Cardiac function in a large animal model of myocardial infarction at 7 T: deep learning based automatic segmentation increases reproducibility.

Cardiac magnetic resonance (CMR) imaging allows precise non-invasive quantification of cardiac function. It requires reliable image segmentation for myocardial tissue. Clinically used software usually offers automatic approaches for this step. These are, however, designed for segmentation of human images obtained at clinical field strengths. They reach their limits when applied to preclinical data and ultrahigh field strength (such as CMR of pigs at 7 T). In our study, eleven animals (seven with myocardial infarction) underwent four CMR scans each. Short-axis cine stacks were acquired and used for functional cardiac analysis. End-systolic and end-diastolic images were labelled manually by two observers and inter- and intra-observer variability were assessed. Aiming to make the functional analysis faster and more reproducible, an established deep learning (DL) model for myocardial segmentation in humans was re-trained using our preclinical 7 T data (n = 772 images and labels). We then tested the model on n = 288 images. Excellent agreement in parameters of cardiac function was found between manual and DL segmentation: For ejection fraction (EF) we achieved a Pearson's r of 0.95, an Intraclass correlation coefficient (ICC) of 0.97, and a Coefficient of variability (CoV) of 6.6%. Dice scores were 0.88 for the left ventricle and 0.84 for the myocardium.

Characterization of anthracycline-induced cardiotoxicity by diffusion tensor magnetic resonance imaging.

Anthracyclines are highly potent anti-cancer drugs, but their clinical use is limited by severe cardiotoxic side effects. The impact of anthracycline-induced cardiotoxicity (AIC) on left ventricular (LV) microarchitecture and diffusion properties remains unknown. This study sought to characterize AIC by cardiovascular magnetic resonance diffusion tensor imaging (DTI). Mice were treated with Doxorubicin (DOX; n = 16) for induction of AIC or saline as corresponding control (n = 15). Cardiac function was assessed via echocardiography at the end of the study period. Whole hearts (n = 8 per group) were scanned ex vivo by high-resolution DTI at 7 T. Results were correlated with histopathology and mass spectrometry imaging. Mice with AIC demonstrated systolic dysfunction (LVEF 52 ± 3% vs. 43 ± 6%, P < 0.001), impaired global longitudinal strain (-19.6 ± 2.0% vs. -16.6 ± 3.0%, P < 0.01), and cardiac atrophy (LV mass index [mg/mm], 4.3 ± 0.1 vs. 3.6 ± 0.2, P < 0.01). Regional sheetlet angles were significantly lower in AIC, whereas helix angle and relative helicity remained unchanged. In AIC, fractional anisotropy was increased (0.12 ± 0.01 vs. 0.14 ± 0.02, P < 0.05). DOX-treated mice displayed higher planar and less spherical anisotropy (CPlanar 0.07 ± 0.01 vs. 0.09 ± 0.01, P < 0.01; CSpherical 0.89 ± 0.01 vs. 0.87 ± 0.02, P < 0.05). CPlanar and CSpherical yielded good discriminatory power to distinguish between mice with and without AIC (c-index 0.91 and 0.84, respectively, P for both < 0.05). AIC is associated with regional changes in sheetlet angle but no major abnormalities of global LV microarchitecture. The geometric shape of the diffusion tensor is altered in AIC. DTI may provide a new tool for myocardial characterization in patients with AIC, which warrants future clinical studies to evaluate its diagnostic utility.

Cardiovascular Molecular Imaging With Fluorine-19 MRI: The Road to the Clinic.

Fluorine-19 (19F) magnetic resonance imaging is a unique quantitative molecular imaging modality that makes use of an injectable fluorine-containing tracer that generates the only visible 19F signal in the body. This hot spot imaging technique has recently been used to characterize a wide array of cardiovascular diseases and seen a broad range of technical improvements. Concurrently, its potential to be translated to the clinical setting is being explored. This review provides an overview of this emerging field and demonstrates its diagnostic potential, which shows promise for clinical translation. We will describe 19F magnetic resonance imaging hardware, pulse sequences, and tracers, followed by an overview of cardiovascular applications. Finally, the challenges on the road to clinical translation are discussed.

