Clinical correlates of CT imaging-derived phenotypes among lean and overweight patients with hepatic steatosis.

The objective of this study is to define CT imaging derived phenotypes for patients with hepatic steatosis, a common metabolic liver condition, and determine its association with patient data from a medical biobank. There is a need to further characterize hepatic steatosis in lean patients, as its epidemiology may differ from that in overweight patients. A deep learning method determined the spleen-hepatic attenuation difference (SHAD) in Hounsfield Units (HU) on abdominal CT scans as a quantitative measure of hepatic steatosis. The patient cohort was stratified by BMI with a threshold of 25 kg/m2 and hepatic steatosis with threshold SHAD ≥ - 1 HU or liver mean attenuation ≤ 40 HU. Patient characteristics, diagnoses, and laboratory results representing metabolism and liver function were investigated. A phenome-wide association study (PheWAS) was performed for the statistical interaction between SHAD and the binary characteristic LEAN. The cohort contained 8914 patients-lean patients with (N = 278, 3.1%) and without (N = 1867, 20.9%) steatosis, and overweight patients with (N = 1863, 20.9%) and without (N = 4906, 55.0%) steatosis. Among all lean patients, those with steatosis had increased rates of cardiovascular disease (41.7 vs 27.8%), hypertension (86.7 vs 49.8%), and type 2 diabetes mellitus (29.1 vs 15.7%) (all p < 0.0001). Ten phenotypes were significant in the PheWAS, including chronic kidney disease, renal failure, and cardiovascular disease. Hepatic steatosis was found to be associated with cardiovascular, kidney, and metabolic conditions, separate from overweight BMI.

Magnetic resonance myocardial T1ρ mapping : Technical overview, challenges, emerging developments, and clinical applications.

The potential of cardiac magnetic resonance to improve cardiovascular care and patient management is considerable. Myocardial T1-rho (T1ρ) mapping, in particular, has emerged as a promising biomarker for quantifying myocardial injuries without exogenous contrast agents. Its potential as a contrast-agent-free ("needle-free") and cost-effective diagnostic marker promises high impact both in terms of clinical outcomes and patient comfort. However, myocardial T1ρ mapping is still at a nascent stage of development and the evidence supporting its diagnostic performance and clinical effectiveness is scant, though likely to change with technological improvements. The present review aims at providing a primer on the essentials of myocardial T1ρ mapping, and to describe the current range of clinical applications of the technique to detect and quantify myocardial injuries. We also delineate the important limitations and challenges for clinical deployment, including the urgent need for standardization, the evaluation of bias, and the critical importance of clinical testing. We conclude by outlining technical developments to be expected in the future. If needle-free myocardial T1ρ mapping is shown to improve patient diagnosis and prognosis, and can be effectively integrated in cardiovascular practice, it will fulfill its potential as an essential component of a cardiac magnetic resonance examination.

Cardiovascular Magnetic Resonance in Early Detection of Radiation Associated Cardiotoxicity With Chest Radiation.

Background: Chest radiation therapy (RT) is known to be associated with cardiotoxicity. However, the changes in myocardial tissue characterization with radiation-induced cardiotoxicity are not well-understood. Objectives: This study sought to assess the changes in left ventricular function and tissue characterization using cardiovascular magnetic resonance (CMR) in patients receiving RT. Materials and Methods: Between June 2015 and July 2018, we enrolled patients with breast, lung cancer, or lymphoma with plan to receive chest radiation after chemotherapy. CMR was performed using a 1.5T scanner at baseline and 6 months after RT. Myocardial volume, function, strain analysis using feature tracking, and tissue characterization including late gadolinium enhancement (LGE), T1, T2, T1ρ (rho), and extracellular volume fraction (ECV) were measured and compared using non-parametric methods. Results: The final cohort consisted of 16 patients, 11 of whom completed both baseline and follow-up CMRs. Patients were matched to 10 healthy controls. At baseline prior to RT, compared to controls, patients had lower global circumferential strain (GCS) (15.3 ± 2.2% vs.18.4 ± 2.1%, p = 0.004), and elevated T2 (47.9 ± 4.8 ms vs. 45.0 ± 1.5 ms, p = 0.04) and T1ρ values (78.4 ± 5.9 vs. 66.9 ± 4.6 ms, p < 0.001). Two patients had LGE. There was no significant difference in the average T1 values or ECV. There was a trend toward lower LV ejection fraction and global longitudinal strain (GLS). At 6-month follow-up after RT, there were no significant changes in all the CMR parameters. Conclusion: At 6-month following chest radiation therapy, there was no change in LV and RV EF, LV and RV GLS, LV GCS, and myocardial tissue characterization using LGE, T1, ECV, T2, and T1ρ in a small cohort of patients. However, the baseline T2 and T1ρ were elevated and LV GCS was reduced compared to controls indicating ongoing myocardial edema and subclinical dysfunction post-chemotherapy.

