Autocalibrated cardiac tissue phase mapping with multiband imaging and k-t acceleration.

PURPOSE: To develop an autocalibrated multiband (MB) CAIPIRINHA acquisition scheme with in-plane k-t acceleration enabling multislice three-directional tissue phase mapping in one breath-hold. METHODS: A k-t undersampling scheme was integrated into a time-resolved electrocardiographic-triggered autocalibrated MB gradient-echo sequence. The sequence was used to acquire data on 4 healthy volunteers with MB factors of two (MB2) and three (MB3), which were reconstructed using a joint reconstruction algorithm that tackles both k-t and MB acceleration. Forward simulations of the imaging process were used to tune the reconstruction model hyperparameters. Direct comparisons between MB and single-band tissue phase-mapping measurements were performed. RESULTS: Simulations showed that the velocities could be accurately reproduced with MB2 k-t (average ± twice the SD of the RMS error of 0.08 ± 0.22 cm/s and velocity peak reduction of 1.03% ± 6.47% compared with fully sampled velocities), whereas acceptable results were obtained with MB3 k-t (RMS error of 0.13 ± 0.58 cm/s and peak reduction of 2.21% ± 13.45%). When applied to tissue phase-mapping data, the proposed technique allowed three-directional velocity encoding to be simultaneously acquired at two/three slices in a single breath-hold of 18 heartbeats. No statistically significant differences were detected between MB2/MB3 k-t and single-band k-t motion traces averaged over the myocardium. Regional differences were found, however, when using the American Heart Association model for segmentation. CONCLUSION: An autocalibrated MB k-t acquisition/reconstruction framework is presented that allows three-directional velocity encoding of the myocardial velocities at multiple slices in one breath-hold.

Cardiac MRI Myocardial Functional and Tissue Characterization Detects Early Cardiac Dysfunction in a Mouse Model of Chemotherapy-Induced Cardiotoxicity.

BACKGROUND: Doxorubicin and doxorubicin-trastuzumab combination chemotherapy have been associated with cardiotoxicity that eventually leads to heart failure and may limit dose-effective cancer treatment. Current diagnostic strategies rely on decreased ejection fraction (EF) to diagnose cardiotoxicity. PURPOSE: The aim of this study is to explore the potential of cardiac MR (CMR) imaging to identify imaging biomarkers in a mouse model of chemotherapy-induced cardiotoxicity. METHODS: A cumulative dose of 25 mg/kg doxorubicin was administered over three weeks using subcutaneous pellets (n = 9, Dox). Another group (n = 9) received same dose of Dox and a total of 10 mg/kg trastuzumab (DT). Mice were imaged at baseline, 5/6 weeks and 10 weeks post-treatment on a 7T MRI system. The protocol included short-axis cine MRI covering the left ventricle (LV) and mid-ventricular short-axis tissue phase mapping (TPM), pre- and post-contrast T1 mapping, T2 mapping and Displacement Encoding with Stimulated Echoes (DENSE) strain encoded MRI. EF, peak myocardial velocities, native T1, T2, extracellular volume (ECV), and myocardial strain were quantified. N = 7 mice were sacrificed for histopathologic assessment of apoptosis at 5/6 weeks. RESULTS: Global peak systolic longitudinal velocity was reduced at 5/6 weeks in Dox (0.6 ± 0.3 vs 0.9 ± 0.3, p = 0.02). In the Dox group, native T1 was reduced at 5/6 weeks (1.3 ± 0.2 ms vs 1.6 ± 0.2 ms, p = 0.02), and relatively normalized at week 10 (1.4 ± 0.1 ms vs 1.6 ± 0.2 ms, p > 0.99). There was no change in EF and other MRI parameters and histopathologic results demonstrated minimal apoptosis in all mice (~1-2 apoptotic cell/high power field), suggesting early-stage cardiotoxicity. CONCLUSIONS: In a mouse model of chemotherapy-induced cardiotoxicity using doxorubicin and trastuzumab, advanced CMR shows promise in identifying treatment-related decrease in myocardial velocity and native T1 prior to the onset of cardiomyocyte apoptosis and reduction of EF.