Complementary analysis of specific absorption rate safety for an 8Tx/16Rx array with central symmetry of elements for magnetic resonance imaging of the human heart and abdominopelvic organs at 7 T.

A complementary safety assessment of the specific absorption rate (SAR) of the electromagnetic energy was performed in a prototype 8Tx/16Rx RF array for cardiac magnetic resonance imaging (MRI) at 7 T. The study aimed to address two critical aspects of 7-T SAR safety not always explicitly examined by coil vendors: (i) the influence of an RF-array position on a peak SAR value, and (ii) the risk of exceeding the permitted maximal SAR in the tissue surrounding conductive passive implants. The full-wave 3D electromagnetic simulations for the thorax with shifted array position and the whole-body volume in the presence of a dental retainer, an intrauterine contraceptive device (IUD), and a hip joint implant, were performed for two human voxel models. The effect of the array displacement on the SAR was simulated for seven array locations on the thorax shifted from the central position in different directions on 50 mm. The peak SAR values for both models were analyzed for the three phase-only transmit vectors optimized for B1 + homogeneity and transmit efficiency. Peak SAR values due to the shifts of the array position increase up to ≈50%. The worst-case peak SAR value for a dental retainer was found to be in the range of 10% of the maximal SAR in the tissue within the array's borders. For the IUD and artificial hip joint implants the effect was found to be negligible (peak SAR < 1% of the SAR within array borders). In addition to simulations for cardiac MRI, we performed a preliminary B1 + shimming and SAR-safety analysis for the same RF-array at various positions lower on the body trunk to assess a potential application in imaging abdominopelvic organs (prostate, kidney, and liver). The most promising target for an ad hoc alternative application of the array was found to be the prostate.

Ultra-high field cardiac MRI in large animals and humans for translational cardiovascular research.

A key step in translational cardiovascular research is the use of large animal models to better understand normal and abnormal physiology, to test drugs or interventions, or to perform studies which would be considered unethical in human subjects. Ultrahigh field magnetic resonance imaging (UHF-MRI) at 7 T field strength is becoming increasingly available for imaging of the heart and, when compared to clinically established field strengths, promises better image quality and image information content, more precise functional analysis, potentially new image contrasts, and as all in-vivo imaging techniques, a reduction of the number of animals per study because of the possibility to scan every animal repeatedly. We present here a solution to the dual use problem of whole-body UHF-MRI systems, which are typically installed in clinical environments, to both UHF-MRI in large animals and humans. Moreover, we provide evidence that in such a research infrastructure UHF-MRI, and ideally combined with a standard small-bore UHF-MRI system, can contribute to a variety of spatial scales in translational cardiovascular research: from cardiac organoids, Zebra fish and rodent hearts to large animal models such as pigs and humans. We present pilot data from serial CINE, late gadolinium enhancement, and susceptibility weighted UHF-MRI in a myocardial infarction model over eight weeks. In 14 pigs which were delivered from a breeding facility in a national SARS-CoV-2 hotspot, we found no infection in the incoming pigs. Human scanning using CINE and phase contrast flow measurements provided good image quality of the left and right ventricle. Agreement of functional analysis between CINE and phase contrast MRI was excellent. MRI in arrested hearts or excised vascular tissue for MRI-based histologic imaging, structural imaging of myofiber and vascular smooth muscle cell architecture using high-resolution diffusion tensor imaging, and UHF-MRI for monitoring free radicals as a surrogate for MRI of reactive oxygen species in studies of oxidative stress are demonstrated. We conclude that UHF-MRI has the potential to become an important precision imaging modality in translational cardiovascular research.

MyoPS: A benchmark of myocardial pathology segmentation combining three-sequence cardiac magnetic resonance images.

