 mmol/kg are recommended.Hematocrit for the calculation of ECV should be obtained immediately before the scan if possible, otherwise within 24 h of scanning.For ECV measurements, post-contrast T1 mapping should be performed 10 – 30 min post contrast administration.Split dose protocols (e.g. in adenosine perfusion scans) can be used to assess ECV. The timing should be taken from the last dose.T2-prepared balanced steady-state free precession (bSSFP) or gradient echo pulse sequences with a minimum of 3 source images are recommended.GraSE or turbo spin echo (TSE) approaches may be appropriate if published data on accuracy and precision are available and favorable.Two-parameter fitting is appropriate.Saturation pulse acquisition may help to remove T1 recovery bias.If available, T2* mapping should be performed at 1.5 T .Multi-echo gradient echo with 8 equally spaced echoes ranging from 2 to 18 ms may be used at 1.5 T.A dark-blood approach is recommended if available.T2* for the assessment of iron overload an interventricular septal region-of-interest (ROI) is recommendedFor the concomitant assessment of liver T2*, the use of fat saturation and the shortest echo time (TE) available are recommended.Added pulse sequences should not compromise the primary study indications.Proper adjustment of main magnetic field shim and center frequency should be assured to minimize off resonance.Through-plane partial volume effects should be minimized where possible by choosing slice orientations that are located orthogonal to the target structures. Caution is required in short axis views of the apex.Image quality should be reviewed during acquisition (e.g. by monitoring sequence sounds and electrocardiographic (ECG) gating), and by looking at source images, error maps, and other quality control maps). Scans should be repeated if sub-optimal or non-diagnostic.Native and post-contrast T1 maps should be acquired using the same slice prescription and other scan parameters at the same cardiac phase .A comprehensive imaging protocol for myocardial tissue characterization including parametric mapping is presented in Fig. a) For global/diffuse disease, a basal and mid short axis map should be acquired with an optional single long axis map.b) For patchy disease, the acquisition of at least one long axis map is mandatory  in addition to basal and mid short axis maps.c) For focal and/or acute disease, additional short axis maps should be added and should cover an area of maximal abnormality and an area of apparently minimal abnormality (as determined on cine and/or T2-weighted images) or the whole left ventricle (if information from cine and T2-weighted images should not be available at the time of image acquisition).d) Whole heart coverage may add diagnostic yield but risks disproportionately long imaging protocols and patient fatigue.Inline ECV maps  can be a useful alternative to manual ECV calculations.Reporting clinicians should learn how to review source images and quality control maps to ensure registration/significant artifacts not present.Maps may be displayed in color if the color look up tables are set according to site-specific ranges of normal, or in gray scale in combination with appropriate image processing, to highlight areas of abnormality.For global assessment and diffuse disease, a single ROI should be drawn in the septum on mid-cavity short-axis maps to avoid lung, liver and veins as sources of susceptibility artifacts.In case of artifacts or non-conclusive results on mid-cavity ROIs, basal ROIs can be used for validation.For focal disease, additional ROIs might be drawn in areas of abnormal appearance on visual inspection. Very small ROIs (<20 pixels) should be avoided.ROIs should be checked if generated automatically.Drawing ROIs on greyscale may avoid bias.Myocardial ROIs should be placed accurately to minimize partial volume effects from adjacent blood pool or extra-myocardial tissues.ROIs should be drawn independently of late gadolinium enhancement (LGE) fibrosis imaging. It is acceptable for ROIs to exclude infarcts  and include non-ischemic LGE.There is currently no specific recommended/preferred analysis software package. The image reader should be trained with the local standards and with the analysis software package of choice and be aware of and familiar with the appearance of artifacts.Sensitivity of mapping techniques to confounders such as heart rate and magnetic field inhomogeneities should be considered during interpretation.For clinical reports, the type of pulse sequence, reference range, and type/dose of gadolinium contrast agent (if applied) should be quoted.Mapping results should include the numerical absolute value, the Z-score , and the normal reference range.An interpretation should be given as normal, mild, moderate, or severe increase/decrease.Best practice is defining the severity of deviation based on prognostic data. If such data are not available (as is the case for most applications of cardiac mapping) and no published suitable scheme is available, the findings may be classified as mild, moderate, and severe, referring to tertiles of the known spectrum of disease severity.Cardiac mapping techniques extend the diagnostic capabilities of CMR by enabling the quantification of CMR signal changes on an absolute scale. Conventional CMR techniques require a reference tissue  to detect alterations of myocardial tissue composition. The direct quantification of myocardial tissue properties effectively eliminates the need for such a reference tissue, which makes parametric mapping the first CMR tool that allows for direct assessment of diffuse myocardial disease.The different cardiac mapping techniques provide specific parameters of the myocardium . While changes of these parameters are not specific for single diseases, they might serve as valuable biomarkers in the context of specific clinical scenarios, as changes of these parameters can be grouped into different patterns depending on the underlying pathology and reflect significant alterations in myocardial tissue composition Fig. , Table 5As with any novel diagnostic approach, much of the research initially published in the field of parametric mapping was centered on advances in acquisition methodology. With a multitude of fast and robust mapping techniques described in the literature, some of which are commercially available on modern CMR systems. There is now growing evidence on the clinical value of CMR myocardial mapping from large-scale clinical outcomes trials. In principle, CMR myocardial mapping techniques hold important potential for making diagnosis, risk-stratifying, and monitoring therapy. Thus, parametric mapping can be regarded as a natural extension of comprehensive CMR protocols for the assessment of myocardial disease.CMR mapping of T1, T2, T2*, and estimation of ECV in the clinical setting has intensively been studied over the past decade. Until very recently, the necessary pulse sequences and post-processing software have not been commercially available. Scientific developments in the field have mainly been driven by single large CMR centers, while evidence from multi-center trials is limited. Thus, current levels of evidence in the field mainly rely on single-center studies and opinions of experts who perform CMR mapping sequences in clinical routine for several years.The present recommendations intend to introduce the concept of development steps towards the clinical application of T1, ECV, T2, and T2* mapping. These steps are defined by the available evidence supporting the clinical use of particular mapping sequences for the assessment of distinct disease patterns.The proposed levels of utility are A) established applicability and usefulness which has been demonstrated by several clinical trials performed by more than one CMR center; B) emerging utility, defined as applications that have been proven useful in only one center; and C) potential applications, i.e. applications that have so far only been tested in experimental settings or animal models.The most common method for measuring relaxation times is to acquire a series of images in which the time to readout after inversion had been varied over a sufficiently wide range. The relaxation time can then be calculated on a pixel-by-pixel basis by fitting the image intensity of the series against the parameter that was used to vary the relaxation time weight. This pixel-wise relaxation time fitting needs to meet two conditions in order to be accurate and to avoid bias: 1) the variation in weight of other factors  is negligible or corrected for, and 2) there is negligible physical displacement between the images in the series. In the case of CMR, cardiac and respiratory motion make meeting both conditions more challenging: avoiding motion artifacts limits the pulse sequence choices. Cardiac motion is normally avoided by only acquiring for a sufficiently short duration at mid-systole or end-diastole, while