Myocardial velocity, intra-, and interventricular dyssynchrony evaluated by tissue phase mapping in pediatric heart transplant recipients.

BACKGROUND: Endomyocardial biopsy (EMB) is the standard method for detecting allograft rejection in pediatric heart transplants (Htx). As EMB is invasive and carries a risk of complications, there is a need for a noninvasive alternative for allograft monitoring. PURPOSE: To quantify left and right ventricular (LV & RV) peak velocities, velocity twist, and intra-/interventricular dyssynchrony using tissue phase mapping (TPM) in pediatric Htx compared with controls, and to explore the relationship between global cardiac function parameters and the number of rejection episodes to these velocities and intra-/interventricular dyssynchrony. STUDY TYPE: Prospective. SUBJECTS: Twenty Htx patients (age: 16.0 ± 3.1 years, 11 males) and 18 age- and sex-matched controls (age: 15.5 ± 4.3 years, nine males). FIELD STRENGTH/SEQUENCE: 5T; 2D balanced cine steady-state free-precession (bSSFP), TPM (2D cine phase contrast with three-directional velocity encoding). ASSESSMENT: LV and RV circumferential, radial, and long-axis velocity-time curves, global and segmental peak velocities were measured using TPM. Short-axis bSSFP images were used to measure global LV and RV function parameters. STATISTICAL TESTS: A normality test (Lilliefors test) was performed on all data. For comparisons, a t-test was used for normally distributed data or a Wilcoxon rank-sum test otherwise. Correlations were determined by a Pearson correlation. RESULTS: Htx patients had significantly reduced LV (P < 0.05-0.001) and RV (P < 0.05-0.001) systolic and diastolic global and segmental long-axis velocities, reduced RV diastolic peak twist (P < 0.01), and presented with higher interventricular dyssynchrony for long-axis and circumferential motions (P < 0.05-0.001). LV diastolic long-axis dyssynchrony (r = 0.48, P = 0.03) and RV diastolic peak twist (r = -0.64, P = 0.004) significantly correlated with the total number of rejection episodes. DATA CONCLUSION: TPM detected differences in biventricular myocardial velocities in pediatric Htx patients compared with controls and indicated a relationship between Htx myocardial velocities and rejection history. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2020;51:1212-1222.

Evaluating Biventricular Myocardial Velocity and Interventricular Dyssynchrony in Adult Patients During the First Year After Heart Transplantation.

BACKGROUND: Magnetic resonance tissue phase mapping (TPM) measures three-directional myocardial velocities of the left and right ventricle (LV, RV). This noninvasive technique may supplement endomyocardial biopsy (EMB) in monitoring grafts post-heart transplantation (HTx). PURPOSE: To assess biventricular myocardial velocity alterations in grafts and investigate the relationship between velocities and acute cellular rejection (ACR) episodes. STUDY TYPE: Prospective. SUBJECTS: Twenty-seven patients within 1 year post-HTx (49 ± 13 years, 19 M) and 18 age-matched controls (49 ± 15 years, 12 M). FIELD STRENGTH/SEQUENCE: 1.5T, 2D balanced steady-state free precession, and TPM. ASSESSMENT: Ventricular function: end-diastolic and end-systolic volumes, stroke volumes, ejection fraction (EF), and myocardial mass. TPM velocities: peak-systolic and peak-diastolic velocities, cardiac twist, and interventricular dyssynchrony. ACR rejection episodes: International Society for Heart and Lung Transplantation grading of EMB specimens. STATISTICAL TESTS: The Lilliefors test for normality, unpaired t-tests, and Wilcoxon rank-sum tests for normally and nonnormally distributed data, respectively, were used, as well as multivariate regression for confounding variables and Pearson's correlation for associations between TPM velocities and global function. RESULTS: Compared to controls, HTx patients demonstrated reduced biventricular systolic longitudinal velocities (LV: 5.2 ± 2.1 vs. 4.0 ± 1.5 cm/s, P < 0.05; RV: 4.2 ± 1.3 vs. 3.1 ± 1.2 cm/s, P < 0.01). Correlation analysis revealed significant positive relationships for biventricular EF with radial peak velocities of the same ventricle in both systole and diastole (LV systole: r = 0.48, P < 0.01; LV diastole: r = 0.28, P < 0.05; RV systole: r = 0.35, P < 0.01; RV diastole: r = 0.36, P < 0.01). Segmentally, longitudinal velocities were impaired in 7/16 LV segments and 5/10 RV segments in systole and 7/10 RV segments in diastole. TPM analysis in studies with >4 preceding ACR episodes showed globally reduced RV and LV systolic radial velocity, and segmentally reduced radial and longitudinal systolic velocities. DATA CONCLUSION: Biventricular global and segmental velocities were reduced in HTx patients. Patients with >4 rejection episodes showed reduced myocardial velocities. The TPM sequence may add functional information for monitoring graft dysfunction. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2 J. Magn. Reson. Imaging 2020;52:920-929.

