Henrik Haraldsson

Distribution of normal human left ventricular myofiber stress at end diastole and end systole: a target for in silico design of heart failure treatments

Ventricular wall stress is believed to be responsible for many physical mechanisms taking place in the human heart, including ventricular remodeling, which is frequently associated with heart failure. Therefore, normalization of ventricular wall stress is the cornerstone of many existing and new treatments for heart failure. In this paper, we sought to construct reference maps of normal ventricular wall stress in humans that could be used as a target for in silico optimization studies of existing and potential new treatments for heart failure. To do so, we constructed personalized computational models of the left ventricles of five normal human subjects using magnetic resonance images and the finite-element method. These models were calibrated using left ventricular volume data extracted from magnetic resonance imaging (MRI) and validated through comparison with strain measurements from tagged MRI (950 ± 170 strain comparisons/subject). The calibrated passive material parameter values were C0 = 0.115 ± 0.008 kPa and B0 = 14.4 ± 3.18; the active material parameter value was Tmax = 143 ± 11.1 kPa. These values could serve as a reference for future construction of normal human left ventricular computational models. The differences between the predicted and the measured circumferential and longitudinal strains in each subject were 3.4 ± 6.3 and 0.5 ± 5.9%, respectively. The predicted end-diastolic and end-systolic myofiber stress fields for the five subjects were 2.21 ± 0.58 and 16.54 ± 4.73 kPa, respectively. Thus these stresses could serve as targets for in silico design of heart failure treatments.

Vascular Imaging With Ferumoxytol as a Contrast Agent

OBJECTIVE Ferumoxytol is increasingly reported as an alternative to gadolinium-based contrast agents for MR angiography (MRA), particularly for patients with renal failure. This article summarizes more than 3 years of clinical experience with ferumoxytol-enhanced MRA for a range of indications and anatomic regions. CONCLUSION Ferumoxytol-enhanced MRA has many advantages including that it is safe for patients with renal failure and provides a lengthy plateau of vascular signal as a blood pool agent that allows longer navigated MRA sequences.

Simultaneous three-dimensional myocardial T1 and T2 mapping in one breath hold with 3D-QALAS

BackgroundQuantification of the longitudinal- and transverse relaxation time in the myocardium has shown to provide important information in cardiac diagnostics. Methods for cardiac relaxation time mapping generally demand a long breath hold to measure either T1 or T2 in a single 2D slice. In this paper we present and evaluate a novel method for 3D interleaved T1 and T2 mapping of the whole left ventricular myocardium within a single breath hold of 15 heartbeats.MethodsThe 3D-QALAS (3D-quantification using an interleaved Look-Locker acquisition sequence with T2 preparation pulse) is based on a 3D spoiled Turbo Field Echo sequence using inversion recovery with interleaved T2 preparation. Quantification of both T1 and T2 in a volume of 13 slices with a resolution of 2.0x2.0x6.0 mm is obtained from five measurements by using simulations of the longitudinal magnetizations Mz. This acquisition scheme is repeated three times to sample k-space. The method was evaluated both in-vitro (validated against Inversion Recovery and Multi Echo) and in-vivo (validated against MOLLI and Dual Echo).ResultsIn-vitro, a strong relation was found between 3D-QALAS and Inversion Recovery (R = 0.998; N = 10; p < 0.01) and between 3D-QALAS and Multi Echo (R = 0.996; N = 10; p < 0.01). The 3D-QALAS method showed no dependence on e.g. heart rate in the interval of 40–120 bpm. In healthy myocardium, the mean T1 value was 1083 ± 43 ms (mean ± SD) for 3D-QALAS and 1089 ± 54 ms for MOLLI, while the mean T2 value was 50.4 ± 3.6 ms 3D-QALAS and 50.3 ± 3.5 ms for Dual Echo. No significant difference in in-vivo relaxation times was found between 3D-QALAS and MOLLI (N = 10; p = 0.65) respectively 3D-QALAS and Dual Echo (N = 10; p = 0.925) for the ten healthy volunteers.ConclusionsThe 3D-QALAS method has demonstrated good accuracy and intra-scan variability both in-vitro and in-vivo. It allows rapid acquisition and provides quantitative information of both T1 and T2 relaxation times in the same scan with full coverage of the left ventricle, enabling clinical application in a broader spectrum of cardiac disorders.