respiratory motion can be avoided or compensated for through breath holding or navigator gating, respectively. Any residual image-to-image displacement  can potentially be corrected through affine or non-rigid image registration after the acquisition and before pixel-by-pixel fitting. After the maps have been generated, several segmentation options are available: 1) the entire LV myocardium is segmented to establish an average value or perform a threshold-based analysis to determine areas of abnormality as a percentage of the LV myocardium, 2) the septal region is segmented, 3) the myocardium is divided into 16 segments as defined by the American Heart Association guidelines, or 4) ROIs are drawn in regions of pathology and healthy (remote) tissue for comparison. Option 2  is mandatory for T2* mapping due to frequent artifacts in other regions of the myocardium , and might also be preferable for the assessment of diffuse myocardial disease by T1 and T2 mapping because of a high level of robustness and ease of omitting contamination from epicardial fat.1 have been described. The majority of sequences utilize multiple single-shot bSSFP acquisitions, using inversion preparation , saturaion  or a coSAPPHIRE ).1 mapping [2, flip angle, inversion pulse efficiency, heart rate and off-resonance, which reduces its accuracy [The modified Look-Locker  inversio mapping , 5, 14.  mapping , T2, fliaccuracy –18. Variaccuracy . The MOLaccuracy  and the accuracy , with liaccuracy , 19–22.. SAturation Pulse Prepared Heart-rate-independent Inversion REcovery (SAPPHIRE) uses a hybrid of saturation and inversion pulses to improve precision of the saturation-recovery approach while maintaining accuracy [Saturation-based approaches typically use a single image acquisition per preparation pulse, minimizing the complex magnetization history of the Look-Locker approaches, and largely eliminating sensitivity to MT, T2, heart rate and off-resonance effects at the price of reduced precision , 15, 16.accuracy .Researchers continue to address the challenges of optimizing accuracy and precision with new acquisition and processing methods, for example, with the use of Bloch equation-based T1 corrections for MOLLI acquisitions –25 and aT1 mapping can be used to estimate the myocardial ECV, a validated surrogate marker of fibrosis –31 in thFor T1 mapping acquisition methods, T1 values are estimated by fitting a T1 recovery curve to each pixel in a series of images with different degrees of T1 recovery using a two- or three-parameter fit . TherefoIn the presence of edema, myocardial T2 will increase. T2 weighted CMR imaging is commonly used to assess myocardial inflammation. However, image quality, reproducibility and subjective assessment of T2 weighted images have been limiting factors in its clinical adoption. To overcome these challenges, regional myocardial T2 mapping has emerged to directly quantify local myocardial inflammation and edema. Few studies have investigated the value of T2 mapping in other myocardial diseases . T2 mappT2* relaxation mapping is usually based on GRE sequences and forms the basis for numerous CMR applications . In partThe analysis is restricted to the septum to reduce susceptibility artifacts. A multi-slice T2* approach has also been proposed, which may have advantages for the evaluation of myocardial hemorrhage in acute myocardial infarction by providing whole-heart coverage. The single-slice technique based on the septal analysis remains accepted practice [For the measurement of myocardial T2* in vivo, a mid-ventricular short axis slice is acquired and a homogeneous ROI is defined encompassing both sub-epicardial and sub-endocardial regions, as iron is preferentially stored in the sub-epicardial compared with the sub- endocardial layers . The anapractice .2 or error), if available, and the parametric maps to assess for quality, reacquiring images as necessary. For instance, motion may manifest as obvious diaphragmatic motion or variation in cardiac phases on the raw images, areas of poor curve fit on quality control maps, or blurring of tissue borders on T1/T2 maps. For T2* measurements, poor breath holding and cardiac motion typically manifests as ghosting, and may significantly affect image and data quality. Off-resonance artifacts may be particularly prominent at 3 T, and the use of a local box shim is essential to reduce off-resonance variation across the heart.Changes in CMR system hardware and software may lead to changes in mapping sequence parameters . During image acquisition, mis-triggered heart beats, motion (cardiac and respiratory), and off-resonance or other artifacts may lead to inaccurate measured relaxation times  do not exhibit the exact same normativevalues as human hearts.Reporting). This situation actually resembles that of other biomarkers including serologic tests, where reference values of the local laboratory are usually provided along with the results sheet. In the future, it might become possible to normalize native parameter results to a “standard parameter” based on phantom or software calibration methods [As a consequence, native parameter values should only be compared to other parameter values if they are obtained under similar conditions. In other words, the acquisition scheme, field strength and processing approach should be the same, and the results should be reported along with corresponding reference ranges for the given methodology  that arT1, T2, and T2* times of a given pixel in a respective parametric map represent a composite signal of the corresponding tissue voxel. Changes of myocardial tissue composition lead to alterations of T1, T2, and T2* times. Such changes usually occur in the same direction (i.e. shorten or lengthen) for all three magnetic properties but might not reach the same degree in all of them, depending on the underlying process. ECV behaves different in that it only reflects alterations of the extracellular component of the myocardium. Table 10 gives an overview on principal directions and degrees of changes in parameters depending on pathology.As acute myocardial edema develops in areas of acute ischemia and infarction, native T1 and T2 relaxation times prolong, whereas post-contrast T1 time shortens, compared to remote myocardium , 73, 74.Increases in myocardial free water content, as occurs in acute myocardial edema and inflammation, prolong T1 and T2 relaxation times , 86; wheWhile the key measure determining the need for valve replacement in aortic stenosis is the degree of valvular obstruction, the myocardium also undergoes progressive changes that can lead to deteriorating cardiac performance and increased morbidity and mortality . The degSimilar to the response to pressure overload in aortic stenosis, CMR T1 mapping studies in patients with arterial hypertension have demonstrated small degrees of expansion in ECV that parallels the development of LV hypertrophy . FurtherTwo types of amyloidosis commonly infiltrate myocardium: immunoglobulin light-chain derived (AL) and transthyretin (ATTR) amyloid. While these two types have different natural history and prognosis, cardiac involvement drives outcome and therapeutic choices in both. Early recognition and therapy are critical in AL amyloidosis when cardiac involvement is detected. CMR with LGE has been shown to be a valuable tool in cases with typical subendocardial tramline pattern, which is replaced by transmural RV and LV enhancement at later stages. However, atypical patterns have been described and renal impairment restricting contrast use is common in amyloid. Native T1 mapping may allow for making the diagnosis of cardiac amyloidosis without the need for gadolinium contrast application, although the normal T1 in renal disease is not yet well defined –112. ECVIron overload), in around 85% of all subjects with LV hypertrophy, though to be directly related to sphingolipid storage [Anderson-Fabry disease is a rare X-linked lysosomal storage disease that causes LV hypertrophy and eventually fibrosis and heart failure. The underlying pathology is intra-cellular accumulation of glycosphingolipid. Native T1 in this disease is low, unlike any other cause of hypertrophy except for iron overload  or increased intestinal iron absorption (e.g. hereditary hemochromatosis). Iron overload leads to severe heart failure and lethal arrhythmias but can be treated effectively if diagnosed early. T2* mapping is an accurate and reliable method for the quantification of cardiac iron load . It is rRecently, T1 mapping has also been evaluated for the assessment of cardiac siderosis, and compared with T2 and T2* in a substantial population with and without cardiac iron overload , showingECV may be increased in patients with thalassemia major and is associated with cardiac iron overload . Howeverquantifies the interstitial presence of gadolinium relative to the plasma. Accordingly, histologic validation data overall show best agreement with ECV