Endogenous T1ρ cardiovascular magnetic resonance in hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is characterized by increased left ventricular wall thickness, cardiomyocyte hypertrophy, and fibrosis. Adverse cardiac risk characterization has been performed using late gadolinium enhancement (LGE), native T1, and extracellular volume (ECV). Relaxation time constants are affected by background field inhomogeneity. T1ρ utilizes a spin-lock pulse to decrease the effect of unwanted relaxation. The objective of this study was to study T1ρ as compared to T1, ECV, and LGE in HCM patients. METHODS: HCM patients were recruited as part of the Novel Markers of Prognosis in Hypertrophic Cardiomyopathy study, and healthy controls were matched for comparison. In addition to cardiac functional imaging, subjects underwent T1 and T1ρ cardiovascular magnetic resonance imaging at short-axis positions at 1.5T. Subjects received gadolinium and underwent LGE imaging 15-20 min after injection covering the entire heart. Corresponding basal and mid short axis LGE slices were selected for comparison with T1 and T1ρ. Full-width half-maximum thresholding was used to determine the percent enhancement area in each LGE-positive slice by LGE, T1, and T1ρ. Two clinicians independently reviewed LGE images for presence or absence of enhancement. If in agreement, the image was labeled positive (LGE + +) or negative (LGE --); otherwise, the image was labeled equivocal (LGE + -). RESULTS: In 40 HCM patients and 10 controls, T1 percent enhancement area (Spearman's rho = 0.61, p < 1e-5) and T1ρ percent enhancement area (Spearman's rho = 0.48, p < 0.001e-3) correlated with LGE percent enhancement area. T1 and T1ρ percent enhancement areas were also correlated (Spearman's rho = 0.28, p = 0.047). For both T1 and T1ρ, HCM patients demonstrated significantly longer relaxation times compared to controls in each LGE category (p < 0.001 for all). HCM patients also showed significantly higher ECV compared to controls in each LGE category (p < 0.01 for all), and LGE -- slices had lower ECV than LGE + + (p = 0.01). CONCLUSIONS: Hyperenhancement areas as measured by T1ρ and LGE are moderately correlated. T1, T1ρ, and ECV were elevated in HCM patients compared to controls, irrespective of the presence of LGE. These findings warrant additional studies to investigate the prognostic utility of T1ρ imaging in the evaluation of HCM patients.

Closed-loop control of k-space sampling via physiologic feedback for cine MRI.

