Cardiovascular magnetic resonance feature tracking in small animals – a preliminary study on reproducibility and sample size calculation

Background Cardiovascular magnetic resonance feature tracking (CMR-FT) is a novel tissue tracking technique developed for noninvasive assessment of myocardial motion and deformation. This preliminary study aimed to evaluate the observer’s reproducibility of CMR-FT in a small animal (mouse) model and define sample size calculation for future trials. Methods Six C57BL/6 J mice were selected from the ongoing experimental mouse model onsite and underwent CMR with a 3 Tesla small animal MRI scanner. Myocardial deformation was analyzed using dedicated software (TomTec, Germany) by two observers. Left ventricular (LV) longitudinal, circumferential and radial strain (EllLAX, EccSAX and ErrSAX) were calculated. To assess intra-observer agreement data analysis was repeated after 4 weeks. The sample size required to detect a relative change in strain was calculated. Results In general, EccSAX and EllLAX demonstrated highest inter-observer reproducibility (ICC 0.79 (0.46–0.91) and 0.73 (0.56–0.83) EccSAX and EllLAX respectively). In contrast, at the intra-observer level EllLAX was more reproducible than EccSAX (ICC 0.83 (0.73–0.90) and 0.74 (0.49–0.87) EllLAX and EccSAX respectively). The reproducibility of ErrSAX was weak at both observer levels. Preliminary sample size calculation showed that a small study sample (e.g. ten animals to detect a relative 10% change in EccSAX) could be sufficient to detect changes if parameter variability is low. Conclusions This pilot study demonstrates good to excellent inter- and intra-observer reproducibility of CMR-FT technique in small animal model. The most reproducible measures are global circumferential and global longitudinal strain, whereas reproducibility of radial strain is weak. Furthermore, sample size calculation demonstrates that a small number of animals could be sufficient for future trials

Cardiovascular magnetic resonance feature tracking in pigs: a reproducibility and sample size calculation study

Cardiovascular magnetic resonance feature tracking (CMR-FT) is a novel technique for non-invasive assessment of myocardial motion and deformation. Although CMR-FT is standardized in humans, literature on comparative analysis from animal models is scarce. In this study, we measured the reproducibility of global strain under various inotropic states and the sample size needed to test its relative changes in pigs. Ten anesthetized healthy Landrace pigs were investigated. After baseline (BL), two further steps were performed: (I) dobutamine-induced hyper-contractility (Dob) and (II) verapamil-induced hypocontractility (Ver). Global longitudinal (GLS), circumferential (GCS) and radial strain (GRS) were assessed. This study shows a good to excellent inter- and intra-observer reproducibility of CMR-FT in pigs under various inotropic states. The highest inter-observer reproducibility was observed for GLS at both BL (ICC 0.88) and Ver (ICC 0.79). According to the sample size calculation for GLS, a small number of animals could be used for future trials

Analyse der linksventrikulären Strain mittels kardiovaskulärer Magnetresonanztomographie (CMR-FT): eine Studie an Landrassenschweinen