Assessment of myocardial viability is essential in diagnosis and treatment management of patients suffering from myocardial infarction, and classification of pathology on the myocardium is the key to this assessment. This work defines a new task of medical image analysis, i.e., to perform myocardial pathology segmentation (MyoPS) combining three-sequence cardiac magnetic resonance (CMR) images, which was first proposed in the MyoPS challenge, in conjunction with MICCAI 2020. Note that MyoPS refers to both myocardial pathology segmentation and the challenge in this paper. The challenge provided 45 paired and pre-aligned CMR images, allowing algorithms to combine the complementary information from the three CMR sequences for pathology segmentation. In this article, we provide details of the challenge, survey the works from fifteen participants and interpret their methods according to five aspects, i.e., preprocessing, data augmentation, learning strategy, model architecture and post-processing. In addition, we analyze the results with respect to different factors, in order to examine the key obstacles and explore the potential of solutions, as well as to provide a benchmark for future research. The average Dice scores of submitted algorithms were 0.614±0.231 and 0.644±0.153 for myocardial scars and edema, respectively. We conclude that while promising results have been reported, the research is still in the early stage, and more in-depth exploration is needed before a successful application to the clinics. MyoPS data and evaluation tool continue to be publicly available upon registration via its homepage (www.sdspeople.fudan.edu.cn/zhuangxiahai/0/myops20/).

High-resolution imaging of the excised porcine heart at a whole-body 7 T MRI system using an 8Tx/16Rx pTx coil.

INTRODUCTION: MRI of excised hearts at ultra-high field strengths ([Formula: see text]≥7 T) can provide high-resolution, high-fidelity ground truth data for biomedical studies, imaging science, and artificial intelligence. In this study, we demonstrate the capabilities of a custom-built, multiple-element transceiver array customized for high-resolution imaging of excised hearts. METHOD: A dedicated 16-element transceiver loop array was implemented for operation in parallel transmit (pTx) mode (8Tx/16Rx) of a clinical whole-body 7 T MRI system. The initial adjustment of the array was performed using full-wave 3D-electromagnetic simulation with subsequent final fine-tuning on the bench. RESULTS: We report the results of testing the implemented array in tissue-mimicking liquid phantoms and excised porcine hearts. The array demonstrated high efficiency of parallel transmits characteristics enabling efficient pTX-based B1+-shimming. CONCLUSION: The receive sensitivity and parallel imaging capability of the dedicated coil were superior to that of a commercial 1Tx/32Rx head coil in both SNR and T2*-mapping. The array was successfully tested to acquire ultra-high-resolution (0.1 × 0.1 × 0.8 mm voxel) images of post-infarction scar tissue. High-resolution (isotropic 1.6 mm3 voxel) diffusion tensor imaging-based tractography provided high-resolution information about normal myocardial fiber orientation.

Effects of image homogeneity on stenosis visualization at 7 T in a coronary artery phantom study: With and without B1-shimming and parallel transmission.

BACKGROUND: To investigate the effects of B1-shimming and radiofrequency (RF) parallel transmission (pTX) on the visualization and quantification of the degree of stenosis in a coronary artery phantom using 7 Tesla (7 T) magnetic resonance imaging (MRI). METHODS: Stenosis phantoms with different grades of stenosis (0%, 20%, 40%, 60%, 80%, and 100%; 5 mm inner vessel diameter) were produced using 3D printing (clear resin). Phantoms were imaged with four different concentrations of diluted Gd-DOTA representing established arterial concentrations after intravenous injection in humans. Samples were centrally positioned in a thorax phantom of 30 cm diameter filled with a custom-made liquid featuring dielectric properties of muscle tissue. MRI was performed on a 7 T whole-body system. 2D-gradient-echo sequences were acquired with an 8-channel transmit 16-channel receive (8 Tx / 16 Rx) cardiac array prototype coil with and without pTX mode. Measurements were compared to those obtained with identical scan parameters using a commercially available 1 Tx / 16 Rx single transmit coil (sTX). To assess reproducibility, measurements (n = 15) were repeated at different horizontal angles with respect to the B0-field. RESULTS: B1-shimming and pTX markedly improved flip angle homogeneity across the thorax phantom yielding a distinctly increased signal-to-noise ratio (SNR) averaged over a whole slice relative to non-manipulated RF fields. Images without B1-shimming showed shading artifacts due to local B1+-field inhomogeneities, which hampered stenosis quantification in severe cases. In contrast, B1-shimming and pTX provided superior image homogeneity. Compared with a conventional sTX coil higher grade stenoses (60% and 80%) were graded significantly (p<0.01) more precise. Mild to moderate grade stenoses did not show significant differences. Overall, SNR was distinctly higher with B1-shimming and pTX than with the conventional sTX coil (inside the stenosis phantoms 14%, outside the phantoms 32%). Both full and half concentration (10.2 mM and 5.1 mM) of a conventional Gd-DOTA dose for humans were equally suitable for stenosis evaluation in this phantom study. CONCLUSIONS: B1-shimming and pTX at 7 T can distinctly improve image homogeneity and therefore provide considerably more accurate MR image analysis, which is beneficial for imaging of small vessel structures.