BACKGROUND: Segmented cine cardiac MRI combines data from multiple heartbeats to achieve high spatiotemporal resolution cardiac images, yet predefined k-space segmentation trajectories can lead to suboptimal k-space sampling. In this work, we developed and evaluated an autonomous and closed-loop control system for radial k-space sampling (ARKS) to increase sampling uniformity. METHODS: The closed-loop system autonomously selects radial k-space sampling trajectory during live segmented cine MRI and attempts to optimize angular sampling uniformity by selecting views in regions of k-space that were not previously well-sampled. Sampling uniformity and the ability to detect cardiac phase in vivo was assessed using ECG data acquired from 10 normal subjects in an MRI scanner. The approach was then implemented with a fast gradient echo sequence on a whole-body clinical MRI scanner and imaging was performed in 4 healthy volunteers. The closed-loop k-space trajectory was compared to random, uniformly distributed and golden angle view trajectories via measurement of k-space uniformity and the point spread function. Lastly, an arrhythmic dataset was used to evaluate a potential application of the approach. RESULTS: The autonomous trajectory increased k-space sampling uniformity by 15±7%, main lobe point spread function (PSF) signal intensity by 6±4%, and reduced ringing relative to golden angle sampling. When implemented, the autonomous pulse sequence prescribed radial view angles faster than the scan TR (0.98 ± 0.01 ms, maximum = 1.38 ms) and increased k-space sampling mean uniformity by 10±11%, decreased uniformity variability by 44±12%, and increased PSF signal ratio by 6±6% relative to golden angle sampling. CONCLUSION: The closed-loop approach enables near-uniform radial sampling in a segmented acquisition approach which was higher than predetermined golden-angle radial sampling. This can be utilized to increase the sampling or decrease the temporal footprint of an acquisition and the closed-loop framework has the potential to be applied to patients with complex heart rhythms.

Assessment of uterine artery geometry and hemodynamics in human pregnancy with 4d flow mri and its correlation with doppler ultrasound.

BACKGROUND: Uterine artery (UtA) hemodynamics might be used to predict risk of hypertensive pregnancy disorders, including preeclampsia and intrauterine growth restriction. PURPOSE OR HYPOTHESIS: To determine the feasibility of 4D flow MRI in pregnant subjects by characterizing UtA anatomy, computing UtA flow, and comparing UtA velocity, and pulsatility and resistivity indices (PI, RI) with transabdominal Doppler ultrasound (US). STUDY TYPE: Prospective cross-sectional study from June 6, 2016, to May 2, 2018. POPULATION OR SUBJECTS OR PHANTOM OR SPECIMEN OR ANIMAL MODEL: Forty-one singleton pregnant subjects (age [range] = 27.0 ± 5.9 [18-41] years) in their second or third trimester. We additionally scanned three subjects who had prepregnancy diabetes or chronic hypertension. FIELD STRENGTH/SEQUENCE: The subjects underwent UtA and placenta MRI using noncontrast angiography and 4D flow at 1.5T. ASSESSMENT: UtA anatomy was described based on 4D flow-derived noncontrast angiography, while UtA flow properties were characterized by net flow, systolic/mean/diastolic velocity, PI and RI through examination of 4D flow data. PI and RI are standard hemodynamic parameters routinely reported on Doppler US. STATISTICAL TESTS: Spearman's rank correlation, Wilcoxon signed rank tests, and Bland-Altman plots were used to preliminarily investigate the relationships between flow parameters, gestational age, and Doppler US. or RESULTS: 4D flow MRI and UtA flow quantification was feasible in all subjects. There was considerable heterogeneity in UtA geometry in each subject between left and right UtAs and between subjects. Mean 4D flow-based parameters were: mean bilateral flow rate = 605.6 ± 220.5 mL/min, PI = 0.72 ± 0.2, and RI = 0.47 ± 0.1. Bilateral flow did not change with gestational age. We found that MRI differed from US in terms of lower PI (mean difference -0.1) and RI (mean difference < -0.1) with Wilcoxon signed rank test P = 0.05 and P = 0.13, respectively. DATA CONCLUSION: 4D flow MRI is a feasible approach for describing UtA anatomy and flow in pregnant subjects. LEVEL OF EVIDENCE: Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:59-68.

An all-in-one nanoparticle (AION) contrast agent for breast cancer screening with DEM-CT-MRI-NIRF imaging.

