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Level Of Evidence: 5 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:319-320. [ABSTRACT FROM AUTHOR]

Intracardiac blood flow patterns are affected by the morphology of cardiac structures and are set up to support the heart's pump function. Exercise affects contractility and chamber size as well as pre‐ and afterload. The aim of this study was to test the feasibility of four‐dimensional phase contrast cardiovascular MRI under pharmacological stress and to study left ventricular blood flow under stress. 4D flow data were successfully acquired and analysed in 12 animals. During dobutamine infusion, heart rate and ejection fraction increased (82 ± 5 bpm versus 124 ± 3 bpm/46 ± 9% versus 65 ± 7%; both p < 0.05). A decrease in left ventricular end‐diastolic volume (72 ± 14 mL versus 55 ± 8 mL; p < 0.05) and end‐systolic volume (40 ± 15 mL versus 19 ± 6 mL; p < 0.05) but no change in stroke volume were observed. Trans‐mitral diastolic inflow velocity increased under dobutamine and the trajectory of inflowing blood was directed towards the anterior septum with increased inflow angle (26 ± 5°) when compared with controls (15 ± 2°). In 5/6 animals undergoing stress diastolic vortices developed later, and in 3/6 animals vortices collapsed earlier with significantly smaller cross‐sectional area during diastole. The vorticity index was not affected. Under the stress condition direct flow (% ejection within the next heart beat) increased from 43 ± 6% to 53 ± 8%. 4D MRI blood flow acquisition and analysis are feasible in pig hearts under dobutamine‐induced stress. Flow patterns characterized by high blood velocity and antero‐septally oriented diastolic inflow as well as decreased ventricular volumes are unfavourable conditions for diastolic vortex development under pharmacological stress, and cardiac output is increased by a rise in heart rate and directly ejected left ventricular blood volume. In this study the feasibility of 4D flow MRI during dobutamine‐induced stress was assessed, and changes in intraventricular blood flow patterns are reported for the porcine heart. A decrease in cardiac volume, antero‐septally oriented diastolic inflow and high velocity flow was found, providing unfavorable conditions for diastolic vortex development compared with the rest condition. [ABSTRACT FROM AUTHOR]

Background: The feasibility of absolute myocardial blood flow quantification and suitability of hyperpolarized [1-13C] pyruvate as contrast agent for first-pass cardiovascular magnetic resonance (CMR) perfusion measurements are investigated with simulations and demonstrated in vivo in a swine model. Methods: A versatile simulation framework for hyperpolarized CMR subject to physical, physiological and technical constraints was developed and applied to investigate experimental conditions for accurate perfusion CMR with hyperpolarized [1-13C] pyruvate. Absolute and semi-quantitative perfusion indices were analyzed with respect to experimental parameter variations and different signal-to-noise ratio (SNR) levels. Absolute myocardial blood flow quantification was implemented with an iterative deconvolution approach based on Fermi functions. To demonstrate in vivo feasibility, velocity-selective excitation with an echo-planar imaging readout was used to acquire dynamic myocardial stress perfusion images in four healthy swine. Arterial input functions were extracted from an additional image slice with conventional excitation that was acquired within the same heartbeat. Results: Simulations suggest that obtainable SNR and B0 inhomogeneity in vivo are sufficient for the determination of absolute and semi-quantitative perfusion with ≤25% error. It is shown that for expected metabolic conversion rates, metabolic conversion of pyruvate can be neglected over the short duration of acquisition in first-pass perfusion CMR. In vivo measurements suggest that absolute myocardial blood flow quantification using hyperpolarized [1-13C] pyruvate is feasible with an intra-myocardial variability comparable to semi-quantitative perfusion indices. Conclusion: The feasibility of quantitative hyperpolarized first-pass perfusion CMR using [1-13C] pyruvate has been investigated in simulations and demonstrated in swine. Using an approved and metabolically active compound is envisioned to increase the value of hyperpolarized perfusion CMR in patients. [ABSTRACT FROM AUTHOR]

