Quantitative Gadolinium-Free Cardiac Fibrosis Imaging in End Stage Renal Disease Patients Reveals A Longitudinal Correlation with Structural and Functional Decline.

Patients with end stage renal disease (ESRD) suffer high mortality from arrhythmias linked to fibrosis, but are contraindicated to late gadolinium enhancement magnetic resonance imaging (MRI). We present a quantitative method for gadolinium-free cardiac fibrosis imaging using magnetization transfer (MT) weighted MRI, and probe correlations with widely used surrogate markers including cardiac structure and contractile function in patients with ESRD. In a sub-group of patients who returned for follow-up imaging after one year, we examine the correlation between changes in fibrosis and ventricular structure/function. Quantification of changes in MT revealed significantly greater fibrotic burden in patients with ESRD compared to a healthy age matched control cohort. Ventricular mechanics, including circumferential strain and diastolic strain rate were unchanged in patients with ESRD. No correlation was observed between fibrotic burden and concomitant measures of either circumferential or longitudinal strains or strain rates. However, among patients who returned for follow up examination a strong correlation existed between initial fibrotic burden and subsequent loss of contractile function. Gadolinium-free myocardial fibrosis imaging in patients with ESRD revealed a complex and longitudinal, not contemporary, association between fibrosis and ventricular contractile 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 < 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.

Right Ventricular Strain, Torsion, and Dyssynchrony in Healthy Subjects Using 3D Spiral Cine DENSE Magnetic Resonance Imaging.

Mechanics of the left ventricle (LV) are important indicators of cardiac function. The role of right ventricular (RV) mechanics is largely unknown due to the technical limitations of imaging its thin wall and complex geometry and motion. By combining 3D Displacement Encoding with Stimulated Echoes (DENSE) with a post-processing pipeline that includes a local coordinate system, it is possible to quantify RV strain, torsion, and synchrony. In this study, we sought to characterize RV mechanics in 50 healthy individuals and compare these values to their LV counterparts. For each cardiac frame, 3D displacements were fit to continuous and differentiable radial basis functions, allowing for the computation of the 3D Cartesian Lagrangian strain tensor at any myocardial point. The geometry of the RV was extracted via a surface fit to manually delineated endocardial contours. Throughout the RV, a local coordinate system was used to transform from a Cartesian strain tensor to a polar strain tensor. It was then possible to compute peak RV torsion as well as peak longitudinal and circumferential strain. A comparable analysis was performed for the LV. Dyssynchrony was computed from the standard deviation of regional activation times. Global circumferential strain was comparable between the RV and LV (-18.0% for both) while longitudinal strain was greater in the RV (-18.1% vs. -15.7%). RV torsion was comparable to LV torsion (6.2 vs. 7.1 degrees, respectively). Regional activation times indicated that the RV contracted later but more synchronously than the LV. 3D spiral cine DENSE combined with a post-processing pipeline that includes a local coordinate system can resolve both the complex geometry and 3D motion of the RV.

Optimal configuration of respiratory navigator gating for the quantification of left ventricular strain using spiral cine displacement encoding with stimulated echoes (DENSE) MRI.

PURPOSE: To determine the optimal respiratory navigator gating configuration for the quantification of left ventricular strain using spiral cine displacement encoding with stimulated echoes (DENSE) MRI. MATERIALS AND METHODS: Two-dimensional spiral cine DENSE was performed on a 3 Tesla MRI using two single-navigator configurations (retrospective, prospective) and a combined "dual-navigator" configuration in 10 healthy adults and 20 healthy children. The adults also underwent breathhold DENSE as a reference standard for comparisons. Peak left ventricular strains, signal-to-noise ratio (SNR), and navigator efficiency were compared. Subjects also underwent dual-navigator gating with and without visual feedback to determine the effect on navigator efficiency. RESULTS: There were no differences in circumferential, radial, and longitudinal strains between navigator-gated and breathhold DENSE (P = 0.09-0.95) (as confidence intervals, retrospective: [-1.0%-1.1%], [-7.4%-2.0%], [-1.0%-1.2%]; prospective: [-0.6%-2.7%], [-2.8%-8.3%], [-0.3%-2.9%]; dual: [-1.6%-0.5%], [-8.3%-3.2%], [-0.8%-1.9%], respectively). The dual configuration maintained SNR compared with breathhold acquisitions (16 versus 18, P = 0.06). SNR for the prospective configuration was lower than for the dual navigator in adults (P = 0.004) and children (P < 0.001). Navigator efficiency was higher (P < 0.001) for both retrospective (54%) and prospective (56%) configurations compared with the dual configuration (35%). Visual feedback improved the dual configuration navigator efficiency to 55% (P < 0.001). CONCLUSION: When quantifying left ventricular strains using spiral cine DENSE MRI, a dual navigator configuration results in the highest SNR in adults and children. In adults, a retrospective configuration has good navigator efficiency without a substantial drop in SNR. Prospective gating should be avoided because it has the lowest SNR. Visual feedback represents an effective option to maintain navigator efficiency while using a dual navigator configuration. LEVEL OF EVIDENCE: 2 J. Magn. Reson. Imaging 2017;45:786-794.

An interactive videogame designed to improve respiratory navigator efficiency in children undergoing cardiovascular magnetic resonance.