Conventional X-ray mammography has low diagnostic sensitivity for women with dense breasts. As a result, alternative contrast-enhanced screening tools such as dual energy mammography (DEM), computed tomography (CT), magnetic resonance imaging (MRI), and near-infrared fluorescence (NIRF) imaging are being used or investigated for these women. However, currently available contrast agents are non-ideal, have safety issues, and each imaging technique requires a different contrast agent. We therefore sought to develop a multimodal contrast agent that is functional for each breast imaging modality to simplify the diagnosis process and address the issues of existing contrast agents. Herein, we present a novel "all-in-one" nanoparticle (AION) multimodal imaging probe that has potent DEM, CT, MRI, and NIRF contrast properties and improved biocompatibility. AION were formed by co-encapsulation of a near-infrared fluorophore (DiR), silver sulfide nanoparticles (Ag2S-NP), and iron oxide nanoparticles (IO-NP) in PEGylated micelles. AION showed negligible cytotoxicity, which was in agreement with its minimal silver ion release profiles. AION generated strong contrast with all imaging modalities as demonstrated in phantom imaging. AION allowed in vivo tumor imaging as evidenced by the increase in contrast after injection. This study indicates the potential of AION as an effective multimodal contrast agent for breast cancer diagnosis with a range of imaging methods.

Native T1 and T2 mapping by cardiovascular magnetic resonance imaging in pressure overloaded left and right heart diseases.

BACKGROUND: Pulmonary arterial hypertension (PAH) and severe aortic valve stenosis (AS) are diseases characterized by increased afterload of the right and left heart, respectively. Our study aims to investigate the differences of myocardial tissue characteristics in the pressure overloaded left and right hearts, especially in the shared interventricular septum, as detected by native T1 and T2 relaxation times. METHODS: Eighteen patients with PAH and 19 patients with severe AS in addition to 5 healthy volunteers underwent 1.5-T CMR examination with native T1 and T2 mapping. Mean T1 and T2 value were measured at the right ventricular (RV) free wall, superior RV insertion, inferior RV insertion, interventricular septum and left ventricular (LV) lateral wall. RESULTS: Compared with controls and AS group, T1 was significantly elevated in the RV insertion in PAH group (P=0.015), while no statistically significant differences were seen in other segments among the three groups. There was an increase of T2 in the RV insertion in AS and PAH groups (P=0.01). Significant T2 elevation was also observed in the RV free wall of PAH group, and the LV lateral wall of AS group compared with the control group. RV insertion T2 was significantly correlated with RV end-diastolic volume index (r=0.608, P=0.016) and RV mass index (r=0.57, P=0.026) in the PAH group. LV lateral wall T2 and RV insertion T2 were significantly correlated with aortic valve mean gradients in the AS group (r=0.56, P=0.02; r=0.58, P=0.01, respectively). CONCLUSIONS: In pressure overload diseases, both T1 and T2 values increase in the myocardium. The alterations seen in the RV insertion sites in the septum was more pronounced with RV pressure overload. T2 values also correlated with structural and functional remodeling in both diseases. Combining T1 and T2 mapping may help to better characterize the alternation of myocardial composition in pressure overloaded heart diseases.

Assessment of myocardial injury after reperfused infarction by T1ρ cardiovascular magnetic resonance.