Aims: Myocardial involvement is common in patients with systemic sclerosis (SSc) and causes myocardial fibrosis and subtle ventricular dysfunction. However, the temporal onset of myocardial involvement during the progression of the disease and its prognostic value are yet unknown. We used cardiovascular magnetic resonance (CMR) to investigate subclinical functional impairment and diffuse myocardial fibrosis in patients with very early diagnosis of SSc (VEDOSS) and established SSc and examined whether this was associated with mortality., Methods and Results: One hundred and ten SSc patients (86 established SSc, 24 VEDOSS) and 15 healthy controls were prospectively recruited. The patients were followed-up for a median duration of 7.0 years (interquartile range 6.0-7.3 years). Study subjects underwent CMR including assessment of myocardial fibrosis [native T1 and extracellular volume (ECV)] and measurement of global longitudinal (GLS) and circumferential (GCS) myocardial strain. Native T1 values and ECV were elevated in VEDOSS and SSc patients compared with controls (P < 0.001). GLS was similar in VEDOSS and controls but significantly impaired in patients with established SSc (P < 0.001). GCS was similar over all groups (P = 0.88). There were 12 deaths during follow-up. Elevated native T1 [hazard ratio (HR) 5.8, 95% confidence interval (CI): 1.7-20.4; P = 0.006] and reduced GLS (HR 6.1, 95% CI: 1.3-29.9; P = 0.038) identified subjects with increased risk of death. Only native T1 was predictive for cardiovascular mortality (P < 0.001)., Conclusion: Subclinical myocardial involvement first manifests as diffuse myocardial fibrosis identified by the expansion of ECV and increased native T1 in VEDOSS patients while subtle functional impairment only occurs in established SSc. Native T1 and GLS have prognostic value for all-cause mortality in SSc patients., Competing Interests: Conflict of interest: B.M. has/had grant/research support from Abbvie, Protagen, Novartis Biomedical Research, received speaker fees from Böhringer Ingelheim as well as congress support from Pfizer, Roche, Actelion, Mepha, and MSD. C.M. has received congress support from Actelion and Roche, and personal fees from Boehringer-Ingelheim, Mepha, and MEDtalks Switzerland, outside the submitted work. R.D. reports grants/research support from Pfizer, Actelion, and personal fees (speaker/consultancy) from Actelion and Boehringer-Ingelheim, outside the submitted work. O.D. has/had consultancy relationship with and/or has received research funding from or has served as a speaker for the following companies in the area of potential treatments for systemic sclerosis and its complications in the last 3 years: Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, AstraZeneca, Baecon, Blade, Bayer, Boehringer-Ingelheim, ChemomAb, Corbus, CSL Behring, Galapagos, Glenmark, GSK, Horizon (Curzion), Inventiva, iQvia, Kymera, Lupin, Medac, Medscape, Miltenyi Biotec, Mitsubishi Tanabe, Novartis, Prometheus, Roche, Roivant, Sanofi, Serodapharm, Topadur and UCB. Patent issued ‘mir-29 for the treatment of systemic sclerosis’ (US8247389, EP2331143). O.D. and B.M. have a patent for ‘mir-29 for the treatment of systemic sclerosis’ (US8247389, EP2331143). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: We examined the dynamic response of the myocardium to infarction in a longitudinal porcine study using relaxometry, functional as well as diffusion cardiovascular magnetic resonance (CMR). We sought to compare non contrast CMR methods like relaxometry and in-vivo diffusion to contrast enhanced imaging and investigate the link of microstructural and functional changes in the acute and chronically infarcted heart., Methods: CMR was performed on five myocardial infarction pigs and four healthy controls. In the infarction group, measurements were obtained 2 weeks before 90 min occlusion of the left circumflex artery, 6 days after ischemia and at 5 as well as 9 weeks as chronic follow-up. The timing of measurements was replicated in the control cohort. Imaging consisted of functional