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5.  Validation of in vivo 2D displacements from spiral cine DENSE at 3T 
Displacement 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.
Two-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.
The displacement accuracy of spiral cine DENSE was not different between 3T and 1.5T (1.2 ± 0.3 mm and 1.2 ± 0.4 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 1.4 ± 0.3.
The 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.
PMCID: PMC4311418  PMID: 25634468
DENSE; Displacement; Cardiac mechanics; Spiral; Strain; Torsion; 3T; Cardiovascular magnetic resonance
6.  Facile non-hydrothermal synthesis of oligosaccharides coated sub-5 nm magnetic iron oxide nanoparticles with dual MRI contrast enhancement effect 
Ultrafine sub-5 nm magnetic iron oxide nanoparticles coated with oligosaccharides (SIO) with dual T1-T2 weighted contrast enhancing effect and fast clearance has been developed as magnetic resonance imaging (MRI) contrast agent. Excellent water solubility, biocompatibility and high stability of such sub-5 nm SIO nanoparticles were achieved by using the “in-situ polymerization” coating method, which enables glucose forming oligosaccharides directly on the surface of hydrophobic iron oxide nanocrystals. Reported ultrafine SIO nanoparticles exhibit a longitudinal relaxivity (r1) of 4.1 mM−1s−1 and a r1/r2 ratio of 0.25 at 3 T (clinical field strength), rendering improved T1 or “brighter” contrast enhancement in T1-weighted MRI in addition to typical T2 or “darkening” contrast of conventional iron oxide nanoparticles. Such dual contrast effect can be demonstrated in liver imaging with T2 “darkening” contrast in the liver parenchyma but T1 “bright” contrast in the hepatic vasculature. More importantly, this new class of ultrafine sub-5 nm iron oxide nanoparticles showed much faster body clearance than those with larger sizes, promising better safety for clinical applications.
PMCID: PMC4147377  PMID: 25181490
12.  Semi-automated left ventricular segmentation based on a guide point model approach for 3D cine DENSE cardiovascular magnetic resonance 
The most time consuming and limiting step in three dimensional (3D) cine displacement encoding with stimulated echoes (DENSE) MR image analysis is the demarcation of the left ventricle (LV) from its surrounding anatomical structures. The aim of this study is to implement a semi-automated segmentation algorithm for 3D cine DENSE CMR using a guide point model approach.
A 3D mathematical model is fitted to guide points which were interactively placed along the LV borders at a single time frame. An algorithm is presented to robustly propagate LV epicardial and endocardial surfaces of the model using the displacement information encoded in the phase images of DENSE data. The accuracy, precision and efficiency of the algorithm are tested.
The model-defined contours show good accuracy when compared to the corresponding manually defined contours as similarity coefficients Dice and Jaccard consist of values above 0.7, while false positive and false negative measures show low percentage values. This is based on a measure of segmentation error on intra- and inter-observer spatial overlap variability. The segmentation algorithm offers a 10-fold reduction in the time required to identify LV epicardial and endocardial borders for a single 3D DENSE data set.
A semi-automated segmentation method has been developed for 3D cine DENSE CMR. The algorithm allows for contouring of the first cardiac frame where blood-myocardium contrast is almost nonexistent and reduces the time required to segment a 3D DENSE data set significantly.
PMCID: PMC3903450  PMID: 24423129
Cardiovascular MR; DENSE; Segmentation; Guide point modeling
13.  Feasibility of asymmetric stretch assessment in the ascending aortic wall with DENSE cardiovascular magnetic resonance 
Vessel diameter is the principal imaging parameter assessed clinically for aortic disease, but adverse events can occur at normal diameters. Aortic stiffness has been studied as an additional imaging-based risk factor, and has been shown to be an independent predictor of cardiovascular morbidity and all-cause mortality. Reports suggest that some aortic pathology is asymmetric around the vessel circumference, a feature which would not be identified with current imaging approaches. We propose that this asymmetry may be revealed using Displacement Encoding with Stimulated Echoes (DENSE). The objective of this study is to investigate the feasibility of assessing asymmetric stretch in healthy and diseased ascending aortas using DENSE.
Aortic wall displacement was assessed with DENSE cardiovascular magnetic resonance (CMR) in 5 volunteers and 15 consecutive patients. Analysis was performed in a cross-sectional plane through the ascending aorta at the pulmonary artery. Displacement data was used to determine the wall stretch between the expanded and resting states of the aorta, in four quadrants around the aortic circumference.
Analysis of variance (ANOVA) did not only show significant differences in stretch between groups of volunteers (p < 0.001), but also significant differences in stretch along the circumference of the aorta (p < 0.001), indicating an asymmetric stretch pattern. Furthermore, there is a significant difference in the asymmetry between volunteers and different groups of patients (p < 0.01).
Evaluation of asymmetric stretch is feasible in the ascending aorta with DENSE CMR. Clear differences in stretch are seen between patients and volunteers, with asymmetric patterns demonstrated around the aortic circumference.
