Ultra-short echo time cardiovascular magnetic resonance of atherosclerotic carotid plaque.

BACKGROUND: Multi-contrast weighted cardiovascular magnetic resonance (CMR) allows detailed plaque characterisation and assessment of plaque vulnerability. The aim of this preliminary study was to show the potential of Ultra-short Echo Time (UTE) subtraction MR in detecting calcification. METHODS: 14 ex-vivo human carotid arteries were scanned using CMR and CT, prior to histological slide preparation. Two images were acquired using a double-echo 3D UTE pulse, one with a long TE and the second with an ultra-short TE, with the same TR. An UTE subtraction (DeltaUTE) image containing only ultra-short T2 (and T2*) signals was obtained by post-processing subtraction of the 2 UTE images. The DeltaUTE image was compared to the conventional 3D T1-weighted sequence and CT scan of the carotid arteries. RESULTS: In atheromatous carotid arteries, there was a 71% agreement between the high signal intensity areas on DeltaUTE images and CT scan. The same areas were represented as low signal intensity on T1W and areas of void on histology, indicating focal calcification. However, in 15% of all the scans there were some incongruent regions of high intensity on DeltaUTE that did not correspond with a high intensity signal on CT, and histology confirmed the absence of calcification. CONCLUSIONS: We have demonstrated that the UTE sequence has potential to identify calcified plaque. Further work is needed to fully understand the UTE findings

Intercentre reproducibility of cardiac apparent diffusion coefficient and fractional anisotropy in healthy volunteers

BACKGROUND: Diffusion tensor cardiac magnetic resonance (DT-CMR) enables probing of the microarchitecture of the myocardium, but the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) reported in healthy volunteers have been inconsistent. The aim of this study was to validate a stimulated-echo diffusion sequence using phantoms, and to assess the intercentre reproducibility of in-vivo diffusion measures using the sequence. METHODS AND RESULTS: A stimulated-echo, cardiac-gated DT-CMR sequence with a reduced-field-of-view, single-shot EPI readout was used at two centres with 3 T MRI scanners. Four alkane phantoms with known diffusivities were scanned at a single centre using a stimulated echo sequence and a spin-echo Stejskal-Tanner diffusion sequence. The median (maximum, minimum) difference between the DT-CMR sequence and Stejskal-Tanner sequence was 0.01 (0.04, 0.0006) × 10(-3) mm(2)/s (2%), and between the DT-CMR sequence and literature diffusivities was 0.02 (0.05, 0.006) × 10(-3) mm(2)/s (4%). The same ten healthy volunteers were scanned using the DT-CMR sequence at the two centres less than seven days apart. Average ADC and FA were calculated in a single mid-ventricular, short axis slice. Intercentre differences were tested for statistical significance at the p < 0.05 level using paired t-tests. The mean ADC ± standard deviation for all subjects averaged over both centres was 1.10 ± 0.06 × 10(-3) mm(2)/s in systole and 1.20 ± 0.09 × 10(-3) mm(2)/s in diastole; FA was 0.41 ± 0.04 in systole and 0.54 ± 0.03 in diastole. With similarly-drawn regions-of-interest, systolic ADC (difference 0.05 × 10(-3) mm(2)/s), systolic FA (difference 0.003) and diastolic FA (difference 0.01) were not statistically significantly different between centres (p > 0.05), and only the diastolic ADC showed a statistically significant, but numerically small, difference of 0.07 × 10(-3) mm(2)/s (p = 0.047). The intercentre, intrasubject coefficients of variance were: systolic ADC 7%, FA 6%; diastolic ADC 7%, FA 3%. CONCLUSIONS: This is the first study to demonstrate the accuracy of a stimulated-echo DT-CMR sequence in phantoms, and demonstrates the feasibility of obtaining reproducible ADC and FA in healthy volunteers at separate centres with well-matched sequences and processing