High-resolution simulation of B0 field conditions in the human heart from segmented computed tomography images.

B0 inhomogeneity leads to imaging artifacts in cardiac magnetic resonance imaging (MRI), in particular dark band artifacts with steady-state free precession pulse sequences. The limited spatial resolution of MR-derived in vivo B0 maps and the lack of population data prevent systematic analysis of the problem at hand and the development of optimized B0 shim strategies. We used readily available clinical computed tomography (CT) images to simulate the B0 conditions in the human heart at high spatial resolution. Calculated B0 fields showed consistency with MRI-based B0 measurements. The B0 maps for both the simulations and in vivo measurements showed local field inhomogeneities in the vicinity of lung tips with dominant Z3 spherical harmonic terms in the field distribution. The presented simulation approach allows for the derivation of B0 field conditions at high spatial resolution from CT images and enables the development of subject- and population-specific B0 shim strategies for the human heart.

Assessment of Myocardial Microstructure in a Murine Model of Obesity-Related Cardiac Dysfunction by Diffusion Tensor Magnetic Resonance Imaging at 7T.

Background: Obesity exerts multiple deleterious effects on the heart that may ultimately lead to cardiac failure. This study sought to characterize myocardial microstructure and function in an experimental model of obesity-related cardiac dysfunction. Methods: Male C57BL/6N mice were fed either a high-fat diet (HFD; 60 kcal% fat, n = 12) or standard control diet (9 kcal% fat, n = 10) for 15 weeks. At the end of the study period, cardiac function was assessed by ultra-high frequency echocardiography, and hearts were processed for further analyses. The three-dimensional myocardial microstructure was examined ex vivo at a spatial resolution of 100 × 100 × 100 µm3 by diffusion tensor magnetic resonance imaging (DT-MRI) at 7T. Myocardial deformation, diffusion metrics and fiber tract geometry were analyzed with respect to the different myocardial layers (subendocardium/subepicardium) and segments (base/mid-cavity/apex). Results were correlated with blood sample analyses, histopathology, and gene expression data. Results: HFD feeding induced significantly increased body weight combined with a pronounced accumulation of visceral fat (body weight 42.3 ± 5.7 vs. 31.5 ± 2.2 g, body weight change 73.7 ± 14.8 vs. 31.1 ± 6.6%, both P < 0.001). Obese mice showed signs of diastolic dysfunction, whereas left-ventricular ejection fraction and fractional shortening remained unchanged (E/e' 41.6 ± 16.6 vs. 24.8 ± 6.0, P < 0.01; isovolumic relaxation time 19 ± 4 vs. 14 ± 4 ms, P < 0.05). Additionally, global longitudinal strain was reduced in the HFD group (-15.1 ± 3.0 vs. -20.0 ± 4.6%, P = 0.01), which was mainly driven by an impairment in basal segments. However, histopathology and gene expression analyses revealed no myocardial fibrosis or differences in cardiomyocyte morphology. Mean diffusivity and eigenvalues of the diffusion tensor were lower in the basal subepicardium of obese mice as assessed by DT-MRI (P < 0.05). The three-dimensional fiber tract arrangement of the left ventricle (LV) remained preserved. Conclusion: Fifteen weeks of high-fat diet induced alterations in myocardial diffusion properties in mice, whereas no remodeling of the three-dimensional myofiber arrangement of the LV was observed. Obese mice showed reduced longitudinal strain and lower mean diffusivity predominantly in the left-ventricular base, and further investigation into the significance of this regional pattern is required.

A novel antisymmetric 16-element transceiver dipole antenna array for parallel transmit cardiac MRI in pigs at 7 T.