Altered regional myocardial velocities by tissue phase mapping and feature tracking in pediatric patients with hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is associated with heart failure, atrial fibrillation and sudden death. Reduced myocardial function has been reported in HCM despite normal left ventricular (LV) ejection fraction. Additionally, LV fibrosis is associated with elevated T1 and might be an outcome predictor. OBJECTIVE: To systematically compare tissue phase mapping and feature tracking for assessing regional LV function in children and young adults with HCM and pediatric controls, and to evaluate structure-function relationships among myocardial velocities, LV wall thickness and myocardial T1. MATERIALS AND METHODS: Seventeen pediatric patients with HCM and 21 age-matched controls underwent cardiac MRI including standard cine imaging, tissue phase mapping (two-dimensional cine phase contrast with three-directional velocity encoding), and modified Look-Locker inversion recovery to calculate native global LV T1. Maximum LV wall thickness was measured on cine images. LV radial, circumferential and long-axis myocardial velocity time courses, as well as global and segmental systolic and diastolic peak velocities, were quantified from tissue phase mapping and feature tracking. RESULTS: Both tissue phase mapping and feature tracking detected significantly decreased global and segmental diastolic radial and long-axis peak velocities (by 12-51%, P<0.001-0.05) in pediatric patients with HCM vs. controls. Feature tracking peak velocities were lower than directly measured tissue phase mapping velocities (mean bias = 0.3-2.9 cm/s). Diastolic global peak velocities correlated moderately with global T1 (r = -0.57 to -0.72, P<0.01) and maximum wall thickness (r = -0.37 to -0.61, P<0.05). CONCLUSION: Both tissue phase mapping and feature tracking detected myocardial velocity changes in children and young adults with HCM vs. controls. Associations between impaired diastolic LV velocities and elevated T1 indicate structure-function relationships in HCM.

Autocalibrated multiband CAIPIRINHA with through-time encoding: Proof of principle and application to cardiac tissue phase mapping.

PURPOSE: In conventional multiband (MB) CAIPIRINHA, additional reference scans are acquired to allow the separation of the excited slices. In this study, an acquisition-reconstruction technique that makes use of the MB data to calculate these reference data is presented. The method was integrated into a 2D time-resolved phase-contrast MR sequence used to assess velocities of the myocardium. METHODS: The RF phases of the MB pulse are cycled through time so that consecutive cardiac phases can be grouped to form reference scans at a lower temporal resolution. These reference data are subsequently used to separate the original slices at the original, high temporal resolution using slice/split-slice GRAPPA algorithms. Slice separation performances are evaluated and compared with conventional methods at 3 T, and 3 different strategies for the calibration of the kernels are proposed and compared. Finally, 6 subjects were scanned to assess velocities of the myocardium. RESULTS: Because the acquisition of external references is not needed, no additional breath-holds are required and the full MB acceleration could be exploited. Because the reference and MB data have the same resolution and phase structure, better slice separation was achieved when comparing the proposed technique to conventional workflows. Finally, time-resolved velocities of the myocardial tissue were successfully quantified from MB data, showing good agreement with single-band measurements. CONCLUSION: Our built-in reference method allows the full exploitation of the MB acceleration and it limits the number of breath-holds.