Effects of myocardial sheetlet sliding on left ventricular function

Left ventricle myocardium has a complex micro-architecture, which was revealed to consist of myocyte bundles arranged in a series of laminar sheetlets. Recent imaging studies demonstrated that these sheetlets re-orientated and likely slided over each other during the deformations between systole and diastole, and that sheetlet dynamics were altered during cardiomyopathy. However, the biomechanical effect of sheetlet sliding is not well-understood, which is the focus here. We conducted finite element simulations of the left ventricle (LV) coupled with a windkessel lumped parameter model to study sheetlet sliding, based on cardiac MRI of a healthy human subject, and modifications to account for hypertrophic and dilated geometric changes during cardiomyopathy remodeling. We modeled sheetlet sliding as a reduced shear stiffness in the sheet-normal direction and observed that (1) the diastolic sheetlet orientations must depart from alignment with the LV wall plane in order for sheetlet sliding to have an effect on cardiac function, that (2) sheetlet sliding modestly aided cardiac function of the healthy and dilated hearts, in terms of ejection fraction, stroke volume, and systolic pressure generation, but its effects were amplified during hypertrophic cardiomyopathy and diminished during dilated cardiomyopathy due to both sheetlet angle configuration and geometry, and that (3) where sheetlet sliding aided cardiac function, it increased tissue stresses, particularly in the myofibre direction. We speculate that sheetlet sliding is a tissue architectural adaptation to allow easier deformations of the LV walls so that LV wall stiffness will not hinder function, and to provide a balance between function and tissue stresses. A limitation here is that sheetlet sliding is modeled as a simple reduction in shear stiffness, without consideration of micro-scale sheetlet mechanics and dynamics

Realistic numerical simulations of diffusion tensor cardiovascular magnetic resonance: the effects of perfusion and membrane permeability

Purpose To study the sensitivity of diffusion tensor cardiovascular magnetic resonance (DT-CMR) to microvascular perfusion and changes in cell permeability. Methods Monte Carlo (MC) random walk simulations in the myocardium have been performed to simulate self-diffusion of water molecules in histology-based media with varying extracellular volume fraction (ECV) and permeable membranes. The effect of microvascular perfusion on simulations of the DT-CMR signal has been incorporated by adding the contribution of particles traveling through an anisotropic capillary network to the diffusion signal. The simulations have been performed considering three pulse sequences with clinical gradient strengths: monopolar stimulated echo acquisition mode (STEAM), monopolar pulsed-gradient spin echo (PGSE), and second-order motion-compensated spin echo (MCSE). Results Reducing ECV intensifies the diffusion restriction and incorporating membrane permeability reduces the anisotropy of the diffusion tensor. Widening the intercapillary velocity distribution results in increased measured diffusion along the cardiomyocytes long axis when the capillary networks are anisotropic. Perfusion amplifies the mean diffusivity for STEAM while the opposite is observed for short diffusion encoding time sequences (PGSE and MCSE). Conclusion The effect of perfusion on the measured diffusion tensor is reduced using an increased reference b-value. Our results pave the way for characterization of the response of DT-CMR to microstructural changes underlying cardiac pathology and highlight the higher sensitivity of STEAM to permeability and microvascular circulation due to its longer diffusion encoding time

Relationship between cardiac diffusion tensor imaging parameters and anthropometrics in healthy volunteers

Background: In vivo cardiac diffusion tensor imaging (cDTI) is uniquely capable of interrogating laminar myocardial dynamics non-invasively. A comprehensive dataset of quantative parameters and comparison with subject anthropometrics is required. Methods: cDTI was performed at 3T with a diffusion weighted STEAM sequence. Data was acquired from the mid left ventricle in 43 subjects during the systolic and diastolic pauses. Global and regional values were determined for fractional anisotropy (FA), mean diffusivity (MD), helix angle gradient (HAg, degrees/%depth) and the secondary eigenvector angulation (E2A). Regression analysis was performed between global values and subject anthropometrics. Results: All cDTI parameters displayed regional heterogeneity. The RR interval had a significant, but clinically small effect on systolic values for FA, HAg and E2A. Male sex and increasing left ventricular end diastolic volume were associated with increased systolic HAg. Diastolic HAg and systolic E2A were both directly related to left ventricular mass and body surface area. There was an inverse relationship between E2A mobility and both age and ejection fraction. Conclusions: Future interpretations of quantitative cDTI data should take into account anthropometric variations observed with patient age, body surface area and left ventricular measurements. Further work determining the impact of technical factors such as strain and SNR is required

Evaluation of the impact of strain correction on the orientation of cardiac diffusion tensors with in vivo and ex vivo porcine hearts