To improve parallel transmit (pTx) and receive performance for cardiac MRI (cMRI) in pigs at 7 T, a dedicated transmit/receive (Tx/Rx), 16-element antisymmetric dipole antenna array, which combines L-shaped and straight dipoles, was designed, implemented, and evaluated in both cadavers and animals in vivo. Electromagnetic-field simulations were performed with the new 16-element dipole antenna array loaded with a pig thorax-shaped phantom and compared with an eight-element array of straight dipoles. The new dipole array was interfaced to a 7 T scanner in pTx mode (8Tx/16Rx). Imaging performance of the novel array was validated through MRI measurements in a pig phantom, an 85 kg pig cadaver, and two pigs in vivo (74 and 81 kg). Due to the improved decoupling between interleaved L-shaped and straight dipole elements, the 16-element dipole array fits within the same outer dimensions as an eight-element array of straight dipoles. This provides improvement of both transmit and receive characteristics and additional degrees of freedom for B1+ shimming. The antisymmetric dipole array demonstrated efficient suppression of destructive interferences in the B1+ field, with up to 25% improvement in the B1+ homogeneity achieved using static pTx-RFPA B1+ shimming in comparison with the hardware-adjusted state, which was optimized for single transmit. High-resolution (0.5 × 0.5 × 4 mm3 ) anatomical images of the heart after cardiac arrest proved good transmit and receive characteristics of the novel array design. Parallel imaging with an acceleration factor up to R = 6 was possible while maintaining a mean g factor of 1.55 within the pig heart. CINE images acquired in vivo in two pigs demonstrated SNR and parallel imaging capabilities similar to those of a reference 8Tx/16Rx dedicated loop array for cMRI in pigs.

Validation of cardiac diffusion tensor imaging sequences: A multicentre test-retest phantom study.

Cardiac diffusion tensor imaging (DTI) is an emerging technique for the in vivo characterisation of myocardial microstructure, and there is a growing need for its validation and standardisation. We sought to establish the accuracy, precision, repeatability and reproducibility of state-of-the-art pulse sequences for cardiac DTI among 10 centres internationally. Phantoms comprising 0%-20% polyvinylpyrrolidone (PVP) were scanned with DTI using a product pulsed gradient spin echo (PGSE; N = 10 sites) sequence, and a custom motion-compensated spin echo (SE; N = 5) or stimulated echo acquisition mode (STEAM; N = 5) sequence suitable for cardiac DTI in vivo. A second identical scan was performed 1-9 days later, and the data were analysed centrally. The average mean diffusivities (MDs) in 0% PVP were (1.124, 1.130, 1.113) x 10-3  mm2 /s for PGSE, SE and STEAM, respectively, and accurate to within 1.5% of reference data from the literature. The coefficients of variation in MDs across sites were 2.6%, 3.1% and 2.1% for PGSE, SE and STEAM, respectively, and were similar to previous studies using only PGSE. Reproducibility in MD was excellent, with mean differences in PGSE, SE and STEAM of (0.3 ± 2.3, 0.24 ± 0.95, 0.52 ± 0.58) x 10-5  mm2 /s (mean ± 1.96 SD). We show that custom sequences for cardiac DTI provide accurate, precise, repeatable and reproducible measurements. Further work in anisotropic and/or deforming phantoms is warranted.

Global optimization of default phases for parallel transmit coils for ultra-high-field cardiac MRI.

The development of novel multiple-element transmit-receive arrays is an essential factor for improving B1+ field homogeneity in cardiac MRI at ultra-high magnetic field strength (B0 > = 7.0T). One of the key steps in the design and fine-tuning of such arrays during the development process is finding the default driving phases for individual coil elements providing the best possible homogeneity of the combined B1+-field that is achievable without (or before) subject-specific B1+-adjustment in the scanner. This task is often solved by time-consuming (brute-force) or by limited efficiency optimization methods. In this work, we propose a robust technique to find phase vectors providing optimization of the B1-homogeneity in the default setup of multiple-element transceiver arrays. The key point of the described method is the pre-selection of starting vectors for the iterative solver-based search to maximize the probability of finding a global extremum for a cost function optimizing the homogeneity of a shaped B1+-field. This strategy allows for (i) drastic reduction of the computation time in comparison to a brute-force method and (ii) finding phase vectors providing a combined B1+-field with homogeneity characteristics superior to the one provided by the random-multi-start optimization approach. The method was efficiently used for optimizing the default phase settings in the in-house-built 8Tx/16Rx arrays designed for cMRI in pigs at 7T.