Comprehensive MR Analysis of Cardiac Function, Aortic Hemodynamics and Left Ventricular Strain in Pediatric Cohort with Isolated Bicuspid Aortic Valve.

Bicuspid aortic valve (BAV) disease demonstrates a range of clinical presentations and complications. We aim to use cardiac MRI (CMR) to evaluate left ventricular (LV) parameters, myocardial strain and aortic hemodynamics in pediatric BAV patients with and without aortic stenosis (AS) or regurgitation (AR) compared to tricuspid aortic valve (TAV) controls. We identified 58 pediatric BAV patients without additional cardiovascular pathology and 25 healthy TAV controls (15.3 ± 2.2 years) who underwent CMR with 4D flow. BAV cohort included subgroups with no valvulopathy (n = 13, 14.3 ± 4.7 years), isolated AS (n = 19, 14.5 ± 4.0 years), mixed valve disease (AS + AR) (n = 13, 17.1 ± 3.2 years), and prior valvotomy/valvuloplasty (n = 13, 13.9 ± 3.2 years). CMR data included LV volumetric and mass indices, myocardial strain and aortic hemodynamics. BAV patients with no valvulopathy or isolated AS had similar LV parameters to controls excepting cardiac output (p < 0.05). AS + AR and post-surgical patients had abnormal LV volumetric and mass indices (p < 0.01). Post-surgical patients had decreased global longitudinal strain (p = 0.02); other subgroups had comparable strain to controls. Patients with valvulopathy demonstrated elevated velocity and wall shear stress (WSS) in the ascending aorta (AAo) and arch (p < 0.01), while those without valve dysfunction had only elevated AAo velocity (p = 0.03). Across the cohort, elevated AAo velocity and WSS correlated to higher LV mass (p < 0.01), and abnormal hemodynamics correlated to decreased strain rates (p < 0.045). Pediatric BAV patients demonstrate abnormalities in LV parameters as a function of valvular dysfunction, most significantly in children with AS + AR or prior valvotomy/valvuloplasty. Correlations between aortic hemodynamics, LV mass and strain suggest valvular dysfunction could drive LV remodeling. Multiparametric CMR assessment in pediatric BAV may help stratify risk for cardiac remodeling and dysfunction.

The larmor frequency shift in magnetically heterogeneous media depends on their mesoscopic structure.

PURPOSE: Recent studies have addressed the determination of the NMR precession frequency in biological tissues containing magnetic susceptibility differences between cell types. The purpose of this study is to investigate the dependence of the precession frequency on medium microstructure using a simple physical model. THEORY: This dependence is governed by diffusion of NMR-visible molecules in magnetically heterogeneous microenvironments. In the limit of fast diffusion, the precession frequency is determined by the average susceptibility-induced magnetic field, whereas in the limit of slow diffusion it is determined by the average local phase factor of precessing spins. METHODS: The main method used is Monte Carlo simulation of isotropic suspensions of impermeable magnetized spheres. In addition, NMR spectroscopy was performed in aqueous suspensions of polystyrene microbeads. RESULTS: The precession frequency depends on the structural organization of magnetized objects in the medium. Monte Carlo simulations demonstrated a nonmonotonic transition between the regimes of fast and slow diffusion. NMR experiments confirmed the transition, but were unable to confirm its precise form. Results for a given pattern of structural organization obey a scaling law. CONCLUSION: The NMR precession frequency exhibits a complex dependence on medium structure. Our results suggest that the commonly assumed limit of fast water diffusion holds for biological tissues with small cells. Magn Reson Med 79:1101-1110, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Observation of magnetic structural universality and jamming transition with NMR.