compared to other T1 metrics based on R2 values  [Myocardial fibrosis occurs in a continuum from mild to severe where excess collagen (concentration) appears in the myocardial interstitium . Accordiariable) , 132. Deariable) , 133–138ariable) , 140), sariable) ; thus LGpositive correlation between myocardial fibrosis (whether by ECV or histology) and LV mass suggests significant primary fibroblast activation since myocyte loss would decrease LV mass [ECV dichotomizes the myocardium into its primarily cellular compartment and predominantly interstitial compartment  . While m LV mass . This inEmerging data reveal that many cardiac insults culminate in myocardial fibrosis, and the extent of fibrosis can vary across disease categories . The extDilated cardiomyopathy and hypertrophic cardiomyopathy are associated with the development of diffuse myocardial fibrosis. In both groups of patients, native T1 was found to be increased not only in areas corresponding to LGE but also in areas without LGE, hence suggesting that native T1 can detect areas of tissue pathology beyond those detected by LGE . In patiFibrotic remodeling as a consequence of chronically increased afterload has long been recognized. Even young patients with aortic stenosis exhibit increased ECV, which correlates with the degree of diastolic dysfunction . In addiAcute ischemic injury), myocardial infarction also causes changes of native T1 in the chronic stages of the disease. However, the heterogeneous nature of these changes both within and in between subjects limit the sensitivity of native T1 for the detection and – even more so – the quantification of the extent of chronic myocardial infarction in a given individual [Acute ischemic injury), and was associated with LV remodeling and adverse cardiac events [Besides the severe alterations of native T1 seen in the acute stage  are at particular risk for developing ventricular dysfunction, especially when the dominant ventricle is of RV morphology, as in hypoplastic left heart syndrome . Even atDrug trials for the treatment of heart failure in congenital heart disease have been nearly unequivocally disappointing. Information on myocardial health from T1 mapping might potentially allow for a more personalized pharmacological approach. As pharmacologic heart failure therapies have been less effective in these situations than in acquired heart disease, interventional and surgical approaches play a major role. T1 and ECV mapping have been proposed as tools to guide decision-making and timing of such procedures in the course of the disease. For example, the goal of pulmonary valve replacement in post-repair patients with Tetralogy of Fallot may become preservation of myocardial health over and above restoring RV volume, which is currently at the center of timing for pulmonary valve replacement. Thus, longitudinal RV ECV assessments may prove helpful in making the decision when to restore pulmonary valve competency. However, RV disease is hard to assess with common breath-hold T1 mapping approaches as their spatial resolution approaches the low thickness of the RV wall. Even in patients with right ventricles that support the systemic circulation, the RV free wall has been deemed not measurable by T1 mapping . This prInformation on the prognostic significance of parametric mapping in pediatric cardiomyopathies and myocarditis is scarce, and it remains unclear whether the experience in adults can be extrapolated to children. In patients with chronic Kawasaki disease, ECV is elevated, including in LGE-negative myocardial segments. It is highest in segments supplied by severely aneurysmal and/or obstructed coronary arteries and is associated with decreased myocardial blood flow and strain. Therefore, CMR T1 mapping may present an opportunity to improve risk stratification and monitoring in Kawasaki disease beyond coronary artery angiography and stress testing. In boys with Duchenne muscular dystrophy, heart failure treatment is typically started or intensified when myocardial dysfunction and/or LGE develop. However, even patients with normal LV ejection fraction and no LGE have elevated ECV and T1 values . This obMapping techniques may be used for characterizing extra-myocardial tissues, such as masses, pericardial effusion and fat, although current clinical evidence is sparse for these applications. For instance, cardiac masses with high fat content, such as lipomatous hypertrophy of the inter-atrial septum, may be readily apparent on T1 maps , demonstThe measurement of T1, T2, and T2* relaxation time constants assumes a mono-exponential behavior on a macroscopic scale. This simplifying assumption has proven to be useful in clinical practice for differentiation of tissues and assessment of their state. However, the molecular composition of biological tissue is frequently more complex, leading to multiple compartments with chemical exchange (magnetization transfer) and finite diffusion distances. How the simplified model is affected by more complex molecular composition of tissue and pathology is unclear, and the clinical consequences of the simplified view needs to be studied for various scenarios.The measurement of a parameter of interest such as T1 may depend on other variables such as T2 or patient’s heart rate (HR), and numerous other confounding factors. From a clinical perspective, the consequences of such bias are not fully understood. There are instances for which the confounding factor may make a disease more detectable. However, the interpretation of the shift from baseline normal is no longer clear. For example, an elevated T1 might be due to fibrosis, or might be due to confounding effect of elevated T2 arising from edema. In another example, a decrease in T1 might be due to increased iron concentration, or might be due to off-resonance in the scanner center frequency. Some of the confounding variables are due to patient physiology, but others may be due to scanner adjustments or field inhomogeneities. The extent to which the desired measurement is confounded will depend on both the sequence design and specific protocol. Some of the confounding effects may be disentangled by multi-parametric measurements, or by calibrations scans, but these come at the expense of time and complexity.Partial volume effects arise from a) the contamination of the desired signal by adjacent tissue such as blood pool or fat, or b) mixtures of tissue within the voxel of interest such as intramyocardial fat. Use of blood or fat suppression may help mitigate partial volume effects but may also affect the measurement of interest. The degree to which partial volume errors influence the measurement depends on aspects such as wall thickness or angulation of the slice prescription.Myocardial tissue may be heterogeneous with variation on the scale of the voxel resolution. In this instance, the quantitative measurements are smoothed and represent an average, which may not accurately reflect the focal elevation or baseline normal values. For example, the focal elevation of T1 or T2 may depend on the slice thickness when the focal abnormality is thinner than the slice. This is compounded when ROIs are drawn which introduced further averaging. Thus the degree of heterogeneity and size of focal abnormalities is a factor influencing the quantitative measurement and depends on resolution and manner of measurement and reporting. For example, in assessment of iron overload, where the concentration of iron is heterogeneous, it is unknown whether there is clinical significance of the peak concentration and distribution in addition to the average value quantified in typical analysis. The influence of these effects on clinical assessment needs to be characterized.The impact of the post-processing methodology (i.e. derivation of relaxation times from a set of source images) on the quality of parametric results can equal or sometimes even exceed that of the acquisition strategy. Consequently, advanced post-processing strategies have been investigated. For T1 mapping, several methods have been proposed that aim to optimize T1 estimation from MOLLI source images , 25. In While the assessment of average parameter values of septal ROIs is regarded as appropriate for diffuse myocardial disease, conditions with patchy presentation such as myocarditis  might require more detailed analysis of regional behavior. Histogram analysis  and statFuture developments in cardiac mapping will likely focus on standardization of data acquisition and post-processing, as well as on optimizing workflows. In parallel, the clinical utility of mapping will have to be carefully explored for various cardiovascular diseases to further define where mapping parameters can firmly establish diagnosis, guide therapeutic decisions, and predict prognosis. The robustness of mapping protocols and results will play an important role in its acceptance for clinical decision-making. Challenges include proprietary