PMCID: PMC3895850  PMID: 24400865
Aorta; DENSE; Stretch; Stiffness; Bicuspid aortic valves; Cardiovascular magnetic resonance
14.  T1-Weighted Ultrashort Echo Time Method for Positive Contrast Imaging of Magnetic Nanoparticles and Cancer Cells Bound With the Targeted Nanoparticles 
To obtain positive contrast based on T1 weighting from magnetic iron oxide nanoparticle (IONP) using ultrashort echo time (UTE) imaging and investigate quantitative relationship between positive contrast and the core size and concentration of IONPs.
Materials and Methods
Solutions of IONPs with different core sizes and concentrations were prepared. T1 and T2 relaxation times of IONPs were measured using the inversion recovery turbo spin echo (TSE) and multi-echo spin echo sequences at 3 Tesla. T1-weighted UTE gradient echo and T2-weighted TSE sequences were used to image IONP samples. U87MG glioblastoma cells bound with arginine-glycine-aspartic acid (RGD) peptide and IONP conjugates were scanned using UTE, T1 and T2-weighted sequences.
Positive contrast was obtained by UTE imaging from IONPs with different core sizes and concentrations. The relative-contrast-to-water ratio of UTE images was three to four times higher than those of T2-weighted TSE images. The signal intensity increases as the function of the core size and concentration. Positive contrast was also evident in cell samples bound with RGD-IONPs.
UTE imaging allows for imaging of IONPs and IONP bound tumor cells with positive contrast and provides contrast enhancement and potential quantification of IONPs in molecular imaging applications.
PMCID: PMC3785614  PMID: 21182139
magnetic nanoparticle; magnetic resonance imaging; iron oxide; ultrashort TE; molecular Imaging
18.  Mapping right ventricular myocardial mechanics using 3D cine DENSE cardiovascular magnetic resonance 
The mechanics of the right ventricle (RV) are not well understood as studies of the RV have been limited. This is, in part, due to the RV's thin wall, asymmetric geometry and irregular motion. However, the RV plays an important role in cardiovascular function. This study aims to describe the complex mechanics of the healthy RV using three dimensional (3D) cine displacement encoding with stimulated echoes (DENSE) cardiovascular magnetic resonance (CMR).
Whole heart 3D cine DENSE data were acquired from five healthy volunteers. Tailored post-processing algorithms for RV mid-wall tissue tracking and strain estimation are presented. A method for sub-dividing the RV into four regions according to anatomical land marks is proposed, and the temporal evolution of strain was assessed in these regions.
The 3D cine DENSE tissue tracking methods successfully capture the motion and deformation of the RV at a high spatial resolution in all volunteers. The regional Lagrangian peak surface strain and time to peak values correspond with previous studies using myocardial tagging, DENSE and strain encoded CMR. The inflow region consistently displays lower peak strains than the apical and outflow regions, and the time to peak strains suggest RV mechanical activation in the following order: inflow, outflow, mid, then apex.
Model-free techniques have been developed to study the myocardial mechanics of the RV at a high spatial resolution using 3D cine DENSE CMR. The consistency of the regional RV strain patterns across healthy subjects is encouraging and the techniques may have clinical utility in assessing disrupted RV mechanics in the diseased heart.
PMCID: PMC3311142  PMID: 22236389
displacement encoding; DENSE; right ventricle; cardiac function; strain
19.  Improving the Magnetic Resonance Imaging Contrast and Detection Methods with Engineered Magnetic Nanoparticles 
Theranostics  2012;2(1):86-102.
Engineering and functionalizing magnetic nanoparticles have been an area of the extensive research and development in the biomedical and nanomedicine fields. Because their biocompatibility and toxicity are well investigated and better understood, magnetic nanoparticles, especially iron oxide nanoparticles, are better suited materials as contrast agents for magnetic resonance imaging (MRI) and for image-directed delivery of therapeutics. Given tunable magnetic properties and various surface chemistries from the coating materials, most applications of engineered magnetic nanoparticles take advantages of their superb MRI contrast enhancing capability as well as surface functionalities. It has been found that MRI contrast enhancement by magnetic nanoparticles is highly dependent on the composition, size and surface properties as well as the degree of aggregation of the nanoparticles. Therefore, understanding the relationships between these intrinsic parameters and the relaxivities that contribute to MRI contrast can lead to establishing essential guidance that may direct the design of engineered magnetic nanoparticles for theranostics applications. On the other hand, new contrast mechanism and imaging strategy can be developed based on the novel properties of engineered magnetic nanoparticles. This review will focus on discussing the recent findings on some chemical and physical properties of engineered magnetic nanoparticles affecting the relaxivities as well as the impact on MRI contrast. Furthermore, MRI methods for imaging magnetic nanoparticles including several newly developed MRI approaches aiming at improving the detection and quantification of the engineered magnetic nanoparticles are described.
PMCID: PMC3263519  PMID: 22272222
magnetic nanoparticles; engineering; functionalizing; magnetic resonance imaging
20.  Comprehensive Cardiovascular magnetic resonance of myocardial mechanics in mice using three-dimensional cine DENSE 
Quantitative noninvasive imaging of myocardial mechanics in mice enables studies of the roles of individual genes in cardiac function. We sought to develop comprehensive three-dimensional methods for imaging myocardial mechanics in mice.