BACKGROUND: Advanced cardiovascular magnetic resonance (CMR) acquisitions often require long scan durations that necessitate respiratory navigator gating. The tradeoff of navigator gating is reduced scan efficiency, particularly when the patient's breathing patterns are inconsistent, as is commonly seen in children. We hypothesized that engaging pediatric participants with a navigator-controlled videogame to help control breathing patterns would improve navigator efficiency and maintain image quality. METHODS: We developed custom software that processed the Siemens respiratory navigator image in real-time during CMR and represented diaphragm position using a cartoon avatar, which was projected to the participant in the scanner as visual feedback. The game incentivized children to breathe such that the avatar was positioned within the navigator acceptance window (±3 mm) throughout image acquisition. Using a 3T Siemens Tim Trio, 50 children (Age: 14 ± 3 years, 48 % female) with no significant past medical history underwent a respiratory navigator-gated 2D spiral cine displacement encoding with stimulated echoes (DENSE) CMR acquisition first with no feedback (NF) and then with the feedback game (FG). Thirty of the 50 children were randomized to undergo extensive off-scanner training with the FG using a MRI simulator, or no off-scanner training. Navigator efficiency, signal-to-noise ratio (SNR), and global left-ventricular strains were determined for each participant and compared. RESULTS: Using the FG improved average navigator efficiency from 33 ± 15 to 58 ± 13 % (p < 0.001) and improved SNR by 5 % (p = 0.01) compared to acquisitions with NF. There was no difference in navigator efficiency (p = 0.90) or SNR (p = 0.77) between untrained and trained participants for FG acquisitions. Circumferential and radial strains derived from FG acquisitions were slightly reduced compared to NF acquisitions (-16 ± 2 % vs -17 ± 2 %, p < 0.001; 40 ± 10 % vs 44 ± 11 %, p = 0.005, respectively). There were no differences in longitudinal strain (p = 0.38). CONCLUSIONS: Use of a respiratory navigator feedback game during navigator-gated CMR improved navigator efficiency in children from 33 to 58 %. This improved efficiency was associated with a 5 % increase in SNR for spiral cine DENSE. Extensive off-scanner training was not required to achieve the improvement in navigator efficiency.

Gadolinium free cardiovascular magnetic resonance with 2-point Cine balanced steady state free precession.

BACKGROUND: Cardiovascular magnetic resonance (CMR) of ventricular structure and function is widely performed using cine balanced steady state free precession (bSSFP) MRI. The bSSFP signal of myocardium is weighted by magnetization transfer (MT) and T1/T2-relaxation times. In edematous and fibrotic tissues, increased T2 and reduced MT lead to increased signal intensity on images acquired with high excitation flip angles. We hypothesized that acquisition of two differentially MT-weighted bSSFP images (termed 2-point bSSFP) can identify tissue that would enhance with gadolinium similar to standard of care late gadolinium enhancement (LGE). METHODS: Cine bSSFP images (flip angles of 5° and 45°) and native-T1 and T2 maps were acquired in one mid-ventricular slice in 47 patients referred for CMR and 10 healthy controls. Afterwards, LGE images and post-contrast T1 maps were acquired and gadolinium partition coefficient (GPC) was calculated. Maps of ΔS/So were calculated as (S45-S5)/S5*100 (%), where Sflip_angle is the voxel signal intensity. RESULTS: Twenty three patients demonstrated areas of myocardial hyper-enhancement with LGE. In enhanced regions, ΔS/So, native-T1, T2, and GPC were heightened (p < 0.05 vs. non-enhanced tissues). ΔS/So, native-T1, and T2 all demonstrated association with GPC, however the association was strongest for ΔS/So. Bland-Altman analysis revealed a slight bias towards larger volume of enhancement with ΔS/So compared to LGE, and similar transmurality. Subjective analysis with 2-blinded expert readers revealed agreement between ΔS/So and LGE of 73.4 %, with false positive detection of 16.7 % and false negative detection of 15.2 %. CONCLUSIONS: Gadolinium free 2-point bSSFP identified tissue that enhances at LGE with strong association to GPC. Our results suggest that with further development, MT-weighted CMR could be used similar to LGE for diagnostic imaging.

A cortical locus for anisotropic overlay suppression of stimuli presented at fixation.

Human contrast sensitivity for narrowband Gabor targets is suppressed when superimposed on narrowband masks of the same spatial frequency and orientation (referred to as overlay suppression), with suppression being broadly tuned to orientation and spatial frequency. Numerous behavioral and neurophysiological experiments have suggested that overlay suppression originates from the initial lateral geniculate nucleus (LGN) inputs to V1, which is consistent with the broad tuning typically reported for overlay suppression. However, recent reports have shown narrowly tuned anisotropic overlay suppression when narrowband targets are masked by broadband noise. Consequently, researchers have argued for an additional form of overlay suppression that involves cortical contrast gain control processes. The current study sought to further explore this notion behaviorally using narrowband and broadband masks, along with a computational neural simulation of the hypothesized underlying gain control processes in cortex. Additionally, we employed transcranial direct current stimulation (tDCS) in order to test whether cortical processes are involved in driving narrowly tuned anisotropic suppression. The behavioral results yielded anisotropic overlay suppression for both broadband and narrowband masks and could be replicated with our computational neural simulation of anisotropic gain control. Further, the anisotropic form of overlay suppression could be directly modulated by tDCS, which would not be expected if the suppression was primarily subcortical in origin. Altogether, the results of the current study provide further evidence in support of an additional overlay suppression process that originates in cortex and show that this form of suppression is also observable with narrowband masks.