cine imaging, 3D tagging, T2 mapping, native as well as gadolinium enhanced T1 mapping, cardiac diffusion tensor imaging, and late gadolinium enhancement imaging., Results: Native T1, extracellular volume (ECV) and mean diffusivity (MD) were significantly elevated in the infarcted region while fractional anisotropy (FA) was significantly reduced. During the transition from acute to chronic stages, native T1 presented minor changes (< 3%). ECV as well as MD increased from acute to the chronic stages compared to baseline: ECV: 125 ± 24% (day 6) 157 ± 24% (week 5) 146 ± 60% (week 9), MD: 17 ± 7% (day 6) 33 ± 14% (week 5) 29 ± 15% (week 9) and FA was further reduced: - 31 ± 10% (day 6) - 38 ± 8% (week 5) - 36 ± 14% (week 9). T2 as marker for myocardial edema was significantly increased in the ischemic area only during the acute stage (83 ± 3 ms infarction vs. 58 ± 2 ms control p < 0.001 and 61 ± 2 ms in the remote area p < 0.001). The analysis of functional imaging revealed reduced left ventricular ejection fraction, global longitudinal strain and torsion in the infarct group. At the same time the transmural helix angle (HA) gradient was steeper in the chronic follow-up and a correlation between longitudinal strain and transmural HA gradient was detected (r = 0.59 with p < 0.05). Comparing non-gadolinium enhanced data T2 mapping showed the largest relative change between infarct and remote during the acute stage (+ 33 ± 4% day 6, with p = 0.013 T2 vs. MD, p = 0.009 T2 vs. FA and p = 0.01 T2 vs. T1) while FA exhibited the largest relative change between infarct and remote during the chronic follow-up (+ 31 ± 2% week 5, with p = N.S. FA vs. MD, p = 0.03 FA vs. T2 and p = 0.003 FA vs. T1). Overall, diffusion parameters provided a higher contrast (> 23% for MD and > 27% for FA) during follow-up compared to relaxometry (T1 17-18%/T2 10-20%)., Conclusion: During chronic follow-up after myocardial infarction, cardiac diffusion tensor imaging provides a higher sensitivity for mapping microstructural alterations when compared to non-contrast enhanced relaxometry with the added benefit of providing directional tensor information to assess remodelling of myocyte aggregate orientations, which cannot be otherwise assessed., (© 2021. The Author(s).)

A major concern in personalised models of heart mechanics is the unknown zero-pressure domain, a prerequisite for accurately predicting cardiac biomechanics. As the reference configuration cannot be captured by clinical data, studies often employ in-vivo frames which are unlikely to correspond to unloaded geometries. Alternatively, zero-pressure domain is approximated through inverse methodologies, which, however, entail assumptions pertaining to boundary conditions and material parameters. Both approaches are likely to introduce biases in estimated biomechanical properties; nevertheless, quantification of these effects is unattainable without ground-truth data. In this work, we assess the unloaded state influence on model-derived biomechanics, by employing an in-silico modelling framework relying on experimental data on porcine hearts. In-vivo images are used for model personalisation, while in-situ experiments provide a reliable approximation of the reference domain, creating a unique opportunity for a validation study. Personalised whole-cycle cardiac models are developed which employ different reference domains (image-derived, inversely estimated) and are compared against ground-truth model outcomes. Simulations are conducted with varying boundary conditions, to investigate the effect of data-derived constraints on model accuracy. Attention is given to modelling the influence of the ribcage on the epicardium, due to its close proximity to the heart in the porcine anatomy. Our results find merit in both approaches for dealing with the unknown reference domain, but also demonstrate differences in estimated biomechanical quantities such as material parameters, strains and stresses. Notably, they highlight the importance of a boundary condition accounting for the constraining influence of the ribcage, in forward and inverse biomechanical models., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Cardiac diffusion tensor imaging using EPI readout is prone to image