approaches of CMR system manufacturers, cost for software packages and the need for calibration of hardware and sequence settings.On the technical side, accelerated image acquisition such as compressed-sensing techniques , 186 mayThe combination of mapping with quantitative data from functional (cine) studies can be sufficient to differentiate diseases from physiologic adaptation of cardiac mass, shape and function such as in athlete’s heart , 188.As native T1 and T2 are sensitive to increased myocardial water content and myocardial blood volume, there is current interest to investigate the ability of vasodilatory stress T1 and T2 mapping to detect ischemia without the need for exogenous contrast agents as a novel application of mapping techniques , 140.Several techniques have also appeared that map multiple relaxation times simultaneously (MR fingerprinting) –191, witNon-contrast protocols will be useful for patients with a need for repeated CMR or with kidney failure.Eventually, data on accuracy and prognosis will have to be followed by trials on the impact on patient outcomes. It is likely that relaxation times and ECV may achieve the status of biomarkers Fig. , which aCMR mapping of T1, T2, T2* and ECV provides quantitative information on changes of magnetic tissue properties, which reflect alterations of myocardial tissue composition. CMR mapping methodology has left behind the early stages of principal implementation and validation, and robust techniques are available for commercial CMR systems. Iron overload, amyloidosis, Anderson-Fabry, and myocarditis are clinical scenarios where cardiac mapping provides unique information and should be applied to guide clinical care. Due to its additional diagnostic and prognostic value in the assessment of diffuse myocardial disease, parametric mapping should be considered in the diagnostic evaluation of all patients with heart failure.T1 mapping/ ECV) and that ECV should be given as a percentage (see Terminology).This document provides recommendations related to both clinical indications and practical implementation, and summarizes the underlying rationale. Building on the 2013 Consensus statement on myocardial T1 mapping and extracellular volume quantification [CMR parametric mapping has seen many innovations over the last decade and continuous to attract interest from both basic and clinical researchers. Thus, any consensus document can only attempt to reflect the state of evidence at a single point in time, and will invariably start to be incomplete by the time of publication. Nevertheless, this document is meant to give guidance for CMR clinicians who would like to provide state-of-the-art tissue characterization for patients with myocardial disease.


A 29-year-old woman was referred to our hospital due to exacerbation in dyspnea on exertion and easy fatigability. A known case of congenitally corrected transposition of the great vessels and congenital complete heart block, she had already received a permanent single-chamber pacemaker. Decision was made to implant a biventricular pacemaker for the treatment of the failing heart. Excellent coronary sinus lead implantation was done, conferring amelioration of symptoms, QRS narrowing in the electrocardiogram, and improvement of systemic ventricular systolic function in echocardiography. Over a 15-month follow-up period, she had no dyspnea on exertion. This case highlights the significance of upgrading pacemakers in patients with heart failure. Patients with a systemic right ventricle or single ventricle gradually develop symptomatic systolic dysfunction. Cardiac resynchronization therapy (CRT) is one of the best approaches to treating systemic ventricular systolic dysfunction and ipsilateral bundle branch block (native or pacemaker induced) in pediatric and adult patients.Given the technical challenges in the implantation of CRT devices, we decided to present this case and discuss the pitfalls.We describe a 29-year-old woman, who was referred to our center for the treatment of gradual exacerbation in dyspnea on exertion and easy fatigability of 6 months' duration. A known case of congenitally corrected transposition of the great vessels (CC-TGV), the patient had undergone single-chamber permanent pacemaker implantation via the right subclavian vein owing to complete heart block 14 years previously. Four years later, there was a rise in the capturing threshold of the right ventricular lead, prompting the treating physicians to implant a new lead .3On her referral to our center, she underwent echocardiography, which showed moderate to severe systolic dysfunction of the morphological (systemic) right ventricle. Considering the persistence of the symptoms despite medical therapy, decision was made to implant a CRT device in accordance with the new American College of Cardiology/ American Heart Association 2012 guideline, stipulating that patients with severe systemic ventricular systolic dysfunction and ventricular pacing > 40% of the times be upgraded to CRT.The well-documented challenges of the implantation of a CRT device from the right side  led to the decision to abandon the old leads and implant a completely new system from the left side. ®) into the right anterior oblique (RAO) 30˚ view proved easy. Pacing the lead confirmed a good ventricular capture (capturing threshold = 0.75 × 0.5 Volt msec). The implantation of the coronary sinus lead was done using a peel-away long sheath while injecting through mandarin in the left anterior oblique (LAO) 30˚ projection. A suitable posterolateral branch was visualized. A 4-French dual cathodic Medtronic lead (Attain Ability®) was employed in order to advance the lead as far as possible, minimize the chance of the phrenic nerve stimulation, and maximize interventricular resynchronization (capturing threshold = 1 × 0.5 Volt msec). The coronary sinus lead having been secured, the right atrial lead  implantation was done in RAO and LAO projections during pacing to find the best atrial capturing threshold (capturing threshold = 1 × 0.5 Volt msec)  view failed, but advancing the right ventricular lead (Medtronic CapSureFixlt msec) . After tImmediately after CRT device implantation, electrical resynchronization, manifested as a QRS duration of 80 msec, was achieved . One mon4 implanted a CRT device in a 22-year-old patient with CC-TGV, pulmonary atresia, and ventricular septal defect and reported improved systemic ventricular contractility and systolic blood pressure. Kakavand et al.5 (2006) implanted a CRT device for a 32-year-old patient with CC-TGV, ventricular septal defect, and acute heart failure and reported the immediate hemodynamic effects and improvement of symptoms. The largest retrospective study on CRT device implantation (in 11 CC-TGV patients among 60 patients with CHD) was published by Cechin et al.6 (2009), who reported a decrease in the median QRS width from 149 msec to 120 msec and an increase in the median ejection fraction from 36% to 42% . In that study, 8 out of 13 patients with a single-ventricle morphology had a “strong CRT response”, defined as either an improvement of symptoms and/or increased ventricular function by ≥ 10 ejection fraction units.Rodriguoz-Cruz et al.7 (2009), who performed autopsy in 51 hearts with CC-TGV and found that 10 patients had an abnormal coronary sinus ostium. However, the most important distinction was that the ventricular veins were similar to the smaller epicardial veins that drain the right ventricle in patients without CHD.Regarding the coronary sinus anatomy in patients with CC-TGV, the most comprehensive study was conducted by Bottega et al.Our patient had complete heart block and CC-TGV. As she grew up, her systemic right ventricle gradually failed against the aortic pressure and brought about heart failure symptoms. Despite the small size of her coronary sinus and its branches, the techniques mentioned above enabled us to implant a small coronary sinus lead.We believe that appropriate patient selection, awareness of the technical challenges, and knowledge of the means and ways to overcome them are the three prerequisites for success in implanting CRT devices in CHD patients.Coronary computed tomographic (CT) angiography for the evaluation of the coronary sinus vein and its tributaries prior to CRT device implantation in CHD patients reduces the procedure time. What is more, CT angiography can diagnose abnormalities that may complicate the procedure (e.g. persistent left superior vena cava). Furthermore, different fluoroscopic projections other than the AP view  can help find the retrosternal chamber more easily . The use of contrast rather than deflectable electrophysiology catheters is recommended for the cannulation of the coronary sinus ostium. The availability of multiple coronary sinus leads  enables the operator to advance the lead as for as possible and, thus, maximize resynchronization and minimize the chance of the phrenic nerve stimulation.


