Brandon K. Fornwalt

Validation of in vivo 2D Displacements from Spiral Cine DENSE at 3T

BackgroundDisplacement Encoding with Stimulated Echoes (DENSE) encodes displacement into the phase of the magnetic resonance signal. Due to the stimulated echo, the signal is inherently low and fades through the cardiac cycle. To compensate, a spiral acquisition has been used at 1.5T. This spiral sequence has not been validated at 3T, where the increased signal would be valuable, but field inhomogeneities may result in measurement errors. We hypothesized that spiral cine DENSE is valid at 3T and tested this hypothesis by measuring displacement errors at both 1.5T and 3T in vivo.MethodsTwo-dimensional spiral cine DENSE and tagged imaging of the left ventricle were performed on ten healthy subjects at 3T and six healthy subjects at 1.5T. Intersection points were identified on tagged images near end-systole. Displacements from the DENSE images were used to project those points back to their origins. The deviation from a perfect grid was used as a measure of accuracy and quantified as root-mean-squared error. This measure was compared between 3T and 1.5T with the Wilcoxon rank sum test. Inter-observer variability of strains and torsion quantified by DENSE and agreement between DENSE and harmonic phase (HARP) were assessed by Bland-Altman analyses. The signal to noise ratio (SNR) at each cardiac phase was compared between 3T and 1.5T with the Wilcoxon rank sum test.ResultsThe displacement accuracy of spiral cine DENSE was not different between 3T and 1.5T (1.2u2009±u20090.3 mm and 1.2u2009±u20090.4 mm, respectively). Both values were lower than the DENSE pixel spacing of 2.8 mm. There were no substantial differences in inter-observer variability of DENSE or agreement of DENSE and HARP between 3T and 1.5T. Relative to 1.5T, the SNR at 3T was greater by a factor of 1.4u2009±u20090.3.ConclusionsThe spiral cine DENSE acquisition that has been used at 1.5T to measure cardiac displacements can be applied at 3T with equivalent accuracy. The inter-observer variability and agreement of DENSE-derived peak strains and torsion with HARP is also comparable at both field strengths. Future studies with spiral cine DENSE may take advantage of the additional SNR at 3T.

Advanced cardiac chemical exchange saturation transfer (cardioCEST) MRI for in vivo cell tracking and metabolic imaging.

An improved pre‐clinical cardiac chemical exchange saturation transfer (CEST) pulse sequence (cardioCEST) was used to selectively visualize paramagnetic CEST (paraCEST)‐labeled cells following intramyocardial implantation. In addition, cardioCEST was used to examine the effect of diet‐induced obesity upon myocardial creatine CEST contrast. CEST pulse sequences were designed from standard turbo‐spin‐echo and gradient‐echo sequences, and a cardiorespiratory‐gated steady‐state cine gradient‐echo sequence. In vitro validation studies performed in phantoms composed of 20u2009mM Eu‐HPDO3A, 20u2009mM Yb‐HPDO3A, or saline demonstrated similar CEST contrast by spin‐echo and gradient‐echo pulse sequences. Skeletal myoblast cells (C2C12) were labeled with either Eu‐HPDO3A or saline using a hypotonic swelling procedure and implanted into the myocardium of C57B6/J mice. Inductively coupled plasma mass spectrometry confirmed cellular levels of Eu of 2.1u2009×u200910−3 ng/cell in Eu‐HPDO3A‐labeled cells and 2.3u2009×u200910−5 ng/cell in saline‐labeled cells. In vivo cardioCEST imaging of labeled cells at ±15u2009ppm was performed 24u2009h after implantation and revealed significantly elevated asymmetric magnetization transfer ratio values in regions of Eu‐HPDO3A‐labeled cells when compared with surrounding myocardium or saline‐labeled cells. We further utilized the cardioCEST pulse sequence to examine changes in myocardial creatine in response to diet‐induced obesity by acquiring pairs of cardioCEST images at ±1.8u2009ppm. While ventricular geometry and function were unchanged between mice fed either a high‐fat diet or a corresponding control low‐fat diet for 14u2009weeks, myocardial creatine CEST contrast was significantly reduced in mice fed the high‐fat diet. The selective visualization of paraCEST‐labeled cells using cardioCEST imaging can enable investigation of cell fate processes in cardioregenerative medicine, or multiplex imaging of cell survival with imaging of cardiac structure and function and additional imaging of myocardial creatine. Copyright