Purpose To evaluate the importance of strain-correcting stimulated echo acquisition mode echo-planar imaging cardiac diffusion tensor imaging. Methods Healthy pigs (n = 11) were successfully scanned with a 3D cine displacement-encoded imaging with stimulated echoes and a monopolar-stimulated echo-planar imaging diffusion tensor imaging sequence at 3 T during diastasis, peak systole, and strain sweet spots in a midventricular short-axis slice. The same diffusion tensor imaging sequence was repeated ex vivo after arresting the hearts in either a relaxed (KCl-induced) or contracted (BaCl2-induced) state. The displacement-encoded imaging with stimulated echoes data were used to strain-correct the in vivo cardiac diffusion tensor imaging in diastole and systole. The orientation of the primary (helix angles) and secondary (E2A) diffusion eigenvectors was compared with and without strain correction and to the strain-free ex vivo data. Results Strain correction reduces systolic E2A significantly when compared without strain correction and ex vivo (median absolute E2A = 34.3° versus E2A = 57.1° (P = 0.01), E2A = 60.5° (P = 0.006), respectively). The systolic distribution of E2A without strain correction is closer to the contracted ex vivo distribution than with strain correction, root mean square deviation of 0.027 versus 0.038. Conclusions The current strain-correction model amplifies the contribution of microscopic strain to diffusion resulting in an overcorrection of E2A. Results show that a new model that considers cellular rearrangement is required

The impact of signal-to-noise ratio, diffusion-weighted directions and image resolution in cardiac diffusion tensor imaging - insights from the ex-vivo rat heart

Background: Cardiac diffusion tensor imaging (DTI) is limited by scan time and signal-to-noise (SNR) restrictions. This invariably leads to a trade-off between the number of averages, diffusion-weighted directions (ND), and image resolution. Systematic evaluation of these parameters is therefore important for adoption of cardiac DTI in clinical routine where time is a key constraint. Methods: High quality reference DTI data were acquired in five ex-vivo rat hearts. We then retrospectively set 2 ≤ SNR ≤ 97, 7 ≤ ND ≤ 61, varied the voxel volume by up to 192-fold and investigated the impact on the accuracy and precision of commonly derived parameters. Results: For maximal scan efficiency, the accuracy and precision of the mean diffusivity is optimised when SNR is maximised at the expense of ND. With typical parameter settings used clinically, we estimate that fractional anisotropy may be overestimated by up to 13% with an uncertainty of ±30%, while the precision of the sheetlet angles may be as poor as ±31°. Although the helix angle has better precision of ±14°, the transmural range of helix angles may be under-estimated by up to 30° in apical and basal slices, due to partial volume and tapering myocardial geometry. Conclusions: These findings inform a baseline of understanding upon which further issues inherent to in-vivo cardiac DTI, such as motion, strain and perfusion, can be considered. Furthermore, the reported bias and reproducibility provides a context in which to assess cardiac DTI biomarkers

Assessment of myocardial microstructural dynamics by in vivo diffusion tensor cardiac magnetic resonance

Background: Cardiomyocytes are organized in microstructures termed sheetlets that reorientate during left ventricular thickening. Diffusion tensor cardiac magnetic resonance (DT-CMR) may enable noninvasive interrogation of in vivo cardiac microstructural dynamics. Dilated cardiomyopathy (DCM) is a condition of abnormal myocardium with unknown sheetlet function. Objectives: This study sought to validate in vivo DT-CMR measures of cardiac microstructure against histology, characterize microstructural dynamics during left ventricular wall thickening, and apply the technique in hypertrophic cardiomyopathy (HCM) and DCM. Methods: In vivo DT-CMR was acquired throughout the cardiac cycle in healthy swine, followed by in situ and ex vivo DT-CMR, then validated against histology. In vivo DT-CMR was performed in 19 control subjects, 19 DCM, and 13 HCM patients. Results: In swine, a DT-CMR index of sheetlet reorientation (E2A) changed substantially (E2A mobility ∼46°). E2A changes correlated with wall thickness changes (in vivo r2 = 0.75; in situ r2 = 0.89), were consistently observed under all experimental conditions, and accorded closely with histological analyses in both relaxed and contracted states. The potential contribution of cyclical strain effects to in vivo E2A was ∼17%. In healthy human control subjects, E2A increased from diastole (18°) to systole (65°; p < 0.001; E2A mobility = 45°). HCM patients showed significantly greater E2A in diastole than control subjects did (48°; p < 0.001) with impaired E2A mobility (23°; p < 0.001). In DCM, E2A was similar to control subjects in diastole, but systolic values were markedly lower (40°; p < 0.001) with impaired E2A mobility (20°; p < 0.001). Conclusions: Myocardial microstructure dynamics can be characterized by in vivo DT-CMR. Sheetlet function was abnormal in DCM with altered systolic conformation and reduced mobility, contrasting with HCM, which showed reduced mobility with altered diastolic conformation. These novel insights significantly improve understanding of contractile dysfunction at a level of noninvasive interrogation not previously available in humans