Background: Left ventricular (LV) strain imaging is a validated imaging technique able to quantify myocardial function. While the assessment of LV strain is an established clinical routine in echocardiography, cardiovascular magnetic resonance (CMR) LV strain analysis is, instead, a newly emerging method. In specific, CMR feature tracking (CMR-FT) is a promising tracking technique for tissue developed for evaluating myocardial movement and deformation. However, to what extent CMR-FT LV systolic strain reflects the LV mechanical function of the heart still needs to be fully understood. For this reason, the aim of our study was to compare the non-invasive CMR-FT LV strain against invasive hemodynamic parameters representative of the mechanical function of the heart. This includes the cardiac index (CI), cardiac power output (CPO) and end-systolic elastance (Ees), and the data was compared by analyzing them at different inotropic states (hypercontractility and hypocontractility). Methods: Ten healthy Landrace pigs were instrumented, intubated, mechanically ventilated, and transported to the 3-Tesla MRI facility. After baseline measurements (BL), two steps were performed: I) dobutamine-induced hyper-contractility (Dob) and II) verapamil-induced hypocontractility (Ver). At each step, MRI images were acquired at short axis (SAX), 2Ch, 3Ch and 4Ch views. The software MEDIS was utilized to assess the LV mechanical parameters such as global longitudinal strain (GLS), global circumferential strain (GCS) and global radial strain (GRS). Additionally, we calculated the sample size required for the detection of a relative change in baseline strain. Results: Dob demonstrated a noteworthy increased heart rate, CI, CPO and Ees, while Ver decreased them. GLS, GCS and GRS accordingly increased (in absolute value) during Dob infusion, while GLS and GCS decreased (in absolute value) during Ver. Linear regression analysis demonstrated a moderate correlation between GLS, GCS and LV hemodynamic parameters, while GRS correlated poorly. The correlations were significantly improved by indexing global strain parameters for indirect afterload measures such as mean aortic pressure or wall stress. Conclusions: Global longitudinal and circumferential strain moderately correlate with LV invasive parameters such as cardiac power output, cardiac index and end-systolic elastance under various inotropic states. Indexing strain parameters for indirect afterload measures greatly improves this correlation. CMR FT LV strain imaging may be a useful tool in the clinical routine to characterize the LV hemodynamics in patients experiencing different degrees of LV dysfunction.Hintergrund: Die Bildgebung bei linksventrikulärer (LV) Strain ist eine validierte Bildgebungstechnik, die in der Lage ist, die myokardiale Funktion zu quantifizieren. Während die echokardiographische Beurteilung des LV-Strain eine etablierte klinische Routine ist, ist die Analyse des LV-Strain mittels kardiovaskulärer Magnetresonanz (CMR) stattdessen eine neu aufkommende Methode. Im Besonderen ist die CMR-Feature Tracking (CMR-FT) eine vielversprechende Gewebeverfolgungstechnik, die für die Beurteilung der myokardialen Bewegung und Deformation entwickelt wurde. Inwieweit der systolische LV-Strain der CMR FT die mechanische Funktion des Herzens widerspiegelt, muss jedoch noch vollständig verstanden werden. Aus diesem Grund war es das Ziel unserer Studie, die nicht-invasive CMR-FT LV-Strain mit invasiven hämodynamischen Parametern zu vergleichen, die für die mechanische Funktion des Herzens repräsentativ sind, wie z.B. Herzindex (CI), Herzleistung (CPO) und end-systolische Elastanz (Ees), indem sie bei verschiedenen inotropen Zuständen analysiert wurden. Methoden: Zehn gesunde Landrace-Schweine wurden intubiert, mechanisch beatmet und in die 3-Tesla-MRT-Einrichtung transportiert. Nach den Basislinienmessungen (BL) wurden zwei Schritte durchgeführt: I) dobutamininduzierte Hyperkontraktilität (Dob) und II) verapamilinduzierte Hypokontraktilität (Ver). In jedem Schritt wurden MRT-Bilder in Kurzachsen- (SAX), 2Ch, 3Ch und 4Ch-Ansicht aufgenommen. Die Software MEDIS wurde zur Beurteilung der globalen Längs- (GLS), Zirkumferentiell- (GCS) und Radial Strain (GRS) verwendet. Die zum Nachweis einer relativen Änderung der BL-Strain erforderliche Probengröße wurde berechnet. Ergebnisse: Dob erhöhte signifikant die Herzfrequenz, CI, CPO und Ees, während Ver sie verringerte. GLS, GCS und GRS stiegen dementsprechend (im absoluten Wert) während der Dob-Infusion an, während GLS und GCS (im absoluten Wert) während der Ver abnahmen. Die lineare Regressionsanalyse zeigte eine mäßige Korrelation zwischen GLS, GCS und den hämodynamischen LV-Parametern, während GRS schlecht korrelierte. Die Indizierung globaler Strain Parameter für indirekte Messungen der Nachlast, wie z.B. mittlerer Aortendruck oder Wandspannung, verbesserte diese Korrelationen signifikant. Schlussfolgerungen: Die globale Längs- und Zirkumferentiell Strain korreliert mäßig mit LV invasiven Parametern wie der kardialen Leistung, dem kardialen Index und der end systolischen Elastanz unter verschiedenen inotropen Zuständen. Die Indexierung von Strain Parametern für indirekte Messungen der Nachlast verbessert diese Korrelation erheblich. Die CMR-FT-LV-Strain kann in der klinischen Routine ein nützliches Instrument zur Charakterisierung der LV-Hämodynamik bei Patienten mit unterschiedlichem Grad der LV Dysfunktion sein

Hemodynamic mechanisms of experimental and clinical heart failure: a translational perspective