BACKGROUND: The evolution of T1ρ and of other endogenous contrast methods (T2, T1) in the first month after reperfused myocardial infarction (MI) is uncertain. We conducted a study of reperfused MI in pigs to serially monitor T1ρ, T2 and T1 relaxation, scar size and transmurality at 1 and 4 weeks post-MI. METHODS: Ten Yorkshire swine underwent 90 min of occlusion of the circumflex artery and reperfusion. T1ρ, T2 and native T1 maps and late gadolinium enhanced (LGE) cardiovascular magnetic resonance (CMR) data were collected at 1 week (n = 10) and 4 weeks (n = 5). Semi-automatic FWHM (full width half maximum) thresholding was used to assess scar size and transmurality and compared to histology. Relaxation times and contrast-to-noise ratio were compared in healthy and remote myocardium at 1 and 4 weeks. Linear regression and Bland-Altman was performed to compare infarct size and transmurality. RESULTS: Relaxation time differences between infarcted and remote myocardial tissue were ∆T1 (infarct-remote) = 421.3 ± 108.8 (1 week) and 480.0 ± 33.2 ms (4 week), ∆T1ρ = 68.1 ± 11.6 and 74.3 ± 14.2, and ∆T2 = 51.0 ± 10.1 and 59.2 ± 11.4 ms. Contrast-to-noise ratio was CNRT1 = 7.0 ± 3.5 (1 week) and 6.9 ± 2.4 (4 week), CNRT1ρ = 12.0 ± 6.2 and 12.3 ± 3.2, and CNRT2 = 8.0 ± 3.6 and 10.3 ± 5.8. Infarct size was not significantly different for T1ρ, T1 and T2 compared to LGE (p = 0.14) and significantly decreased from 1 to 4 weeks (p < 0.01). Individual infarct size changes were ∆T1ρ = -3.8%, ∆T1 = -3.5% and ∆LGE = -2.8% from 1 - 4 weeks, but there was no observed change in infarct size for T2 or histologically. CONCLUSIONS: T1ρ was highly correlated with alterations left ventricle (LV) pathology at 1 and 4 weeks post-MI and therefore it may be a useful method endogenous contrast imaging of infarction.

Spatial phenotyping of the endocardial endothelium as a function of intracardiac hemodynamic shear stress.

Despite substantial evidence for the central role of hemodynamic shear stress in the functional integrity of vascular endothelial cells, hemodynamic and molecular regulation of the endocardial endothelium lining the heart chambers remains understudied. We propose that regional differences in intracardiac hemodynamics influence differential endocardial gene expression leading to phenotypic heterogeneity of this cell layer. Measurement of intracardiac hemodynamics was performed using 4-dimensional flow MRI in healthy humans (n=8) and pigs (n=5). Local wall shear stress (WSS) and oscillatory shear indices (OSI) were calculated in three distinct regions of the LV - base, mid-ventricle (midV), and apex. In both the humans and pigs, WSS values were significantly lower in the apex and midV relative to the base. Additionally, both the apex and midV had greater oscillatory shear indices (OSI) than the base. To investigate regional phenotype, endocardial endothelial cells (EEC) were isolated from an additional 8 pigs and RNA sequencing was performed. A false discovery rate of 0.10 identified 1051 differentially expressed genes between the base and apex, and 321 between base and midV. Pathway analyses revealed apical upregulation of genes associated with translation initiation. Furthermore, tissue factor pathway inhibitor (TFPI; mean 50-fold) and prostacyclin synthase (PTGIS; 5-fold), genes prominently associated with antithrombotic protection, were consistently upregulated in LV apex. These spatio-temporal WSS values in defined regions of the left ventricle link local hemodynamics to regional heterogeneity in endocardial gene expression.

Self-gated MRI of multiple beat morphologies in the presence of arrhythmias.

PURPOSE: Develop self-gated MRI for distinct heartbeat morphologies in subjects with arrhythmias. METHODS: Golden angle radial data was obtained in seven sinus and eight arrhythmias subjects. An image-based cardiac navigator was derived from single-shot images, distinct beat types were identified, and images were reconstructed for repeated morphologies. Image sharpness, contrast, and volume variation were quantified and compared with self-gated MRI. Images were scored for image quality and artifacts. Hemodynamic parameters were computed for each distinct beat morphology in bigeminy and trigeminy subjects and for sinus beats in patients with infrequent premature ventricular contractions. RESULTS: Images of distinct beat types were reconstructed except for two patients with infrequent premature ventricular contractions. Image contrast and sharpness were similar to sinus self-gated images (contrast = 0.45 ± 0.13 and 0.43 ± 0.15; sharpness = 0.21 ± 0.11 and 0.20 ± 0.05). Visual scoring was highest in self-gated images (4.1 ± 0.3) compared with real-time (3.9 ± 0.4) and ECG-gated cine (3.4 ± 1.5). ECG-gated cine had less artifacts than self-gating (2.3 ± 0.7 and 2.1 ± 0.2), but was affected by misgating in two subjects. Among arrhythmia subjects, post-extrasystole/sinus (58.1 ± 8.6 mL) and interrupted sinus (61.4 ± 5.9 mL) stroke volume was higher than extrasystole (32.0 ± 16.5 mL; P < 0.02). CONCLUSION: Self-gated imaging can reconstruct images during ectopy and allowed for quantification of hemodynamic function of different beat morphologies. Magn Reson Med 78:678-688, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Injectable Shear-Thinning Hydrogels for Minimally Invasive Delivery to Infarcted Myocardium to Limit Left Ventricular Remodeling.