A 3D cine DENSE pulse sequence was implemented on a 7T small-bore scanner. The sequence used three-point phase cycling for artifact suppression and a stack-of-spirals k-space trajectory for efficient data acquisition. A semi-automatic 2D method was adapted for 3D image segmentation, and automated 3D methods to calculate strain, twist, and torsion were employed. A scan protocol that covered the majority of the left ventricle in a scan time of less than 25 minutes was developed, and seven healthy C57Bl/6 mice were studied.
Using these methods, multiphase normal and shear strains were measured, as were myocardial twist and torsion. Peak end-systolic values for the normal strains at the mid-ventricular level were 0.29 ± 0.17, -0.13 ± 0.03, and -0.18 ± 0.14 for Err, Ecc, and Ell, respectively. Peak end-systolic values for the shear strains were 0.00 ± 0.08, 0.04 ± 0.12, and 0.03 ± 0.07 for Erc, Erl, and Ecl, respectively. The peak end-systolic normalized torsion was 5.6 ± 0.9°.
Using a 3D cine DENSE sequence tailored for cardiac imaging in mice at 7 T, a comprehensive assessment of 3D myocardial mechanics can be achieved with a scan time of less than 25 minutes and an image analysis time of approximately 1 hour.
PMCID: PMC3278394  PMID: 22208954
21.  Imaging Three-Dimensional Myocardial Mechanics Using Navigator-gated Volumetric Spiral Cine DENSE MRI 
A navigator-gated 3D spiral cine displacement encoding with stimulated echoes (DENSE) pulse sequence for imaging 3D myocardial mechanics was developed. In addition, previously-described 2D post-processing algorithms including phase unwrapping, tissue tracking, and strain tensor calculation for the left ventricle (LV) were extended to 3D. These 3D methods were evaluated in 5 healthy volunteers, using 2D cine DENSE and historical 3D myocardial tagging as reference standards. With an average scan time of 20.5 ± 5.7 minutes, 3D data sets with a matrix size of 128 × 128 × 22, voxel size of 2.8 × 2.8 × 5.0 mm3, and temporal resolution of 32 ms were obtained with displacement encoding in three orthogonal directions. Mean values for end-systolic mid-ventricular mid-wall radial, circumferential, and longitudinal strain were 0.33 ± 0.10, −0.17 ± 0.02, and −0.16 ± 0.02, respectively. Transmural strain gradients were detected in the radial and circumferential directions, reflecting high spatial resolution. Good agreement by linear correlation and Bland-Altman analysis was achieved when comparing normal strains measured by 2D and 3D cine DENSE. Also, the 3D strains, twist, and torsion results obtained by 3D cine DENSE were in good agreement with historical values measured by 3D myocardial tagging.
PMCID: PMC2946451  PMID: 20574967
Three dimensional; DENSE; myocardial mechanics; cardiac function; stimulated echo; strain
25.  Calf Muscle Perfusion at Peak Exercise in Peripheral Arterial Disease: Measurement by First-Pass Contrast-Enhanced Magnetic Resonance Imaging 
To develop a contrast-enhanced magnetic resonance (MR) technique to measure skeletal muscle perfusion in peripheral arterial disease (PAD).
Materials and Methods
A total of 11 patients (age = 61 ± 11 years) with moderate symptomatic PAD (ankle-brachial index [ABI] = 0.75 ± 0.08) and 22 normals were studied using an MR-compatible ergometer. PAD and normalmax (Nlmax; N = 11) exercised to exhaustion. Nllow (N = 11) exercised to the same workload achieved by PAD. At peak exercise, 0.1 mm/kg of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) was infused at 3–4 cm3/second followed by a saline flush at the same rate. A dual-contrast gradient echo (GRE) sequence enabled simultaneous acquisition of muscle perfusion and arterial input function (AIF). The perfusion index (PI) was defined as the slope of the time-intensity curve (TIC) in muscle divided by the arterial TIC slope.
Median workload was 120 Joules in PAD, 210 Joules in Nllow, and 698 Joules in Nlmax (P < 0.001 vs. Nllow and PAD). Median PI was 0.29 in PAD (25th and 75th percentiles [%] = 0.20, 0.40), 0.48 in Nllow (25th, 75th % = 0.36, 0.62; P < 0.02 vs. PAD), and 0.69 in Nlmax (25th, 75th % = 0.5, 0.77; P < 0.001 vs. PAD). Area under the ROC-curve for PI differentiating patients from Nlmax was 0.95 (95% confidence interval [CI] = 0.77–0.99).
Peak-exercise measurement of lower limb perfusion with dual-contrast, first-pass MR distinguishes PAD from normals. This method may be useful in the study of novel therapies for PAD.
PMCID: PMC2930771  PMID: 17410566
peripheral vascular disease; perfusion; exercise; claudication

Results 1-25 (29)