Main focus of this dissertation is the investigation and further characterization of invasive and non-invasive indices of LV function and cardiovascular hemodynamics both in preclinical (Sus scrofa) as well as clinical HF. Following topics were addressed in the current work: 1. The correlation between LV CPO, as clinically relevant index of external LV work, and the conductance catheter-derived LV SW over a wide range of contractility states in experimental acute heart failure in Landrace pigs. 2. The reproducibility and reference values of global LV strain indices assessed via a novel CMR-FT analysis under various inotropic states in Landrace pigs. 3. The impact of indexing CMR-derived LV strain parameters for indirect measures of afterload on their correlation with invasive hemodynamic indices in experimental acute heart failure in Landrace pigs. 4. The impact on LV contractility of a novel, inhalable, cardiac-specific nanocarrier delivering a LTCC-modulating peptide in experimental CHF in mice and Landrace pigs. 5. The assessment of LV hemodynamics with non-invasive and invasive techniques for a structured weaning of CS patients undergoing MVS with the Impella device

Video Kinematic Evaluation: new insights on the cardiac mechanical function

The cardiac mechanical function plays a critical role in governing and regulating its performance under both normal and pathological conditions. The left ventricle has historically received more attention in both congenital and acquired heart diseases and was considered as the mainstay of normal hemodynamics. However, over the past few decades, there has been increasing recognition of the pivotal role of the right ventricle in determining functional performance status and prognosis in multiple conditions. Nonetheless, the ventricles should not be considered separately as they share the septum, are encircled with common myocardial fibers and are surrounded by the pericardium. Thus, changes in the filling of one ventricle may alter the mechanical function of its counterpart. This ventricular interdependence remains even after the removal of the pericardium because of constrictive pericarditis or during open chest surgery. Interestingly, during open chest surgery, only the right ventricle mechanical activity is visually checked by the surgeon and cardiologist due to the absence of an intraoperative imaging technique able to evaluate its complex function. Noteworthy, most of the imaging techniques available to clinicians are established for the assessment of the left ventricle, with the ejection fraction being the most used parameter. However, this value is a measure of global systolic function which comes short in identifying regional myocardial impairment and the mechanical contraction. Therefore, new approaches are needed to deeply investigate the mechanics of both ventricles and correctly assess the cardiac mechanical performance. In this thesis, I studied the mechanical function of the left ventricle through different modalities of cardiac magnetic resonance and employed an innovative imaging technique for the assessment of the right ventricle mechanical function during open chest surgery

Low-dose dobutamine cardiovascular magnetic resonance segmental strain study of early phase of intramyocardial hemorrhage rats

BACKGROUND: This study investigates the segmental myocardial strain of the early phase of intramyocardial hemorrhage (IMH) caused by reperfused myocardial infarction (MI) in rats by low-dose dobutamine (LDD) cardiovascular magnetic resonance (CMR) feature-tracking. METHODS: Nine sham rats and nine rats with 60-min myocardial ischemia followed by 48-h reperfusion were investigated using CMR, including T2*-mapping sequence and fast imaging with steady-state precession (FISP)-cine sequence. Another FISP-cine sequence was acquired after 2 min of dobutamine injection; the MI, IMH, and Non-MI (NMI) areas were identified. The values of peak radial strains (PRS) and peak circumferential strains (PCS) of the MI, IMH and NMI segments were acquired. The efficiency of PRS and PCS (EPRS and EPCS, respectively) were calculated on the basis of the time of every single heartbeat. RESULTS: The PRS, PCS, EPRS, and EPCS of the sham group increased after LDD injection. However, the PRS, PCS, EPRS, and EPCS of the IMH segment did not increase. Moreover, the PRS and PCS of the MI and NMI segments did not increase, but the EPRS and EPCS of these segments increased. The PRS, PCS, EPRS, and EPCS of the IMH segment were lower than those of the MI and NMI segments before and after LDD injection, but without a significant difference between MI segment and NMI segment before and after LDD injection. CONCLUSIONS: LDD could help assess dysfunctions in segments with IMH, especially using the efficiency of strain. IMH was a crucial factor that decreased segmental movement and reserved function

Using a Respiratory Navigator Significantly Reduces Variability When Quantifying Left Ventricular Torsion with Cardiovascular Magnetic Resonance