Nuclear magnetic resonance (NMR) has been instrumental in deciphering the structure of proteins. Here we show that transverse NMR relaxation, through its time-dependent relaxation rate, is distinctly sensitive to the structure of complex materials or biological tissues at the mesoscopic scale, from micrometers to tens of micrometers. Based on the ideas of universality, we show analytically and numerically that the time-dependent transverse relaxation rate approaches its long-time limit in a power-law fashion, with the dynamical exponent reflecting the universality class of mesoscopic magnetic structure. The spectral line shape acquires the corresponding non-analytic power law singularity at zero frequency. We experimentally detect the change in the dynamical exponent as a result of the transition into maximally random jammed state characterized by hyperuniform correlations. The relation between relaxational dynamics and magnetic structure opens the way for noninvasive characterization of porous media, complex materials and biological tissues.

Cardiac Magnetic Resonance Strain in Beta Thalassemia Major Correlates with Cardiac Iron Overload.

BACKGROUND: Beta thalassemia major (Beta-TM) is an inherited condition which presents at around two years of life. Patients with Beta-;TM may develop cardiac iron toxicity secondary to transfusion dependence. Cardiovascular magnetic resonance (CMR) T2*, a technique designed to quantify myocardial iron deposition, is a driving component of disease management. A decreased T2* value represents increasing cardiac iron overload. The clinical manifestation is a decline in ejection fraction (EF). However, there may be early subclinical changes in cardiac function that are not detected by changes in EF. CMR-derived strain assesses myocardial dysfunction prior to decline in EF. Our primary aim was to assess the correlation between CMR strain and T2* in the Beta-TM population. METHODS: Circumferential and longitudinal strain was analyzed. Pearson's correlation was calculated for T2* values and strain in the Beta-TM population. RESULTS: We identified 49 patients and 18 controls. Patients with severe disease (low T2*) were found to have decreased global circumferential strain (GCS) in comparison to other T2* groups. A correlation was identified between GCS and T2* (r = 0.5; p < 0.01). CONCLUSION: CMR-derived strain can be a clinically useful tool to predict early myocardial dysfunction in Beta-TM.

Larmor frequency dependence on structural anisotropy of magnetically heterogeneous media.

The effect of anisotropic magnetic microstructure on the measurable Larmor frequency offset is investigated in media with heterogeneous magnetic susceptibility using Monte Carlo simulations. The focus is on the transition between the regimes of fast and slow diffusion of NMR-reporting molecules. Simulations demonstrate a perfect agreement with the previously developed analytic theory for fast diffusion. Beyond this regime, the frequency offset shows a pronounced dependence on the medium microarchitecture and the diffusivity of NMR-reporting spins in relation to the magnitude of the susceptibility-induced magnetic field.

Impact of age and cardiac disease on regional left and right ventricular myocardial motion in healthy controls and patients with repaired tetralogy of fallot.

The assessment of both left (LV) and right ventricular (RV) motion is important to understand the impact of heart disease on cardiac function. The MRI technique of tissue phase mapping (TPM) allows for the quantification of regional biventricular three-directional myocardial velocities. The goal of this study was to establish normal LV and RV velocity parameters across a wide range of pediatric to adult ages and to investigate the feasibility of TPM for detecting impaired regional biventricular function in patients with repaired tetralogy of Fallot (TOF). Thirty-six healthy controls (age = 1-75 years) and 12 TOF patients (age = 5-23 years) underwent cardiac MRI including TPM in short-axis locations (base, mid, apex). For ten adults, a second TPM scan was used to assess test-retest reproducibility. Data analysis included the calculation of biventricular radial, circumferential, and long-axis velocity components, quantification of systolic and diastolic peak velocities in an extended 16 + 10 LV + RV segment model, and assessment of inter-ventricular dyssynchrony. Biventricular velocities showed good test-retest reproducibility (mean bias ≤ 0.23 cm/s). Diastolic radial and long-axis peak velocities for LV and RV were significantly reduced in adults compared to children (19-61%, p < 0.001-0.02). In TOF patients, TPM identified significantly reduced systolic and diastolic LV and RV long-axis peak velocities (20-50%, p < 0.001-0.05) compared to age-matched controls. In conclusion, tissue phase mapping enables comprehensive analysis of global and regional biventricular myocardial motion. Changes in myocardial velocities associated with age underline the importance of age-matched controls. This pilot study in TOF patients shows the feasibility to detect regionally abnormal LV and RV motion.