There is today no established approach to estimate right ventricular ejection fraction (RVEF) using 2D transthoracic echocardiography (TTE). The aim of this study was to evaluate a new method for RVEF calculations using 2D TTE and compare the results with cardiac magnetic resonance (CMR) imaging and tricuspid annular plane systolic excursion (TAPSE).TTE, were compared with reference CMR-derived RVEF, RVEFCMR. Further, TAPSE was measured in the TTE images and the correlations were calculated between RVEFTTE, TAPSE and RVEFCMR.A total of 37 subjects, 25 retrospectively included patients and twelve healthy volunteers, were included to give a wide range of RVEF. The right ventricle (RV) was modeled as a part of an ellipsoid enabling calculation of the RV volume by combining three distance measurements. RVEF calculated according to the model, RVEFCMR = 43 ± 12% (range 20–66%) and RVEFTTE = 50 ± 9% (range 34–65%). There was a high correlation  between RVEFTTE and RVEFCMR. Bland-Altman analysis showed a mean difference between RVEFCMR and RVEFTTE of 6 percentage points (ppt) with limits of agreement from −11 to 23 ppt. The mean value for TAPSE was 19 ± 5 mm and the correlation between TAPSE and RVEFCMR was moderate . The correlation between RVEFTTE and RVEFCMR was significantly higher (p < 0.05) than the correlation between TAPSE and RVEFCMR.The mean values were RVEFThe ellipsoid model shows promise for RVEF calculations using 2D TTE for a wide range of RVEF, providing RVEF estimates that were significantly better correlated to RVEF obtained from CMR compared to TAPSE.The online version of this article (doi:10.1186/s12947-017-0096-5) contains supplementary material, which is available to authorized users. Right ventricular (RV) function is an important predictor of survival in cardiopulmonary disease . EvaluatThe complex shape of the RV, and the relatively large element of trabeculations, makes its function more challenging to assess as compared to the left ventricle (LV), when using echocardiography. Cardiac magnetic resonance (CMR) imaging is considered to be the reference method for RV evaluation allowing full ventricular coverage. In CMR, right ventricular ejection fraction (RVEF) is often used as a measure of RV function. RVEF can be determined by calculating the end-diastolic and end-systolic volumes of the RV in the short-axis (SA) plane . PreviouThe most common method for RV assessment is, however, transthoracic echocardiography (TTE) due to its high availability compared to CMR. A challenge when using TTE for RV evaluation is the position of the RV behind the sternum . When imEvaluation of the RV using TTE is often made by the one-dimensional measure of TAPSE along with quantification of the RV size, often by measuring the RV diameter, and a visual evaluation of the concentric movement of the RV free wall. The fact that TTE provides a real time image of the ventricle function is an advantage, but the visual assessment might imply risk of subjectivity. Also, when using TAPSE the objective evaluation of the RV is only one-dimensional with a focus on longitudinal movement of the free wall and potential information may be left out in terms of global function. The inclusion of more than one distance measurement in the evaluation of the RVEF using TTE is a conceivable alternative for achieving a more consistent measure of RVEF which relies on a three-dimensional property (volume).In a previous study, on healthy individuals, we have presented and evaluated a model for RV volume estimations , where tTTE) and reference CMR-derived RVEF (RVEFCMR) and ii) comparing the correlation for RVEFTTE and TAPSE to RVEFCMR for a group of subjects with a wide range of RVEF.The aim of the present study was to evaluate whether the ellipsoid model can be an alternative to TAPSE for RVEF estimations by i) estimating the agreement between RVEF obtained by the ellipsoid model  between the ellipsoid model and the reference, with an estimated standard deviation (SD) of 10, power 80% and α = 0.05. The power analysis concluded a minimum of 34 subjects.Twenty-five patients with reduced RV function, and examined with both TTE and CMR, were retrospectively included in the study. Patients were identified in the radiology information system (RIS) using a list of all CMR examinations performed between January 2012 and May 2015. A subject was included if there was an entry of a reduced RV function in the clinical CMR report and a TTE examination had been performed within three months from the CMR examination. All subjects younger than 18 years were excluded. The criteria for inclusion in the study was met if there was a notification of reduced RV function in the CMR report defined as RVEF <50%, TAPSE <20 mm or based on visual assessment. The exact degree of reduced RV function for a specific patient was not crucial, since to the aim was to get a variety RVEF. Care was taken to ensure that the patients had not undergone any cardiac intervention of significance during the time between CMR and TTE, such as surgery and treatments including electrophysiology or potent drugs, which could have influenced on cardiac function. In this regard, care was also taken to ensure that the loading and filling conditions did not differ significantly between the two examinations such as heart rate, presence of severe valve dysfunctions and/or pericardial effusion.In addition to the 25 patients, the twelve healthy volunteers from the previous ellipsoid study  were incThe Regional Ethical Review Board approved the study and waived the informed consent requirement for the retrospectively included patients, while written informed consent was obtained from the healthy subjects.The healthy subjects were examined by TTE and CMR at the same day and location, separated by less than 30 min.All CMR examinations were performed on a clinical 1.5 T Philips Achieva system . A retrospectively triggered balanced turbo field echo (b-TFE) pulse sequence was used for the acquisition of conventional images. The following parameters were applied; TR/TE shortest , pixel size typically 1.5x1.5 mm2, flip angle 60°, 1 NSA. For the retrospectively included patients an acceleration factor (SENSE) of 2 was used, while no acceleration factor was used for the healthy subjects (SENSE = 1). For the retrospectively included patients the slice thickness/slice spacing was 5/8 mm and 30 consecutive heart phases were used for the SA images for all patients but one where 13 consecutive heart phases were used for the SA images. For the healthy subjects the slice thickness/slice spacing was 8/8 mm and 20 consecutive heart phases were used for the SA images. The protocol applied for examination of patients was slightly different from the protocol used for the healthy volunteers. The main reason for this difference is the adaptation of the protocol to a lower breath hold ability of the patients compared to healthy volunteers.The TTE examinations of the group of patients were performed using three different types of commercial ultrasound scanners: General Electric Vivid E9 , Siemens ACUSON SC2000  or Philips iE33 . Each system was equipped with a compatible transducer (phased array and multi-frequency based). The examinations had been carried out as in clinical routine, with the subjects in the left lateral recumbent position and ECG-triggering, thus, including digital storage of moving clips (i.e. cine-loops) from standardized views, allowing offline measurements. The TTE examinations of the healthy group were performed solely using one kind of ultrasound system (GE Vivid E9). As in clinical routine, these examinations also included standardized collection procedure and digital storage of cine-loops (from standardized views).3), right ventricular long axis (RVLAX) and the left ventricular maximum outer basal diameter (LVD). The right ventricular volume (RVV) is then approximated as:The RV was approximated by an ellipsoid as previously described . In shorFor a detailed derivation of the equation see 3, RVLAX and LVD, were measured in diastole and systole in the stored TTE images (i.e. 2D cine-loops). RVIT3 and RVLAX were measured in apical 4CH view, while LVD was measured in apical two-chamber (2CH) view .Offline analysis, regarding all of the TTE examinations, was done using dedicated software . All TTE measurements were calculated as the average of up to three different cardiac cycles, as in clinical routine, with regard to image quality and the amount of images per view.http://www.segment.heiberg.se/ [In SA CMR images the end-diastolic and end-systolic volumes were achieved by manually delineating the endocardium of the