BACKGROUND: Injectable, acellular biomaterials hold promise to limit left ventricular remodeling and heart failure precipitated by infarction through bulking or stiffening the infarct region. A material with tunable properties (eg, mechanics, degradation) that can be delivered percutaneously has not yet been demonstrated. Catheter-deliverable soft hydrogels with in vivo stiffening to enhance therapeutic efficacy achieve these requirements. METHODS AND RESULTS: We developed a hyaluronic acid hydrogel that uses a tandem crosslinking approach, where the first crosslinking (guest-host) enabled injection and localized retention of a soft (<1 kPa) hydrogel. A second crosslinking reaction (dual-crosslinking) stiffened the hydrogel (41.4±4.3 kPa) after injection. Posterolateral infarcts were investigated in an ovine model (n≥6 per group), with injection of saline (myocardial infarction control), guest-host hydrogels, or dual-crosslinking hydrogels. Computational (day 1), histological (1 day, 8 weeks), morphological, and functional (0, 2, and 8 weeks) outcomes were evaluated. Finite-element modeling projected myofiber stress reduction (>50%; P<0.001) with dual-crosslinking but not guest-host injection. Remodeling, assessed by infarct thickness and left ventricular volume, was mitigated by hydrogel treatment. Ejection fraction was improved, relative to myocardial infarction at 8 weeks, with dual-crosslinking (37% improvement; P=0.014) and guest-host (15% improvement; P=0.058) treatments. Percutaneous delivery via endocardial injection was investigated with fluoroscopic and echocardiographic guidance, with delivery visualized by magnetic resonance imaging. CONCLUSIONS: A percutaneous delivered hydrogel system was developed, and hydrogels with increased stiffness were found to be most effective in ameliorating left ventricular remodeling and preserving function. Ultimately, engineered systems such as these have the potential to provide effective clinical options to limit remodeling in patients after infarction.

Slice-by-Slice Pressure-Volume Loop Analysis Demonstrates Native Differences in Regional Cardiac Contractility and Response to Inotropic Agents.

BACKGROUND: Regional changes in diastolic and systolic properties after myocardial infarction contribute to adverse left ventricular (LV) remodeling. Regional function is currently assessed using load-dependent measures such as slice ejection fraction (sEF), wall motion abnormalities, or strain imaging. However, load-independent measures of cardiac function may be useful in the study of the infarction-induced remodeling. METHODS: In this study, we used a recently validated 2-dimensional (2D) real-time magnetic resonance imaging (MRI) technique to evaluate regional variations in load-independent slice-by-slice measures of systolic and diastolic function and compared the values to a load-dependent measure in 11 sheep at rest and during inotropic agent infusion. RESULTS: Slice-derived ejection fraction (sEF) was greater in the apex relative to the midventricular and basal regions, and inotropic infusion increased sEF in the base more than in the apex and midventricle. Slice-derived ESPVR (sESPVR) in the apex was significantly lower than in the midventricle and the base, and inotropic infusion increased sESPVR in the apical slices more than in the midventricle. Similarly, slice-derived volume-axis intercept V0 (sV0) was higher in the base relative to the midventricle and apex. sEDPVR did not demonstrate significant regional variations, but inotropic infusion resulted in a small increase in the apex. CONCLUSIONS: In conclusion, acquisition of slice-derived load-independent measures demonstrated variations that contradict those observed with load-dependent sEF. The approach may provide advanced slice-based measures of function during the LV remodeling process and aid in the development of therapies.