Ascending thoracic aortic aneurysm wall stress analysis using patient-specific finite element modeling of in vivo magnetic resonance imaging†

OBJECTIVES Rupture/dissection of ascending thoracic aortic aneurysms (aTAAs) carries high mortality and occurs in many patients who did not meet size criteria for elective surgery. Elevated wall stress may better predict adverse events, but cannot be directly measured in vivo, rather determined from finite element (FE) simulations. Current computational models make assumptions that limit accuracy, most commonly using in vivo imaging geometry to represent zero-pressure state. Accurate patient-specific wall stress requires models with zero-pressure three-dimensional geometry, material properties, wall thickness and residual stress. We hypothesized that wall stress calculated from in vivo imaging geometry at systemic pressure underestimates that using zero-pressure geometry. We developed a novel method to derive zero-pressure geometry from in vivo imaging at systemic pressure. The purpose of this study was to develop the first patient-specific aTAA models using magnetic resonance imaging (MRI) to assess material properties and zero-pressure geometry. Wall stress results from FE models using systemic pressure were compared with those from models using zero-pressure correction. METHODS Patients with aTAAs <5 cm underwent ECG-gated computed tomography angiography (CTA) and displacement encoding with stimulated echo (DENSE)-MRI. CTA lumen geometry was used to create surface contour meshes of aTAA geometry. DENSE-MRI measured cyclic aortic wall strain from which wall material property was derived. Zero- and systemic pressure geometries were created. Simulations were loaded to systemic pressure using the ABAQUS FE software. Wall stress analyses were compared between zero-pressure-corrected and systemic pressure geometry FE models. RESULTS Peak first principal wall stress (primarily aligned in the circumferential direction) at systolic pressure for the zero-pressure correction models was 430.62 ± 69.69 kPa, whereas that without zero-pressure correction was 312.55 ± 39.65 kPa (P = 0.004). Peak second principal wall stress (primarily aligned in the longitudinal direction) at systolic pressure for the zero-pressure correction models was 200.77 ± 43.13 kPa, whereas that without zero-stress correction was 156.25 ± 25.55 kPa (P = 0.02). CONCLUSIONS Previous FE aTAA models from in vivo CT and MRI have not accounted for zero-pressure geometry or patient-specific material property. We demonstrated that zero-pressure correction significantly impacts wall stress results. Future computational models that use wall stress to predict aTAA adverse events must take into account zero-pressure geometry and patient material property for accurate wall stress determination.

In vivo SNR in DENSE MRI; temporal and regional effects of field strength, receiver coil sensitivity and flip angle strategies.

AIM The influences on the signal-to-noise ratio (SNR) of Displacement ENcoding with Stimulated Echoes (DENSE) MRI of field strength, receiver coil sensitivity and choice of flip angle strategy have been previously investigated individually. In this study, all of these parameters have been investigated in the same setting, and a mutual comparison of their impact on SNR is presented. MATERIALS AND METHODS Ten healthy volunteers were imaged in a 1.5 T and a 3 T MRI system, using standard five- or six-channel cardiac coils as well as 32-channel coils, with four different excitation patterns. Variation of spatial coil sensitivity was assessed by regional SNR analysis. RESULTS SNR ranging from 2.8 to 30.5 was found depending on the combination of excitation patterns, coil sensitivity and field strength. The SNR at 3 T was 53±26% higher than at 1.5 T (P<.001), whereas spatial differences of 59±26% were found in the ventricle (P<.001). Thirty-two-channel coils provided 52±29% higher SNR compared to standard five- or six-channel coils (P<.001). A fixed flip angle strategy provided an excess of 50% higher SNR in half of the imaged cardiac cycle compared to a sweeping flip angle strategy, and a single-phase acquisition provided a sixfold increase of SNR compared to a cine acquisition. CONCLUSION The effect of field strength and receiver coil sensitivity influences the SNR with the same order of magnitude, whereas flip angle strategy can have a larger effect on SNR. Thus, careful choice of imaging hardware in combination with adaptation of the acquisition protocol is crucial in order to realize sufficient SNR in DENSE MRI.

Isotropic 3D black blood MRI of abdominal aortic aneurysm wall and intraluminal thrombus