Cardiac remodeling and dysfunction in childhood obesity: a cardiovascular magnetic resonance study

BackgroundObesity affects nearly one in five children and is associated with increased risk of premature death. Obesity-related heart disease contributes to premature death. We aimed to use cardiovascular magnetic resonance (CMR) to comprehensively characterize the changes in cardiac geometry and function in obese children.Methods and resultsForty-one obese/overweight (age 12u2009±u20093xa0years, 56xa0% female) and 29 healthy weight children (age 14u2009±u20093xa0years, 41xa0% female) underwent CMR, including both standard cine imaging and displacement encoded imaging, for a complete assessment of left ventricular (LV) structure and function. After adjusting for age, LV mass index was 23xa0% greater (27u2009±u20094xa0g/m2.7 vs 22u2009±u20093xa0g/m2.7, p <0.001) and the LV myocardium was 10xa0% thicker (5.6u2009±u20090.8xa0mm vs 5.1u2009±u20090.8xa0mm, p <0.001) in the obese/overweight children. This evidence of cardiac remodeling was present in obese children as young as age 8. Twenty four percent of obese/overweight children had concentric hypertrophy, 59xa0% had normal geometry and 17xa0% had either eccentric hypertrophy or concentric remodeling. LV mass index, thickness, ejection fraction and peak longitudinal and circumferential strains all correlated with epicardial adipose tissue after adjusting for height and gender (all p <0.05). Peak longitudinal and circumferential strains showed a significant relationship with the type of LV remodeling, and were most impaired in children with concentric hypertrophy (p <0.001 and pu2009=u20090.003, respectively).ConclusionsObese children show evidence of significant cardiac remodeling and dysfunction, which begins as young as age 8. Obese children with concentric hypertrophy and impaired strain may represent a particularly high risk subgroup that demands further investigation.

Left and right ventricular dyssynchrony and strains from cardiovascular magnetic resonance feature tracking do not predict deterioration of ventricular function in patients with repaired tetralogy of Fallot

BackgroundPatients with repaired tetralogy of Fallot (rTOF) suffer from progressive ventricular dysfunction decades after their surgical repair. We hypothesized that measures of ventricular strain and dyssynchrony would predict deterioration of ventricular function in patients with rTOF.MethodsA database search identified all patients at a single institution with rTOF who underwent cardiovascular magnetic resonance (CMR) at least twice, >6 months apart, without intervening surgical or catheter procedures. Seven primary predictors were derived from the first CMR using a custom feature tracking algorithm: left (LV), right (RV) and inter-ventricular dyssynchrony, LV and RV peak global circumferential strains, and LV and RV peak global longitudinal strains. Three outcomes were defined, whose changes were assessed over time: RV end-diastolic volume, and RV and LV ejection fraction. Multivariate linear mixed models were fit to investigate relationships of outcomes to predictors and ten potential baseline confounders.ResultsOne hundred fifty-three patients with rTOF (23 ± 14 years, 50 % male) were included. The mean follow-up duration between the first and last CMR was 2.9 ± 1.3 years. After adjustment for confounders, none of the 7 primary predictors were significantly associated with change over time in the 3 outcome variables. Only 1–17 % of the variability in the change over time in the outcome variables was explained by the baseline predictors and potential confounders.ConclusionsIn patients with repaired tetralogy of Fallot, ventricular dyssynchrony and global strain derived from cine CMR were not significantly related to changes in ventricular size and function over time. The ability to predict deterioration in ventricular function in patients with rTOF using current methods is limited.