Integrated Regional Cardiac Hemodynamic Imaging and RNA Sequencing Reveal Corresponding Heterogeneity of Ventricular Wall Shear Stress and Endocardial Transcriptome.

BACKGROUND: Unlike arteries, in which regionally distinct hemodynamics are associated with phenotypic heterogeneity, the relationships between endocardial endothelial cell phenotype and intraventricular flow remain largely unexplored. We investigated regional differences in left ventricular wall shear stress and their association with endocardial endothelial cell gene expression. METHODS AND RESULTS: Local wall shear stress was calculated from 4-dimensional flow magnetic resonance imaging in 3 distinct regions of human (n=8) and pig (n=5) left ventricle: base, adjacent to the outflow tract; midventricle; and apex. In both species, wall shear stress values were significantly lower in the apex and midventricle relative to the base; oscillatory shear index was elevated in the apex. RNA sequencing of the endocardial endothelial cell transcriptome in pig left ventricle (n=8) at a false discovery rate ≤10% identified 1051 genes differentially expressed between the base and the apex and 327 between the base and the midventricle; no differentially expressed genes were detected at this false discovery rate between the apex and the midventricle. Enrichment analyses identified apical upregulation of genes associated with translation initiation including mammalian target of rapamycin, and eukaryotic initiation factor 2 signaling. Genes of mitochondrial dysfunction and oxidative phosphorylation were also consistently upregulated in the left ventricular apex, as were tissue factor pathway inhibitor (mean 50-fold) and prostacyclin synthase (5-fold)-genes prominently associated with antithrombotic protection. CONCLUSIONS: We report the first spatiotemporal measurements of wall shear stress within the left ventricle and linked regional hemodynamics to heterogeneity in ventricular endothelial gene expression, most notably to translation initiation and anticoagulation properties in the left ventricular apex, in which oscillatory shear index is increased and wall shear stress is decreased.

Measurement of Myocardial T1ρ with a Motion Corrected, Parametric Mapping Sequence in Humans.

PURPOSE: To develop a robust T1ρ magnetic resonance imaging (MRI) sequence for assessment of myocardial disease in humans. MATERIALS AND METHODS: We developed a breath-held T1ρ mapping method using a single-shot, T1ρ-prepared balanced steady-state free-precession (bSSFP) sequence. The magnetization trajectory was simulated to identify sources of T1ρ error. To limit motion artifacts, an optical flow-based image registration method was used to align T1ρ images. The reproducibility and accuracy of these methods was assessed in phantoms and 10 healthy subjects. Results are shown in 1 patient with pre-ventricular contractions (PVCs), 1 patient with chronic myocardial infarction (MI) and 2 patients with hypertrophic cardiomyopathy (HCM). RESULTS: In phantoms, the mean bias was 1.0 ± 2.7 msec (100 msec phantom) and 0.9 ± 0.9 msec (60 msec phantom) at 60 bpm and 2.2 ± 3.2 msec (100 msec) and 1.4 ± 0.9 msec (60 msec) at 80 bpm. The coefficient of variation (COV) was 2.2 (100 msec) and 1.3 (60 msec) at 60 bpm and 2.6 (100 msec) and 1.4 (60 msec) at 80 bpm. Motion correction improved the alignment of T1ρ images in subjects, as determined by the increase in Dice Score Coefficient (DSC) from 0.76 to 0.88. T1ρ reproducibility was high (COV < 0.05, intra-class correlation coefficient (ICC) = 0.85-0.97). Mean myocardial T1ρ value in healthy subjects was 63.5 ± 4.6 msec. There was good correspondence between late-gadolinium enhanced (LGE) MRI and increased T1ρ relaxation times in patients. CONCLUSION: Single-shot, motion corrected, spin echo, spin lock MRI permits 2D T1ρ mapping in a breath-hold with good accuracy and precision.

Quantification of Left Ventricular Function With Premature Ventricular Complexes Reveals Variable Hemodynamics.

