Results of our study reveal that post-processing approach to GLS matters with respect to the reproducibility of measurements and detection of effective difference in GLS between controls and patients. We demonstrate that standardization of GLS post-processing helps to reduce the random component of variability, introduced by inconsistencies between and within observers, while fixed systematic inter-vendor bias due to vendor related differences in image processing algorithms remained. We further show that the greater precision of measurements affords greater effect size, and as thus, improved discrimination between controls and subgroups of patients, which was not vendor-dependent. Results of our study provide a proof of concept that standardization of GLS measurements is an essential step in ensuring the reliable quantification of myocardial deformation, between different observers, users and across vendors.
Previous studies leading up to the present work have highlighted the differing normal values as well as the results for intra- and interobserver reproducibility, as well as between vendors and centres (summarised in Table 1S from PMID:19789193) . In summary, the reported intraobserver CV ranges between 5.2–12.3%, whereas interobserver CV 10.9–15.4%, and our initial results agree well with these previous reports. However, we have shown that by following the standardization protocol considerably improves reproducibility of measurements, in the study group as a whole, as well as subgroups. By employing a standardization protocol, CMR-FT can become an objective and reproducible method for the quantification of LV deformation. Whereas the burden of contour manipulation may at first appear substantial, we have narrowed this down to a few essential and systematic steps, predictable of failure of tracking, as well as vendor-specific contour placement, which has proactively served to considerable improvement. This information is important as it may guide the necessary optimization steps of CMR-FT softwares, in order to adequately serve the clinical routine. Diversity of normal values is often noted limitation of CMR-FT, yet the range of the thus-far reported mean values is admittedly narrow (19–21.3%, Table 1S), also reproduced by the recent metanalysis by Vo et al., 20.1% . Majority of the previous studies used TomTec based software [6, 7], a product using the same tracking algorithm as the MEDIS software, and our MEDIS derived values in controls reproduce these previous reports. The systematically higher measurements with CVI42 signal a very different image-processing approach; yet the high inter-vendor agreement of measurements suggests that although the softwares may be employing different algorithms, they track similar features of myocardial deformation. The benefits of standardization can further be seen through marked improvement of CV and ICC and Bland Altman plots, reflecting the effect of harmonization for both intra- and inter-observer variability. Reduction of the mean differences and limits of agreement translate into smaller dispersion of the GLS measurements, which is greater for interobserver reproducibility. Applying the standardized steps improved results for both vendors; vendor-specific steps clearly helped to reduce intervendor bias, again communicating a random variability component or, in other words, the many ways in which different observers could potentially use the different softwares. Our findings emphasize the role of clear and documented instructions and their unconditional implementation, in support of multi-user transferability in routine clinical practice.
The detection of early disease relies on precision in the technique, which can control for misclassification from healthy subjects. The patients and groups in our study were selected to be representative of the common clinical scenarios, where employment of GLS is known to be complementary to the assessment of global LV function, e.g. the mid-range LV-EF 30–50% . Compared to controls, both patient groups were older and had significantly but similarly reduced global systolic function. In both groups, GLS values were significantly lower in comparison to controls. Of note, comparative GLS measurements between IHD and DCM group revealed significantly lower GLS in the DCM group (p < 0.001). This is an important observation, which is in part explained by considerably higher LV volumes in DCM group, indicating the presence of global remodelling and consequently, operation at much higher loading. In the IHD group, GLS is reduced considerably, but only owing to severe regional impairment, whereas the preserved myocardium at first compensates with hypertrophic response and not change of loading [1, 18]. Given the rather homogenous presentation of cases within the model disease groups, the AUC for separation of patient groups from healthy controls were excellent before and after standardization, although additional improvement remains notable.
The introduction of CMR-FT was long hailed as a much-needed clinical application that reuses the routine cine acquisitions, while reducing the need for additional imaging that encode the changes with myocardial deformation, such as tagging. The overall viability of this technology appeared to depend on the availably of a quick, sleek and foremost accurate offline postprocessing, which resulted in offspring of several dedicated software products for CMR-FT. Yet the results of CMR-FT analyses vary from vendor to vendor and remain highly observer dependent. Several solutions were proposed, foremost the averaging of results of repeated analyses for increasing intra-vendor reproducibility . Our results reveal that benefit of such solution is likely dubious, the doubling or tripling of analysis time notwithstanding, as the source of high variability primarily arise from the tracking failure of automatically detected (auto-) contours, which cannot be improved by repetition, but manipulation of contour placement on post-processed SSFP images. In our study, this approach turned out to influence most strongly the accuracy of CMR-FT and several reasons underlie this observation. There are many independent variables that cannot be improved by repetitive tracking including image quality, frame rate, slice geometry (e.g. cutting through the papillary muscles), observer and centre experience. Image quality will suffer with poor breath-capacity, mitral annular calcification, pericardial effusion, mis-triggering, low frame rate and imperfect slice positioning, and will result in poor auto-tracking due to difficult endo- and epicardial border definition and misallocation of placed boundary points. Institutional structures mandating standardised approaches and providing adequate training will have high impact on reproducibility and precision.