distortions in the presence of field inhomogeneities. In this work, a framework to analyze and correct image distortions in cardiac diffusion tensor imaging is presented., Methods: A multi-coil reconstruction framework was implemented to enable field map-based off-resonance correction. Numerical simulations were used to examine reconstruction performance for EPI phase-encode directions blip up-down and down-up for different degrees of off-resonance gradients and varying field map resolution. The impact of coil encoding was analyzed using the g-factor and normalized RMSE. Finally, the proposed method was tested on free-breathing in vivo cardiac diffusion tensor imaging data acquired in healthy subjects at 3 Tesla., Results: Depending on the local field map gradient strength and polarity and the selected phase-encode direction, field inhomogeneities lead to either local spatial compression or stretching with standard image reconstruction. Although spatial compression results in loss of image resolution upon field map-based reconstruction, spatial stretching can be recovered once multiple receive coils are utilized. Multi-coil reconstruction was found to reduce the normalized RMSE from 34.3% to 8.1% for image compression, and 33.6% to 1.8% for image stretching, with resulting average g-factors 14.7 ± 2.9 and 1.2 ± 0.1, respectively. In vivo, multi-coil field map-based reconstruction yielded improved alignment of angle maps with anatomical cine data., Conclusion: Multi-coil, field map-based image reconstruction for echo-planar cardiac diffusion tensor imaging allows accurate image reconstruction provided that the phase-encode direction and polarity is chosen to principally align with the direction and polarity of the prominent gradients of field inhomogeneities., (© 2020 International Society for Magnetic Resonance in Medicine.)

Background: In-vivo cardiovascular magnetic resonance (CMR) diffusion tensor imaging (DTI) allows imaging of alterations of cardiac fiber architecture in diseased hearts. Cardiac amyloidosis (CA) causes myocardial infiltration of misfolded proteins with unknown consequences for myocardial microstructure. This study applied CMR DTI in CA to assess microstructural alterations and their consequences for myocardial function compared to healthy controls., Methods: Ten patients with CA (8 AL, 2 ATTR) and ten healthy controls were studied using a diffusion-weighed second-order motion-compensated spin-echo sequence at 1.5 T. Additionally, left ventricular morphology, ejection fraction, strain and native T1 values were obtained in all subjects. In CA patients, T1 mapping was repeated after the administration of gadolinium for extracellular volume fraction (ECV) calculation. CMR DTI analysis was performed to yield the scalar diffusion metrics mean diffusivity (MD) and fractional anisotropy (FA) as well as the characteristics of myofiber orientation including helix, transverse and E2A sheet angle (HA, TA, E2A)., Results: MD and FA were found to be significantly different between CA patients and healthy controls (MD 1.77 ± 0.17 10 - 3 vs 1.41 ± 0.07 10 - 3  mm 2 /s, p <  0.001; FA 0.25 ± 0.04 vs 0.35 ± 0.03, p <  0.001). MD demonstrated an excellent correlation with native T1 (r = 0.908, p <  0.001) while FA showed a significant correlation with ECV in the CA population (r = - 0.851, p <  0.002). HA exhibited a more circumferential orientation of myofibers in CA patients, in conjunction with a higher TA standard deviation and a higher absolute E2A sheet angle. The transmural HA slope was found to be strongly correlated with the global longitudinal strain (r = 0.921, p < 0.001)., Conclusion: CMR DTI reveals significant alterations of scalar diffusion metrics in CA patients versus healthy controls. Elevated MD and lower FA values indicate myocardial disarray with higher diffusion in CA that correlates well with native T1 and ECV measures. In CA patients, CMR DTI showed pronounced circumferential orientation of the myofibers, which may provide the rationale for the reduction of global longitudinal strain that occurs in amyloidosis patients. Accordingly, CMR DTI captures specific features of amyloid infiltration, which provides a deeper understanding of the microstructural consequences of CA.