right ventricle using the freely available software Segment version 2.0 R4800 , and one master of science in biomedical engineering with 3 years’ of experience in the scientific TTE field but limited clinical experience (observer 2). The CMR measurements were performed by one radiologist with 4 years of experience (observer3), and one master of science in biomedical engineering with 5 years’ experience in the scientific CMR field but limited clinical experience (observer 2).Inter-observer  agreement for each modality was performed.TTE and RVEFCMR. These mean values were used for the inter-modality agreement evaluation.The mean value for the two observers for each method was calculated to give RVEFr < 0.3), low (0.3 < r < 0.5), moderate (0.5 < r < 0.7), high (0.7 < r < 0.9) and very high (r > 0.9) [p < 0.05 was considered to indicate statistical significance.Shapiro-Wilk’s test was used to determine normality of the data. Paired Student’s t-test was used to test the significance for normally distributed differences, while Wilcoxon signed-rank test was used for non-normally distributed differences. Bland-Altman limits of agreement method were used to evaluate the differences  for bothr > 0.9) . Steigerr > 0.9) . StatistThe 25 retrospectively included patients had a mean age of 55 years , while the twelve healthy subjects had a mean age of 36 years . The TTE and CMR examinations for the 25 patients were separated by a maximum of 77 days  (Table r = 0.80 (p < 0.001) between RVEFTTE and RVEFCMR, while the correlation between TAPSE and RVEFCMR was moderate r = 0.54 (p < 0.001) . RVEFTTE obtained from the ellipsoid model was 50 ± 9% (range 34–65) and RVEFCMR was 43 ± 12% (range 20–66). There was a significant difference between RVEFTTE and RVEFCMR using Wilcoxon signed rank test . The mean value for TAPSE was 19 ± 5 mm. Figure TTE and RVEFCMR. The standard deviation for the differences of the mean values in the Bland-Altman analysis was calculated according to the recommendation for analyzes based on mean values [There was a high correlation 01) Fig. . The cor9% range 4–65 and n values .Fig. 2CoTTE and RVEFCMR for the remaining subgroup of 25 patients was moderate, r = 0.62 (p < 0.01), while the correlation between TAPSE and RVEFCMR was low, r = 0.34, and could not be statistically verified. There was a significant difference (p < 0.001) between RVEFTTE and RVEFCMR for this subgroup of 8 ± 8 ppt (95% CI: 4.1-11).When the healthy subjects were excluded, the correlation between RVEFTTE obs1 = 47 ± 10 (range 30–65), RVEFTTE obs2 = 52 ± 9 (range 34–70), RVEFCMR obs2 = 42 ± 14 (range 17–68) and RVEFCMR obs3 = 45 ± 12 (range 18–63). An additional file contains the RVEF values for each subject . This inter-observer agreement can also be considered as an intra-modality agreement since they rely on data from the same modality. The correlation between RVEFTTE obs1 and RVEFTTE obs2 was high r = 0.73 (p < 0.001), while the correlation between RVEFCMR obs2 and RVEFCMR obs3 was very high r = 0.91 (p < 0.001).The results for the RVEF calculations of each observer were RVEFCMR was significantly lower compared to the high correlation between RVEFCMR and the RVEF obtained using the ellipsoid model. This difference in correlation might seem reasonable since the ellipsoid model combines distances expanding a volume while TAPSE provides a one-directional estimate.Determination of RVEF is an important parameter in the assessment of cardiovascular diseases. There is today no established method for measurement of RVEF based on volume estimations using 2D TTE. The results in this study show that a combination of three conventional distance measurements in 2D TTE provides volume-based estimations of RVEF that strongly correlates to CMR for a clinically relevant range of RVEFs. The distances can easily be measured in the 2D TTE images and is not dependent on a complete visualization of the RV free wall which remains as a challenge in echocardiography. The time for measuring the distances necessary for the ellipsoid model is, after some initial testing at our department, considerably shorter compared to RVEF calculations using 3D TTE data with post processing software. The ellipsoid model is not necessarily less time-consuming compared to other conventional 2D parameters ), although it may be recognized with relatively high applicability in this regard; since it does not require full visualization of the entire RV free wall. The moderate correlation between TAPSE and RVEFAn upcoming method for RV evaluation is longitudinal STE strain for regional or global analysis of the RV free wall. STE strain enables quantification of the RV free wall which, compared to Doppler tissue imaging strain, is less angle dependent but the need for good image quality and full visualization of the RV free wall is still present . A recenThere was a small but significant mean difference regarding RVEF as estimated with the ellipsoid model compared to CMR, where the ellipsoid overestimates the RVEF. As seen in Figs. The correlation between RVEF estimated by the ellipsoid model and CMR was lower for the subgroup of 25 patients compared to the correlation for all subjects, but still at a moderate level, while there was no correlation between TAPSE and CMR for this subgroup. This indicates that the ellipsoid model provides a better estimate of global RV function compared to TAPSE. The fact that there were up to three months between the TTE and CMR examinations for the patient group is a possible reason for the greater differences and lower correlation, along with the issue of abnormal RV morphology discussed above. Also, the number of subjects and the distribution of the RVEF-values differ when comparing the correlation coefficient for the subgroup of 25 patients to the correlation coefficient for all 37 subjects. A prospective study, performing CMR and TTE examinations on the same day for a group of subjects with a wide range of RVEF values, is needed to further evaluate the ellipsoid model.In TTE, according to our experience, RVEF is quite often determined by visual estimation of the concentric movement of the RV free wall, along with TAPSE measurements. We believe that this new method for RVEF calculations is a way to improve the RVEF estimations using TTE, and making it less subjective.Looking at the intra-modality agreement there was a high correlation for TTE compared to a very high for CMR. There was a slightly smaller bias and more narrow limits of agreements for CMR compared to TTE. This indication, that CMR measurements are more reproducible, agrees with CMR being considered to be the reference for such measurements. Also, the inter-observer variability may be affected by the difference in clinical experience between the observers.CMR and TTE complement each other and a multi-modality approach is often a good alternative when possible. We believe, however, that this new method proposed for RVEF calculations using TTE may be of value when CMR is not possible.One of the dimensions in the ellipsoid model is based on a left ventricular measure (LVD) and is not a direct right ventricular measure. This could influence the accuracy for groups of patients, such as patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), due to the risk of an increase of the right ventricle width in this direction, which not necessarily leads to an increase of the left ventricular diameter. Further evaluation of the model’s applicability for this group of patients is necessary. An alternative to using the LVD measure in the equation, could be to replace it with the corresponding measure of the RV in a basal parasternal short-axis view, possibly resulting in better agreement also for patients with abnormal RV morphology.3, the apical 4CH view should be focused on the RV, as recommended in the guidelines [When measuring RVITidelines . For theThe fact that it was up to three months between the examinations for the retrospectively included patients might influence the results.In this study, CMR is used as reference method. It is the method commonly used as reference method for ventricular volume calculations, but it is however important to remember that the calculations by CMR also are estimations. In particular for the RV, delineation of the endocardium is a difficult task and the true value remains unknown.The ellipsoid model provides an alternative for RVEF calculations using 2D TTE that gives a higher correlation to CMR compared to TAPSE for a wide range of RVEF. An incomplete visualization of the RV free wall, which is a common challenge in TTE, is not a restriction for the application of the method.