Electronic health record phenotype in subjects with genetic variants associated with arrhythmogenic right ventricular cardiomyopathy: a study of 30,716 subjects with exome sequencing

PurposeArrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart disease. Clinical follow-up of incidental findings in ARVC-associated genes is recommended. We aimed to determine the prevalence of disease thus ascertained.MethodsIndividuals (nxa0=xa030,716) underwent exome sequencing. Variants in PKP2, DSG2, DSC2, DSP, JUP, TMEM43, or TGFβ3 that were database-listed as pathogenic or likely pathogenic were identified and evidence-reviewed. For subjects with putative loss-of-function (pLOF) variants or variants of uncertain significance (VUS), electronic health records (EHR) were reviewed for ARVC diagnosis, diagnostic criteria, and International Classification of Diseases (ICD-9) codes.ResultsEighteen subjects had pLOF variants; none of these had an EHR diagnosis of ARVC. Of 14 patients with an electrocardiogram, one had a minor diagnostic criterion; the rest were normal. A total of 184 subjects had VUS, none of whom had an ARVC diagnosis. The proportion of subjects with VUS with major (4%) or minor (13%) electrocardiogram diagnostic criteria did not differ from that of variant-negative controls. ICD-9 codes showed no difference in defibrillator use, electrophysiologic abnormalities or nonischemic cardiomyopathies in patients with pLOF or VUSs compared with controls.ConclusionpLOF variants in an unselected cohort were not associated with ARVC phenotypes based on EHR review. The negative predictive value of EHR review remains uncertain.

Simplified post processing of cine DENSE cardiovascular magnetic resonance for quantification of cardiac mechanics

BackgroundCardiovascular magnetic resonance using displacement encoding with stimulated echoes (DENSE) is capable of assessing advanced measures of cardiac mechanics such as strain and torsion. A potential hurdle to widespread clinical adoption of DENSE is the time required to manually segment the myocardium during post-processing of the images. To overcome this hurdle, we proposed a radical approach in which only three contours per image slice are required for post-processing (instead of the typical 30–40 contours per image slice). We hypothesized that peak left ventricular circumferential, longitudinal and radial strains and torsion could be accurately quantified using this simplified analysis.Methods and ResultsWe tested our hypothesis on a large multi-institutional dataset consisting of 541 DENSE image slices from 135 mice and 234 DENSE image slices from 62 humans. We compared measures of cardiac mechanics derived from the simplified post-processing to those derived from original post-processing utilizing the full set of 30–40 manually-defined contours per image slice. Accuracy was assessed with Bland-Altman limits of agreement and summarized with a modified coefficient of variation. The simplified technique showed high accuracy with all coefficients of variation less than 10% in humans and 6% in mice. The accuracy of the simplified technique was also superior to two previously published semi-automated analysis techniques for DENSE post-processing.ConclusionsAccurate measures of cardiac mechanics can be derived from DENSE cardiac magnetic resonance in both humans and mice using a simplified technique to reduce post-processing time by approximately 94%. These findings demonstrate that quantifying cardiac mechanics from DENSE data is simple enough to be integrated into the clinical workflow.

2D cine DENSE with low encoding frequencies accurately quantifies cardiac mechanics with improved image characteristics.

BackgroundDisplacement Encoding with Stimulated Echoes (DENSE) encodes displacement into the phase of the magnetic resonance signal. The encoding frequency (ke) maps the measured phase to tissue displacement while the strength of the encoding gradients affects image quality. 2D cine DENSE studies have used a ke of 0.10xa0cycles/mm, which is high enough to remove an artifact-generating echo from k-space, provide high sensitivity to tissue displacements, and dephase the blood pool. However, through-plane dephasing can remove the unwanted echo and dephase the blood pool without relying on high ke. Additionally, the high sensitivity comes with the costs of increased phase wrapping and intra-voxel dephasing. We hypothesized that ke below 0.10xa0cycles/mm can be used to improve image characteristics and provide accurate measures of cardiac mechanics.MethodsSpiral cine DENSE images were obtained for 10 healthy subjects and 10 patients with a history of heart disease on a 3xa0T Siemens Trio. A mid-ventricular short-axis image was acquired with different ke: 0.02, 0.04, 0.06, 0.08, and 0.10xa0cycles/mm. Peak twist, circumferential strain, and radial strain were compared between acquisitions employing different ke using Bland-Altman analyses and coefficients of variation. The percentage of wrapped pixels in the phase images at end-systole was calculated for each ke. The dephasing of the blood signal and signal to noise ratio (SNR) were also calculated and compared.ResultsNegligible differences were seen in strains and twist for all ke between 0.04 and 0.10xa0cycles/mm. These differences were of the same magnitude as inter-test differences. Specifically, the acquisitions with 0.04xa0cycles/mm accurately quantified cardiac mechanics and had zero phase wrapping. Compared to 0.10xa0cycles/mm, the acquisitions with 0.04xa0cycles/mm had 9xa0% greater SNR and negligible differences in blood pool dephasing.ConclusionsFor 2D cine DENSE with through-plane dephasing, the encoding frequency can be lowered to 0.04xa0cycles/mm without compromising the quantification of twist or strain. The amount of wrapping can be reduced with this lower value to greatly simplify the input to unwrapping algorithms. The strain and twist results from studies using different encoding frequencies can be directly compared.

