Telemetric Blood Pressure Assessment in Angiotensin II-Infused ApoE\u3csup\u3e-/-\u3c/sup\u3e Mice: 28 Day Natural History and Comparison to Tail-Cuff Measurements

Abdominal aortic aneurysm (AAA) is a disease of the aortic wall, which can progress to catastrophic rupture. Assessment of mechanical characteristics of AAA, such as aortic distensibility, may provide important insights to help identify at-risk patients and understand disease progression. While the majority of studies on this topic have focused on retrospective patient data, recent studies have used mouse models of AAA to prospectively evaluate the evolution of aortic mechanics. Quantification of aortic distensibility requires accurate measurement of arterial blood pressure, particularly pulse pressure, which is challenging to perform accurately in murine models. We hypothesized that volume/pressure tail-cuff measurements of arterial pulse pressure in anesthetized mice would have sufficient accuracy to enable calculations of aortic distensibility with minimal error. Telemetry devices and osmotic mini-pumps filled with saline or angiotensin-II were surgically implanted in male apolipoprotein-E deficient (ApoE-/-) mice. Blood pressure in the aortic arch was measured continuously via telemetry. In addition, simultaneous blood pressure measurements with a volume/pressure tail-cuff system were performed under anesthesia at specific intervals to assess agreement between techniques. Compared to controls, mice infused with angiotensin-II had an overall statistically significant increase in systolic pressure, with no overall difference in pulse pressure; however, pulse pressure did increase significantly with time. Systolic measurements agreed well between telemetry and tail-cuff (coefficient of variation = 10%), but agreement of pulse pressure was weak (20%). In fact, group-averaged pulse pressure from telemetry was a better predictor of a subject\u27s pulse pressure on a given day than a simultaneous tail-cuff measurement. Furthermore, these approximations introduced acceptable errors (15.1 ± 12.8%) into the calculation of aortic distensibility. Contrary to our hypothesis, we conclude that tail-cuff measures of arterial pulse pressure have limited accuracy. Future studies of aneurysm mechanics using the ApoE-/-/angiotensin-II model would be better in assuming pulse pressure profiles consistent with our telemetry findings instead of attempting to measure pulse pressure in individual mice

Characterizing the Temporal Evolution of Altered Cardiac Mechanics in Diet-Induced Obese Mice Using Cine DENSE CMR

Background Obesity and metabolic syndrome are associated with increased risk of cardiovascular disease. Research suggests that altered cardiac mechanics (i.e., reduced strains, torsion, and synchrony of contraction) are present in obesity; yet, the causes of this mechanical dysfunction and its relationship to other sequelae of obesity (e.g., hypertension and elevated blood glucose) are not well understood. We hypothesize that diet-induced obesity in mice leads to reductions in measures of left ventricular (LV) mechanics, which develop in acute response to the onset of hyperglycemia, hypertension, and ventricular remodeling. Methods Twenty 4-week-old C57BL/6J mice were randomized (n = 10 per group) to either a high-fat (60% kcal from fat) or sucrose-matched low-fat (10% kcal from fat) diet for 28 weeks. After 4 weeks and every 6 weeks thereafter, LV mechanics were quantified using cine displacement encoding with stimulated echoes (DENSE) on a 7T ClinScan MRI (Bruker, Ettlingen, Germany) with a 4-element phased array cardiac coil. Three short-axis and two long-axis slices were acquired with 13-20 frames per cardiac cycle. Semi-automated post-processing was performed using custom software in MATLAB (Mathworks, Natick, MA). Additionally, systolic blood pressure (via tail cuff measurement) and fasting blood glucose were assessed every 4 weeks on staggered schedules. Results Mice on the high-fat diet became obese relative to the low-fat controls (49.9 vs. 29.2 g, respectively, by week 28;). Fasting blood glucose was elevated in the high-fat group (202 vs. 112 mg/dL; p \u3c 0.05) starting from the earliest measurement (week 7 on diet), whereas significant differences in LV mass (88 vs. 79 mg) and systolic blood pressure (172 vs. 162 mmHg) developed much later (weeks 22 and 25 on diet, respectively). Significant reductions in peak LV radial (15%) and circumferential (8%) strains and reduced contractile synchrony were detected in the high-fat group for the first time in week 28. A 10% reduction in peak torsion was also observed at that time, but did not reach statistical significance (p = 0.075). There were no differences in LV cavity volumes or ejection fraction. Conclusions Diet-induced obesity in mice is associated with reduced left ventricular mechanics. This dysfunction develops long after the manifestation of hyperglycemia in this model, which suggests that chronic alterations in glucose/insulin levels and/or signaling may contribute more to cardiac contractile dysfunction than acute elevations. Late development of concentric ventricular hypertrophy and hypertension prior to suppressed cardiac mechanics also suggests an important role of these processes in the reduced ventricular function

Reproducibility of cine displacement encoding with stimulated echoes (DENSE) cardiovascular magnetic resonance for measuring left ventricular strains, torsion, and synchrony in mice