Idiopathic inflammatory myopathy (IIM) is a group of autoimmune diseases with systemic myositis which may involve the myocardium. Cardiac involvement in IIM, although often subclinical, may mimic clinical manifestations of acute viral myocarditis (AVM). Our aim was to investigate the usefulness of the combined analysis of cardiovascular magnetic resonance (CMR) T1 and T2 mapping parameters measured both in the myocardium and in the thoracic skeletal muscles to differentiate AVM from IIM cardiac involvement.Sixty subjects were included in this retrospective study : twenty patients with AVM, twenty patients with IIM and cardiac involvement and twenty healthy controls. Study participants underwent CMR imaging with modified Look-Locker inversion-recovery (MOLLI) T1 mapping and 3-point balanced steady-state-free precession T2 mapping. Relaxation times were quantified after endocardial and epicardial delineation on basal and medial short-axis slices, as well as in different thoracic skeletal muscle groups present in the CMR field-of-view. ROC-Analysis was performed to assess the ability of mapping indices to discriminate the study groups.Mapping parameters in the thoracic skeletal muscles were able to discriminate between AVM and IIM patients. Best skeletal muscle parameters to identify IIM from AVM patients were reduced post-contrast T1 and increased extracellular volume (ECV), resulting in an area under the ROC curve (AUC) of 0.95 for post-contrast T1 and 0.96 for ECV. Conversely, myocardial mapping parameters did not discriminate IIM from AVM patients but increased native T1  and increased T2  could differentiate both patient groups from healthy controls.CMR myocardial mapping detects cardiac inflammation in AVM and IIM compared to normal myocardium in healthy controls but does not differentiate IIM from AVM. However, thoracic skeletal muscle mapping was able to accurately discern IIM from AVM. Myocarditis is commonly defined as an inflammatory injury to the myocardium that may result from a variety of causes, most frequently acute viral infection but also systemic inflammatory disease. Idiopathic inflammatory myopathy (IIM) is a group of chronic autoimmune systemic myositis, including polymyositis, dermatomyositis and inclusion body myositis . ClinicaCardiovascular magnetic resonance (CMR) T2-weighted and late gadolinium enhancement (LGE) sequences allow for non-invasive detection of myocarditis in 50% of patients with a troponin-positive episode of chest pain and absence of coronary artery disease. However, the underlying etiology remains unclear in 35% of these cases . New CMROur study aims to investigate the usefulness of combined T1 and T2 mapping in cardiac and skeletal muscles as a novel approach to differentiate IIM from AVM in the clinical setting.For this retrospective study, a total of 60 participants were included : 20 consecutive patients with AVM, 20 consecutive patients with IIM and 20 healthy subjects. AVM patients were included based on clinical guidelines and presented with recent onset chest pain, elevated troponin T and C-reactive protein (CRP), as well as absence of coronary artery disease on angiography, performed in case of acute coronary syndrome-like clinical presentation. Patients without cardiac troponin > 50 ng/ml or with onset of symptoms > 2 weeks before CMR or with prior myocardial infarction were excluded. IIM patients were included based on the elevation of skeletal muscle enzyme levels, evidence of myositis on skeletal muscle biopsy, electromyography (EMG) features of myositis and elevated cardiac troponins > 50 ng/ml at the time of CMR indicating cardiac involvement. Patients with > 2 weeks between troponin elevation and CMR, or with fever or flu-like syndrome in the past 6 months were excluded. Electrocardiogram (ECG) ST-elevation on admission was found in 9/20 of the AVM patients and 4/20 of the IIM patients and led to immediate coronary angiography to assess for coronary artery disease. In addition, 20 asymptomatic subjects without personal medical history or overt cardiovascular disease and normal clinical exam underwent CMR as healthy controls. The study was approved by the local ethics committee and written informed consent was obtained from all participants. The following laboratory test results were collected: hematocrit, NT-proBNP (pg/ml), troponin T (ng/ml), creatine phosphokinase  and CRP(mg/l). The delay between CMR and blood sampling was 4 ± 6 days in IIM patients and 1 ± 1 days in AVM patients. Blood sampling for the control group was performed at the time of CMR. Gender, age, body mass index (BMI) and cardiovascular risk factors were collected. Heart failure was defined by the presence of typical symptoms including breathlessness, fatigue accompanied by signs of elevated right and/or left filling pressures: dilated jugular veins, lower extremity edema, pulmonary edema and/or effusion. Studied IIM patients included: 7 necrotizing autoimmune myopathies, 5 anti-synthetase and 2 overlap syndromes, 3 polymyositis, 2 dermatomyositis and 1 inclusion body myositis.2, slice thickness = 6 mm, inter-slice gap = 1 mm. Temporal resolution was between 10 and 40 ms; 2) short- and long-axis LGE sequences acquired with a single shot inversion recovery sequence 7 to 10 min after injection of 0.2 mmol/kg of gadobenate dimeglumine  with the following parameters: acquisition matrix = 240 × 240, inversion time individually chosen on TI scout, repetition time = 347 ms, echo time = 1.18 ms, flip angle = 40°, pixel size = 1.46 × 1.46mm2, slice thickness = 8 mm, inter-slice gap = 0.8 mm; 3) Motion-corrected basal, mid-LV and apical short-axis Look-Locker inversion-recovery (MOLLI) T1 mapping sequence with a 5(3)3 scheme before and 15 min after intravenous contrast agent injection with the following parameters: acquisition matrix = 218 × 256, echo time = 1.12 ms, repetition time = 343.86 ms, flip angle = 35°, pixel size = 1.41 × 1.41mm2, slice thickness = 8 mm; 4) T2 mapping was performed in basal, mid-LV and apical short-axis slices using a 3-point T2-prepared bSSFP sequence before contrast injection with the following CMR parameters: acquisition matrix = 206 × 256, echo time = 0,24,55 ms, repetition time = 299.74 ms, flip angle = 35°, pixel size = 1.41 × 1.41mm2, slice thickness = 8 mm.All participants had CMR on a 1.5T magnet  with the following acquisition sequences: 1) balanced steady state free precession (bSSFP) cine imaging in short- and long-axis views with typical parameters: acquisition matrix = 216 × 256, repetition time = 51 ms, echo time = 1.19 ms, flip angle = 53°, pixel size = 1.48 × 1.48mmLeft ventricular (LV) and right ventricular (RV) volumes and ejection fraction (EF) as well as LV mass have been assessed based on standard short axis semi-automated endocardial and epicardial segmentation. Feature tracking was used to calculate LV and RV myocardial global longitudinal strain (GLS), averaged from 2 chamber and 4 chamber long axis cine views with a dedicated semi-automated software, as previously described . LongituEndocardial and epicardial contours were traced with motion-correction for every single TI-image on MOLLI images to exclude near wall blood, epicardial fat or areas presenting Gibbs artifacts. T1 maps were then calculated on basal and mid-LV short-axis slices for both native and post contrast images. Apical slices were not analyzed, due to higher prevalence of motion artifacts and risk of partial volume effect caused by obliquity and thinner wall. Myocardium was automatically segmented into AHA segments using the anterior right