Background: Left ventricular (LV) torsion is an important indicator of cardiac function that is limited by high inter-test variability (50% of the mean value). We hypothesized that this high inter-test variability is partly due to inconsistent breath-hold positions during serial image acquisitions, which could be significantly improved by using a respiratory navigator for cardiovascular magnetic resonance (CMR) based quantification of LV torsion. Methods: We assessed respiratory-related variability in measured LV torsion with two distinct experimental protocols. First, 17 volunteers were recruited for CMR with cine displacement encoding with stimulated echoes (DENSE) in which a respiratory navigator was used to measure and then enforce variability in end-expiratory position between all LV basal and apical acquisitions. From these data, we quantified the inter-test variability of torsion in the absence and presence of enforced end-expiratory position variability, which established an upper bound for the expected torsion variability. For the second experiment (in 20 new, healthy volunteers), 10 pairs of cine DENSE basal and apical images were each acquired from consecutive breath-holds and consecutive navigator-gated scans (with a single acceptance position). Inter-test variability of torsion was compared between the breath-hold and navigator-gated scans to quantify the variability due to natural breath-hold variation. To demonstrate the importance of these variability reductions, we quantified the reduction in sample size required to detect a clinically meaningful change in LV torsion with the use of a respiratory navigator. Results: The mean torsion was 3.4 ± 0.2°/cm. From the first experiment, enforced variability in end-expiratory position translated to considerable variability in measured torsion (0.56 ± 0.34°/cm), whereas inter-test variability with consistent end-expiratory position was 57% lower (0.24 ± 0.16°/cm, p \u3c 0.001). From the second experiment, natural respiratory variability from consecutive breath-holds translated to a variability in torsion of 0.24 ± 0.10°/cm, which was significantly higher than the variability from navigator-gated scans (0.18 ± 0.06°/cm, p = 0.02). By using a respiratory navigator with DENSE, theoretical sample sizes were reduced from 66 to 16 and 26 to 15 as calculated from the two experiments. Conclusions: A substantial portion (22-57%) of the inter-test variability of LV torsion can be reduced by using a respiratory navigator to ensure a consistent breath-hold position between image acquisitions

PROPERTIES AND OPTIMIZATION OF RESPIRATORY NAVIGATOR GATING FOR SPIRAL CINE DENSE CARDIAC MRI

Cardiac magnetic resonance (MR) imaging can non-invasively assess heart function. Displacement encoding with stimulated echoes (DENSE) is an advanced cardiac MR imaging technique that measures tissue displacement and can be used to quantify cardiac mechanics (e.g. strain and torsion). When combined with clinical risk factors, cardiac mechanics have been shown to be better predictors of mortality than traditional measures of heart function. End-expiratory breath-holds are typically used to minimize respiratory motion artifacts. Unfortunately, requiring subjects to breath-hold introduces limitations with the duration of image acquisition and quality of data acquired, especially in patients with limited ability to hold their breath. Thus, DENSE acquisitions often require respiratory navigator gating, which works by measuring the diaphragm during normal breathing and only acquiring data when the diaphragm is within a pre-defined acceptance window. Unfortunately, navigator gating results in long scan durations due to inconsistent breathing patterns. Also, the navigator echo can be used in different ways to accept or reject image data, which creates several navigator configuration options. Each respiratory navigator configuration has distinct advantages and disadvantages that directly affect scan duration and image quality, which can affect derived cardiac mechanics. Scan duration and image quality need to be optimized to improve the clinical utility of DENSE. Thus, the goal of this project was to optimize those parameters. To accomplish this goal, we set out to complete 3 aims: 1) understand how respiratory gating affects the reproducibility of measures of cardiac mechanics, 2) determine the optimal respiratory navigator configuration, and 3) reduce scan duration by developing and using an interactive videogame to optimize navigator efficiency. Aim 1 of this project demonstrated that the variability in torsion, but not strain, could be significantly reduced through the use of a respiratory navigator compared to traditional breath-holds. Aim 2 demonstrated that, among the configuration options, the dual-navigator configuration resulted in the best image quality compared to the reference standard (traditional breath-holds), but also resulted in the longest scan duration. In Aim 3, we developed an interactive breathing-controlled videogame and demonstrated that its use during cardiac MR can significantly reduce scan duration compared to traditional free-breathing and also led to a small improvement in signal-to-noise ratio of the acquired images. In summary, respiratory navigator gating with DENSE 1) reduces the variability in measured LV torsion, 2) results in the best image quality with the dual-navigator configuration, and 3) results in significantly shorter scan durations through the use of an interactive videogame. Selecting the optimal navigator configuration and using an interactive videogame can improve the clinical utility of DENSE