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.

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

BackgroundAdvanced 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.MethodsWe 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 (±3xa0mm) throughout image acquisition.Using a 3T Siemens Tim Trio, 50 children (Age: 14u2009±u20093xa0years, 48xa0% 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.ResultsUsing the FG improved average navigator efficiency from 33u2009±u200915 to 58u2009±u200913xa0% (pu2009<u20090.001) and improved SNR by 5xa0% (pu2009=u20090.01) compared to acquisitions with NF. There was no difference in navigator efficiency (pu2009=u20090.90) or SNR (pu2009=u20090.77) between untrained and trained participants for FG acquisitions. Circumferential and radial strains derived from FG acquisitions were slightly reduced compared to NF acquisitions (−16u2009±u20092xa0% vs −17u2009±u20092xa0%, pu2009<u20090.001; 40u2009±u200910xa0% vs 44u2009±u200911xa0%, pu2009=u20090.005, respectively). There were no differences in longitudinal strain (pu2009=u20090.38).ConclusionsUse of a respiratory navigator feedback game during navigator-gated CMR improved navigator efficiency in children from 33 to 58xa0%. This improved efficiency was associated with a 5xa0% increase in SNR for spiral cine DENSE. Extensive off-scanner training was not required to achieve the improvement in navigator efficiency.

Regional quantification of myocardial mechanics in rat using 3D cine DENSE cardiovascular magnetic resonance.

Rat models have assumed an increasingly important role in cardiac research. However, a detailed profile of regional cardiac mechanics, such as strains and torsion, is lacking for rats. We hypothesized that healthy rat left ventricles (LVs) exhibit regional differences in cardiac mechanics, which are part of normal function. In this study, images of the LV were obtained with 3D cine displacement encoding with stimulated echoes (DENSE) cardiovascular magnetic resonance in 10 healthy rats. To evaluate regional cardiac mechanics, the LV was divided into basal, mid‐ventricular, and apical regions. The myocardium at the mid‐LV was further partitioned into four wall segments (i.e. septal, inferior, lateral, and anterior) and three transmural layers (i.e. sub‐endocardium, mid‐myocardium, and sub‐epicardium). The six Lagrangian strain components (i.e. Err, Ecc, Ell, Ecl, Erl, and Ecr) were computed from the 3D displacement field and averaged within each region of interest. Torsion was quantified using the circumferential‐longitudinal shear angle. While peak systolic Ecl differed between the mid‐ventricle and apex, the other five components of peak systolic strain were similar across the base, mid‐ventricle, and apex. In the mid‐LV myocardium, Ecc decreased gradually from the sub‐endocardial to the sub‐epicardial layer. Ell demonstrated significant differences between the four wall segments, with the largest magnitude in the inferior segment. Err was uniform among the four wall segments. Ecl varied along the transmural direction and among wall segments, whereas Erl differed only among the wall segments. Erc was not associated with significant variations. Torsion also varied along the transmural direction and among wall segments. These results provide fundamental insights into the regional contractile function of healthy rat hearts, and form the foundation for future studies on regional changes induced by disease or treatments.