Background: The feasibility of absolute myocardial blood flow quantification and suitability of hyperpolarized [1- 13 C] pyruvate as contrast agent for first-pass cardiovascular magnetic resonance (CMR) perfusion measurements are investigated with simulations and demonstrated in vivo in a swine model., Methods: A versatile simulation framework for hyperpolarized CMR subject to physical, physiological and technical constraints was developed and applied to investigate experimental conditions for accurate perfusion CMR with hyperpolarized [1- 13 C] pyruvate. Absolute and semi-quantitative perfusion indices were analyzed with respect to experimental parameter variations and different signal-to-noise ratio (SNR) levels. Absolute myocardial blood flow quantification was implemented with an iterative deconvolution approach based on Fermi functions. To demonstrate in vivo feasibility, velocity-selective excitation with an echo-planar imaging readout was used to acquire dynamic myocardial stress perfusion images in four healthy swine. Arterial input functions were extracted from an additional image slice with conventional excitation that was acquired within the same heartbeat., Results: Simulations suggest that obtainable SNR and B 0 inhomogeneity in vivo are sufficient for the determination of absolute and semi-quantitative perfusion with ≤25% error. It is shown that for expected metabolic conversion rates, metabolic conversion of pyruvate can be neglected over the short duration of acquisition in first-pass perfusion CMR. In vivo measurements suggest that absolute myocardial blood flow quantification using hyperpolarized [1- 13 C] pyruvate is feasible with an intra-myocardial variability comparable to semi-quantitative perfusion indices., Conclusion: The feasibility of quantitative hyperpolarized first-pass perfusion CMR using [1- 13 C] pyruvate has been investigated in simulations and demonstrated in swine. Using an approved and metabolically active compound is envisioned to increase the value of hyperpolarized perfusion CMR in patients.

We propose an estimation scheme for local fiber bundle direction in the left ventricle directly from gray values of arbitrarily spaced cardiac diffusion weighted images (DWI). The approach is based on a parametric and space-dependent mathematical representation of the myocardial fiber bundle orientation and hence the diffusion tensor (DT) for the ventricular geometry. By solving a nonlinear inverse problem derived from a maximum likelihood estimator, the degrees of freedom of the fiber and DT model can be estimated from the measured gray values of the DWIs. The continuity of the DT model allows to relax the restriction to the individual DWIs to match spatially like for voxelwise DT calculation. Hence, the spatial misalignment between image slices with different diffusion encoding directions, that is encountered in-vivo cardiac imaging practice can be integrated into the estimation scheme. This feature results then in a negligible impact of the spatial misalignment on the reconstructed solution. We illustrate the methodology using synthetic data and compare it against a previously reported fiber bundle reconstruction technique. To show the potential for real data, we also present results for multi-slice data constructed from ex-vivo cardiac diffusion weighted measurements in both mono- and bi-ventricular configurations., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: A velocity-selective binomial excitation scheme for myocardial first-pass perfusion measurements with hyperpolarized 13 C substrates, which preserves bolus magnetization inside the blood pool, is presented. The proposed method is evaluated against gadolinium-enhanced 1 H measurements in-vivo., Methods: The proposed excitation with an echo-planar imaging readout was implemented on a clinical CMR system. Dynamic myocardial stress perfusion images were acquired in six healthy pigs after bolus injection of hyperpolarized 13 C urea with the velocity-selective vs. conventional excitation, as well as standard 1 H gadolinium-enhanced images. Signal-to-noise, contrast-to-noise (CNR) and homogeneity of semi-quantitative perfusion measures were compared between methods based on first-pass signal-intensity time curves extracted from a mid-ventricular slice. Diagnostic feasibility is demonstrated in a case of septal infarction., Results: Velocity-selective excitation provides over three-fold reduction in blood pool signal with a two-fold increase in myocardial CNR. Extracted first-pass perfusion curves reveal a significantly reduced variability of semi-quantitative first-pass perfusion measures (12-20%) for velocity-selective excitation compared to conventional excitation (28-93%), comparable to that of reference 1 H gadolinium data (9-15%). Overall image quality appears comparable between the velocity-selective hyperpolarized and gadolinium-enhanced imaging., Conclusion: The feasibility of hyperpolarized 13 C first-pass perfusion CMR has been demonstrated in swine. Comparison with reference 1 H gadolinium data revealed sufficient data quality and indicates the potential of hyperpolarized perfusion imaging for human applications.