septal insertion mark as a reference. Whole-heart myocardial relaxation times were calculated as the mean of mid-LV and basal slices, including and excluding LGE-positive segments. The same analysis was performed for T2 mapping. To estimate thoracic muscle T1 and T2 values, regions of interest (ROI) were traced and adjusted for every TI or TE-image on each of the following skeletal muscles, if identified in the acquired field of view: pectoralis major, subscapularis, infraspinatus, upper arm and erector spinae muscles. The ROI was drawn on the first TI/TE-image by excluding perimuscular fat and intramuscular tendons as illustrated in Fig. p-value < 0.05 was regarded as significant. Multivariate analysis was used including age as a covariate to calculate age-adjusted p-values for cardiac volumes and mapping indices. Analysis was performed using GraphPad Prism  and Stata .Comparisons between IIM and AVM patients and controls were performed using non-parametric Mann-Whitney’s test for continuous variables and Fisher’s Exact Test for categorical variables. For multiple group comparisons , non-parametric Kruskal-Wallis test was used. Receiver operating characteristic (ROC) analysis was used to determine the most discriminating mapping parameter and cutoff values. A Baseline characteristics of the study population are shown in Table Biventricular volumes, functional parameters and strains are reported in Table Table Figure Different thoracic muscle groups had similar mapping parameters in healthy controls Fig. , except This study shows that CMR T1 mapping allows identification of myocardial involvement in IIM without significant differences in myocardial mapping parameters between IIM and AVM. In addition, in unclear cases of suspected myocarditis and CMR with no or few areas of LGE or presence of concomitant muscle weakness, dyspnea or dysphagia, T1 mapping in skeletal thoracic muscle – particularly post contrast T1 and ECV – allow reliable differentiation of acute viral myocarditis and IIM inflammatory myocarditis. To our knowledge, no study had yet compared AVM and IIM myocarditis using both myocardial and skeletal muscle T1 mapping. Yao et al.  showed tA large number of LGE positive segments were found in the AVM group, corresponding to regions with a high degree of myocardial inflammation and edema. IIM patients also had LGE but less frequently than AVM patients and less frequently in the epicardial layer. Whole heart T1 and T2 mapping parameters were not significantly different between AVM and IIM. However, there was a tendency for higher native T1 in AVM compared with IIM, when LGE positive segments were included, as LGE positive segments are known to result in higher native T1 values compared to LGE-negative segments . Our finIn addition to IIM, there are other systemic autoimmune diseases with cardiac involvement, such as systemic lupus erythematosus (SLE), sarcoidosis or systemic sclerosis. Native T1 and T2 mapping techniques are able to identify SLE patients from healthy controls , which mNative T1 was significantly different between the skeletal muscle groups, especially in the more peripherally located pectoralis and upper arm muscles. This may have explanations. First, CMR is focused on the heart, using a thoracic coil, and shimming will be less optimized in the periphery of the CMR field-of view. In addition, T1 shortening due to susceptibility might occur, especially in locations close to air near the body surface. Also, possible spill in from peri-muscular fat might occur in patients with thin muscles, affecting especially the pectoralis muscle due to its anatomic localization. These effects may be further aggravated by motion artefacts. Pectoralis muscles may be affected both by breathing and arm movement. Due to shortened T1 after gadolinium injection and due to relative compensation in the ECV formula (ratio), post contrast T1, and ECV were less sensitive to these effects. This may be similar for T2 with refocusing pulses in the SSFP-based sequence. However, post contrast T1, T2 and ECV in different thoracic skeletal muscle groups showed comparable values in healthy controls. Thus, all of the measured muscles can be used for measuring skeletal muscle relaxation time, as visualized on any standard CMR field of view. With these considerations kept in mind and for simplicity, post contrast T1, T2 and ECV may be measured in the best visualized muscle allowing to place the largest ROI excluding vessels, tendons and fat.p < 0.001) in longitudinal studies [A schematic clinical flow-chart on how mapping techniques might be used in patients with suspected AVM/IIM is proposed in Fig.  studies . Consequ studies  unlike A studies . WhetherThis study has several limitations. There is a relatively small patient population given the difficulty to recruit IIM patients with elevated cardiac troponins and CMR. Nevertheless, differentiation of acute viral and IIM myocarditis was highly significant using skeletal muscle mapping. Endomyocardial biopsy is not routinely performed in patients with non-complicated myocarditis in our center. In addition, even if all IIM patients had diagnosis proven by skeletal muscle biopsy and histology, there was no such data in the AVM group as there was no indication for biopsy of skeletal muscles in this group. Another limitation is that shimming is not optimized for skeletal muscles in typical CMR exams, potentially affecting native T1 to a higher degree than post contrast T1, ECV and T2 as discussed above. However, the latter three parameters did not differ significantly between different thoracic skeletal muscle groups when peri-muscular fat and intra-muscular tendons were carefully excluded.A combined investigation of myocardial and skeletal muscle CMR T1 mapping parameters allow accurate differentiation of AVM from IIM myocarditis by measuring post contrast T1 and ECV in the skeletal muscle. This approach could help in identifying patients with IIM-related cardiac involvement in patients referred to CMR for suspected AVM, allowing differential diagnosis, early IIM treatment and potentially lead to improved patient outcome.


While it is known that the heart remodels progressively with age, data characterizing the relationship between cardiac remodelling and function on physical function among the aged are limited.We investigated the association between left ventricular (LV) concentricity and LV function with handgrip strength  and timed-up-and-go test (for lower extremity function) among clinically asymptomatic elderly.0.67 (mass/end-diastolic volume0.67) and LV function by resting tissue Doppler imaging (TDI) performed at the septal and lateral mitral annulus, deriving myocardial systolic velocity (S), diastolic velocity (E) and ratio of E/A.In this community-based cohort of 28 patients free of known cardiac disease (mean age 73.8 ± 4) with preserved LV ejection fraction (mean LVEF 69.8 ± 6.4) and cardiac index (mean 3.1 ± 0.57), we assessed cardiac remodelling by cardiac MRI , lateral S , septal A , and between timed-up-and-go and LV concentricity , lateral E/A , septal A . By regression analysis, LV concentricity  (with adjustment for systolic blood pressure) and lateral E/A  were independently predictive of handgrip strength and timed-up-and-go respectively.These preliminary observations provide important insights into a possible link between subclinical alterations in cardiac structure and function and physical function, further study is required to clarify these findings with a view to preserve health and function amongst the elderly.