INTRODUCTION The aortic wall and intraluminal thrombus (ILT) have been increasingly studied as potential markers of progressive disease with abdominal aortic aneurysms (AAAs). Our goal was to develop a high resolution, 3D black blood MR technique for AAA wall and ILT imaging within a clinically acceptable scan time. METHODS Twenty two patients with AAAs (maximal diameter 4.3±1.0cm), along with five healthy volunteers, were imaged at 3T with a 3D T1-weighted fast-spin-echo sequence using variable flip angle trains (SPACE) with a preparation pulse (DANTE) for suppressing blood signal. Volunteers and ten patients were also scanned with SPACE alone for comparison purposes. The signal to noise ratio (SNR) and the aortic wall/ILT to lumen contrast to noise ratio (CNR) were measured. Qualitative image scores (1-4 scale) assessing the inner lumen and outer wall boundaries of AAA were performed by two blinded reviewers. In patients with ILT, the ratio of ILT signal intensity (ILTSI) over psoas muscle SI (MuscleSI) was calculated, and the signal heterogeneity of ILT was quantified as standard deviation (SD) over the mean. RESULTS All subjects were imaged successfully with an average scan time of 7.8±0.7minutes. The DANTE preparation pulse for blood suppression substantially reduced flow artifacts in SPACE with lower lumen SNR (8.8 vs. 21.4, p<0.001) and improved the wall/ILT to lumen CNR (9.9 vs. 6.3, p<0.001) in patients. Qualitative assessment showed improved visualization of lumen boundaries (73% higher scores on average, p=0.01) and comparable visualization of outer wall boundary (p>0.05). ILT was present in ten patients, with relatively high signal and a wide SD (average ILTSI/MuscleSI 1.42±0.48 (range 0.75-2.11)) and with SD/mean of 27.7%±6.6% (range 19.6%-39.4%). CONCLUSION High resolution, 3D black blood MRI of AAAs can be achieved in a clinical accepted scan time with reduction of flow artifacts using the DANTE preparation pulse. Signal characteristics of ILT can be quantified and may be used for improved patient-specific risk stratification.

Clinical experience of strain imaging using DENSE for detecting infarcted cardiac segments.

BackgroundWe hypothesised that myocardial deformation determined with magnetic resonance imaging (MRI) will detect myocardial scar.MethodsDisplacement Encoding with Stimulated Echoes (DENSE) was used to calculate left ventricular strain in 125 patients (29 women and 96 men) with suspected coronary artery disease. The patients also underwent cine imaging and late gadolinium enhancement. 57 patients had a scar area >1 % in at least one segment, 23 were considered free from coronary artery disease (control group) and 45 had pathological findings but no scar (mixed group). Peak strain was calculated in eight combinations: radial and circumferential strain in transmural, subendocardial and epicardial layers derived from short axis acquisition, and transmural longitudinal and radial strain derived from long axis acquisitions. In addition, the difference between strain in affected segments and reference segments, “differential strain”, from the control group was analysed.ResultsIn receiver-operator-characteristic analysis for the detection of 50 % transmurality, circumferential strain performed best with area-under-curve (AUC) of 0.94. Using a cut-off value of -17 %, sensitivity was 95 % at a specificity of 80 %. AUC did not further improve with differential strain. There were significant differences between the control group and global strain circumferential direction (-17 % versus -12 %) and in the longitudinal direction (-13 % versus -10 %). Interobserver and scan-rescan reproducibility was high with an intraclass correlation coefficient (ICC) >0.93.ConclusionsDENSE-derived circumferential strain may be used for the detection of myocardial segments with >50 % scar area. The repeatability of strain is satisfactory. DENSE-derived global strain agrees with other global measures of left ventricular ejection fraction.

Improved estimation and visualization of two-dimensional myocardial strain rate using MR velocity mapping

To estimate regional myocardial strain rate, with reduced sensitivity to noise and velocities outside the region of interest, and provide a visualization of the spatial variation of the obtained tensor field within the myocardium.

Feasibility of asymmetric stretch assessment in the ascending aortic wall with DENSE cardiovascular magnetic resonance

BackgroundVessel 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.MethodsAortic 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.ResultsAnalysis 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).ConclusionsEvaluation 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.

Single-breath-hold multiple-slice DENSE MRI.

A method to acquire multiple displacement encoded slices within a single breath hold is presented. Efficiency is improved over conventional DENSE without compromising image quality by readout of multiple slices in the same cardiac cycle, thus utilizing the position‐encoded stimulated echo available in the whole heart. The method was evaluated by comparing strain values obtained using the proposed method to strain values obtained by conventional separate breath‐hold single‐slice DENSE acquisitions. Good agreement (Lagrangian E2 strain bias = 0.000, 95% limits of agreement ± 0.04, root‐mean‐square‐difference 0.02 [9.4% of mean end‐systolic E2]) was found between the methods, indicating that the proposed method can replace a multiple breath‐hold acquisition. Eliminating the need for multiple breath holds reduces the risk of changes in breath‐hold positions or heart rate, results in higher patient comfort, and facilitates inclusion of DENSE in a clinical routine protocol. Magn Reson Med 63:1411–1414, 2010.