BACKGROUND: Advanced measures of cardiac function are increasingly important to clinical assessment due to their superior diagnostic and predictive capabilities. Cine DENSE cardiovascular magnetic resonance (CMR) is ideal for quantifying advanced measures of cardiac function based on its high spatial resolution and streamlined post-processing. While many studies have utilized cine DENSE in both humans and small-animal models, the inter-test and inter-observer reproducibility for quantification of advanced cardiac function in mice has not been evaluated. This represents a critical knowledge gap for both understanding the capabilities of this technique and for the design of future experiments. We hypothesized that cine DENSE CMR would show excellent inter-test and inter-observer reproducibility for advanced measures of left ventricular (LV) function in mice. METHODS: Five normal mice (C57BL/6) and four mice with depressed cardiac function (diet-induced obesity) were imaged twice, two days apart, on a 7T ClinScan MR system. Images were acquired with 15-20 frames per cardiac cycle in three short-axis (basal, mid, apical) and two long-axis orientations (4-chamber and 2-chamber). LV strain, twist, torsion, and measures of synchrony were quantified. Images from both days were analyzed by one observer to quantify inter-test reproducibility, while inter-observer reproducibility was assessed by a second observer\u27s analysis of day-1 images. The coefficient of variation (CoV) was used to quantify reproducibility. RESULTS: LV strains and torsion were highly reproducible on both inter-observer and inter-test bases with CoVs ≤ 15%, and inter-observer reproducibility was generally better than inter-test reproducibility. However, end-systolic twist angles showed much higher variance, likely due to the sensitivity of slice location within the sharp longitudinal gradient in twist angle. Measures of synchrony including the circumferential (CURE) and radial (RURE) uniformity of strain indices, showed excellent reproducibility with CoVs of 1% and 3%, respectively. Finally, peak measures (e.g., strains) were generally more reproducible than the corresponding rates of change (e.g., strain rate). CONCLUSIONS: Cine DENSE CMR is a highly reproducible technique for quantification of advanced measures of left ventricular cardiac function in mice including strains, torsion and measures of synchrony. However, myocardial twist angles are not reproducible and future studies should instead report torsion

Assessment of intra- and inter-ventricular cardiac dyssynchrony in patients with repaired Tetralogy of Fallot: a cardiac magnetic resonance study

Using radiative magnetohydrodynamic simulations of the magnetized solar photosphere and detailed spectro-polarimetric diagnostics with the Fe I 6301.5 Å and 6302.5 Å photospheric lines in the local thermodynamic equilibrium approximation, we model active solar granulation as if it was observed at the solar limb. We analyze general properties of the radiation across the solar limb, such as the continuum and the line core limb darkening and the granulation contrast. We demonstrate the presence of profiles with both emission and absorption features at the simulated solar limb, and pure emission profiles above the limb. These profiles are associated with the regions of strong linear polarization of the emergent radiation, indicating the influence of the intergranular magnetic fields on the line formation. We analyze physical origins of the emission wings in the Stokes profiles at the limb, and demonstrate that these features are produced by localized heating and torsional motions in the intergranular magnetic flux concentrations

High Resolution Cine Displacement Encoding with Stimulated Echoes (DENSE) at 3T with Navigator Feedback for Quantification of Cardiac Mechanics

Background: Measures of cardiac mechanics such as myocardial wall strain are better predictors of outcomes in patients with heart disease compared to traditional clinical measures and ejection fraction. Cine displacement encoding with stimulated echoes (DENSE) is an ideal method for quantifying cardiac motion which encodes tissue displacement in the phase of the MR signal and provides pixel-level resolution for quantifying cardiac mechanics. To date, DENSE has been implemented with resolution limited to 2-3 pixels across the myocardium. While this resolution is higher than most other techniques for quantifying cardiac mechanics, it may limit the ability of DENSE to quantify finer details such as transmural strains (subendocardial, midmyocardial and subepicardial) and right ventricular mechanics. We hypothesized that it is possible to efficiently increase the resolution of DENSE by a factor of 4 utilizing a navigator feedback system. Methods: 10 subjects (age 27 ± 3) with normal ECG and no history of cardiovascular disease were consented. A 3.0T Siemens Tim Trio with a 6-element chest and 24-element spine coil was configured with a navigator feedback system. The feedback system projected the navigator image of the diaphragm to the subject in real time to optimize breathold position. Standard resolution 2D cine DENSE was acquired with: 6 spiral interleaves, FOV = 340 mm, matrix = 96 × 96, thickness = 8 mm, TE/TR = 1.08/17, flip angle = 20, averages = 1, navigator acceptance window = ± 3 mm. High resolution 2D cine DENSE images were acquired by quadrupling the number of spirals to 24, increasing the matrix to 256 × 256, and increasing the averages to 3. Three short- and two long-axis images were acquired with each technique. Left ventricular strains and torsion were compared between the techniques using Bland-Altman. Results: The high resolution images took 11 times longer to acquire but the navigator feedback system provided good efficiency (69 ± 9%) for a total acquisition time of roughly 5 minutes per slice. The high resolution images had excellent quality with a noticeable improvement over standard resolution. There was a systematic but negligible difference between standard and high resolution data for circumferential and longitudinal strains. Radial strains showed the largest differences consistent with a systematic under-estimation of radial strain from standard resolution DENSE. Torsion was not significantly different between the two methods. Conclusions: High resolution cine DENSE MRI with navigator feedback is feasible at 3T and produces high quality images with 4 times the resolution of standard DENSE. Left ventricular circumferential strains, longitudinal strains, and torsion showed negligible differences between high and low resolution DENSE. Radial strains were significantly different, potentially due to better accuracy with high resolution DENSE due to the increased number of pixels within the thickness of the myocardial wall

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