Fractional anisotropy (FA) obtained by diffusion tensor imaging (DTI) can be used to image the kidneys without any contrast media. FA of the medulla has been shown to correlate with kidney function. It is expected that higher spatial resolution would improve the depiction of small structures within the kidney. However, the achievement of high spatial resolution in renal DTI remains challenging as a result of respiratory motion and susceptibility to diffusion imaging artefacts. In this study, a targeted field of view (TFOV) method was used to obtain high-resolution FA maps and colour-coded diffusion tensor orientations, together with measures of the medullary and cortical FA, in 12 healthy subjects. Subjects were scanned with two implementations (dual and single kidney) of a TFOV DTI method. DTI scans were performed during free breathing with a navigator-triggered sequence. Results showed high consistency in the greyscale FA, colour-coded FA and diffusion tensors across subjects and between dual- and single-kidney scans, which have in-plane voxel sizes of 2 × 2 mm(2) and 1.2 × 1.2 mm(2) , respectively. The ability to acquire multiple contiguous slices allowed the medulla and cortical FA to be quantified over the entire kidney volume. The mean medulla and cortical FA values were 0.38 ± 0.017 and 0.21 ± 0.019, respectively, for the dual-kidney scan, and 0.35 ± 0.032 and 0.20 ± 0.014, respectively, for the single-kidney scan. The mean FA between the medulla and cortex was significantly different (p < 0.001) for both dual- and single-kidney implementations. High-spatial-resolution DTI shows promise for improving the characterization and non-invasive assessment of kidney function., (© 2014 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd.)

Purpose: In this work we present a dual-phase diffusion tensor imaging (DTI) technique that incorporates a correction scheme for the cardiac material strain, based on 3D myocardial tagging., Methods: In vivo dual-phase cardiac DTI with a stimulated echo approach and 3D tagging was performed in 10 healthy volunteers. The time course of material strain was estimated from the tagging data and used to correct for strain effects in the diffusion weighted acquisition. Mean diffusivity, fractional anisotropy, helix, transverse and sheet angles were calculated and compared between systole and diastole, with and without strain correction. Data acquired at the systolic sweet spot, where the effects of strain are eliminated, served as a reference., Results: The impact of strain correction on helix angle was small. However, large differences were observed in the transverse and sheet angle values, with and without strain correction. The standard deviation of systolic transverse angles was significantly reduced from 35.9±3.9° to 27.8°±3.5° (p<0.001) upon strain-correction indicating more coherent fiber tracks after correction. Myocyte aggregate structure was aligned more longitudinally in systole compared to diastole as reflected by an increased transmural range of helix angles (71.8°±3.9° systole vs. 55.6°±5.6°, p<0.001 diastole). While diastolic sheet angle histograms had dominant counts at high sheet angle values, systolic histograms showed lower sheet angle values indicating a reorientation of myocyte sheets during contraction., Conclusion: An approach for dual-phase cardiac DTI with correction for material strain has been successfully implemented. This technique allows assessing dynamic changes in myofiber architecture between systole and diastole, and emphasizes the need for strain correction when sheet architecture in the heart is imaged with a stimulated echo approach.

In this paper, we propose a novel 3D sine wave modeling (3D SinMod) approach to automatic analysis of 3D cardiac deformations. An accelerated 3D complementary spatial modulation of magnetization (CSPAMM) tagging technique was used to modulate the myocardial tissue and to acquire 3D MR data sets of the whole-heart including three orthog- onal tags within three breath-holds. Each tag set is able to assess the motion along a direction perpendicular to the tag lines. With the application of CSPAMM, the effect of tag fading encountered in SPAMM tagging due to T1 relaxation is mitigated and tag deformations can be visualized for the entire cardiac cycle, including diastolic phases. In the proposed approach, the environment around each voxel in the 3D volume is modeled as a moving sine wavefront with local frequency and amplitude. The biggest advantage of the proposed technique is that the entire framework, from data acquisition to data analysis is in the 3D domain, which permits quantification of both the in-plane and through-plane motion components. The accuracy and the effectiveness of the proposed method has been validated using both simulated and in vivo tag data.