BACKGROUND: Premature ventricular complexes (PVCs) are prevalent in the general population and are sometimes associated with reduced ventricular function. Current echocardiographic and cardiovascular magnetic resonance imaging techniques do not adequately address the effect of PVCs on left ventricular function. METHODS AND RESULTS: Fifteen subjects with a history of frequent PVCs undergoing cardiovascular magnetic resonance imaging had real-time slice volume quantification performed using a 2-dimensional (2D) real-time cardiovascular magnetic resonance imaging technique. Synchronization of 2D real-time imaging with patient ECG allowed for different beats to be categorized by the loading beat RR duration and beat RR duration. For each beat type, global volumes were quantified via summation over all slices covering the entire ventricle. Different patterns of ectopy, including isolated PVCs, bigeminy, trigeminy, and interpolated PVCs, were observed. Global functional measurement of the different beat types based on timing demonstrated differences in preload, stroke volume, and ejection fraction. An average of hemodynamic function was quantified for each subject depending on the frequency of each observed beat type. CONCLUSIONS: Application of real-time cardiovascular magnetic resonance imaging in patients with PVCs revealed differential contribution of PVCs to hemodynamics.

Impact of end-diastolic and end-systolic phase selection in the volumetric evaluation of cardiac MRI.

PURPOSE: To evaluate the impact of end-diastolic (ED) and end-systolic (ES) cardiac phase selection methods, since task force recommendations have neither provided quantitative evidence nor explored errors introduced by clinical shortcuts. MATERIALS AND METHODS: Multislice, short-axis cine images were collected in 60 clinical patients on a 1.5T scanner. User-initialized active contour segmentation software quantified global left ventricular (LV) volume across all cardiac phases. Different approaches for selection of ED and ES phase were evaluated by quantification of temporal and volumetric errors. RESULTS: For diastole, the mid-ventricular maximum slice volume coincided with maximum global volume in 82.1% of patients with ejection fraction (EF) ≥55% (P = 0.66) and 71.9% of patients with EF <55% (P = 0.28) and is an accurate approximation of maximum global volume while the first and last phases in a retrospectively electrocardiogram (ECG)-gated acquisition introduced differences in cardiac phase selection (P < 0.001) which led to large errors in measured volume in some patients (12.7 and 10.1 mL, respectively). For systole, post-systolic shortening occurred in a significantly higher number of patients with EF <55% (18.9%) compared to 3.6% of patients with EF ≥55% (P = 0.001), which differentially impacted end-systolic volume estimation. CONCLUSION: For end-diastolic phase selection, our results indicated that the use of the mid-ventricular slice volume maximum provided accurate volume estimates, while selection of the first or last cardiac phase introduced differences in measured volume. For end-systolic phase, patients with EF <55% had a higher prevalence of post-systolic shortening, which suggests aortic valve closure should be used to estimate end-systolic volume.

Nanoparticle Loaded Polymeric Microbubbles as Contrast Agents for Multimodal Imaging.

Ultrasound contrast agents are typically microbubbles (MB) with a gas core that is stabilized by a shell made of lipids, proteins, or polymers. The high impedance mismatch between the gas core and an aqueous environment produces strong contrast in ultrasound (US). Poly(lactic acid) (PLA) MB, previously developed in our laboratory, have been shown to be highly echogenic both in vitro and in vivo. Combining US with other imaging modalities such as fluorescence, magnetic resonance imaging (MRI), or computerized tomography (CT) could improve the accuracy of many US applications and provide more comprehensive diagnostic information. Furthermore, our MB have the capacity to house a drug in the PLA shell and create drug-loaded nanoparticles in situ when passing through an ultrasound beam. To create multimodal contrast agents, we hypothesized that the polymer shell of our PLA MB platform could accommodate additional payloads. In this study, we therefore modified our current MB by encapsulating nanoparticles including aqueous or organic quantum dots (QD), magnetic iron oxide nanoparticles (MNP), or gold nanoparticles (AuNP) to create bimodality platforms in a manner that minimally compromised the performance of each individual imaging technique.