Sensitivity analysis for interpretation of machine learning based segmentation models in cardiac MRI.

BACKGROUND: Image segmentation is a common task in medical imaging e.g., for volumetry analysis in cardiac MRI. Artificial neural networks are used to automate this task with performance similar to manual operators. However, this performance is only achieved in the narrow tasks networks are trained on. Performance drops dramatically when data characteristics differ from the training set properties. Moreover, neural networks are commonly considered black boxes, because it is hard to understand how they make decisions and why they fail. Therefore, it is also hard to predict whether they will generalize and work well with new data. Here we present a generic method for segmentation model interpretation. Sensitivity analysis is an approach where model input is modified in a controlled manner and the effect of these modifications on the model output is evaluated. This method yields insights into the sensitivity of the model to these alterations and therefore to the importance of certain features on segmentation performance. RESULTS: We present an open-source Python library (misas), that facilitates the use of sensitivity analysis with arbitrary data and models. We show that this method is a suitable approach to answer practical questions regarding use and functionality of segmentation models. We demonstrate this in two case studies on cardiac magnetic resonance imaging. The first case study explores the suitability of a published network for use on a public dataset the network has not been trained on. The second case study demonstrates how sensitivity analysis can be used to evaluate the robustness of a newly trained model. CONCLUSIONS: Sensitivity analysis is a useful tool for deep learning developers as well as users such as clinicians. It extends their toolbox, enabling and improving interpretability of segmentation models. Enhancing our understanding of neural networks through sensitivity analysis also assists in decision making. Although demonstrated only on cardiac magnetic resonance images this approach and software are much more broadly applicable.

Myocardial Infarction After High-Dose Catecholamine Application-A Case Report From an Experimental Imaging Study.

Although heart failure following myocardial infarction (MI) represents a major health burden, underlying microstructural and functional changes remain incompletely understood. Here, we report on a case of unexpected MI after treatment with the catecholamine isoproterenol in an experimental imaging study in mice using different state-of-the-art imaging modalities. The decline in cardiac function was documented by ultrahigh-frequency echocardiography and speckle-tracking analyses. Myocardial microstructure was studied ex vivo at a spatial resolution of 100 × 100 × 100 µm3 using diffusion tensor magnetic resonance imaging (DT-MRI) and histopathologic analyses. Two weeks after ISO treatment, the animal showed an apical aneurysm accompanied by reduced radial strain in corresponding segments and impaired global systolic function. DT-MRI revealed a loss of contractile fiber tracts together with a disarray of remaining fibers as corresponding microstructural correlates. This preclinical case report provides valuable insights into pathophysiology and morphologic-functional relations of heart failure following MI using emerging imaging technologies.

A Novel Mono-surface Antisymmetric 8Tx/16Rx Coil Array for Parallel Transmit Cardiac MRI in Pigs at 7T.

A novel mono-surface antisymmetric 16-element transmit/receive (Tx/Rx) coil array was designed, simulated, constructed, and tested for cardiac magnetic resonance imaging (cMRI) in pigs at 7 T. The cardiac array comprised of a mono-surface 16-loops with two central elements arranged anti-symmetrically and flanked by seven elements on either side. The array was configured for parallel transmit (pTx) mode to have an eight channel transmit and 16-channel receive (8Tx/16Rx) coil array. Electromagnetic (EM) simulations, bench-top measurements, phantom, and MRI experiments with two pig cadavers (68 and 46 kg) were performed. Finally, the coil was used in pilot in-vivo measurements with a 60 kg pig. Flip angle (FA), geometry factor (g-factor), signal-to-noise ratio (SNR) maps, and high-resolution cardiac images were acquired with an in-plane resolution of 0.6 mm × 0.6 mm (in-vivo) and 0.3 mm × 0.3 mm (ex-vivo). The mean g-factor over the heart was 1.26 (R = 6). Static phase [Formula: see text] shimming in a pig body phantom with the optimal phase vectors makes possible to improve the [Formula: see text] homogeneity by factor > 2 and transmit efficiency by factor > 3 compared to zero phases (before RF shimming). Parallel imaging performed in the in-vivo measurements demonstrated well preserved diagnostic quality of the resulting images at acceleration factors up to R = 6. The described hardware design can be adapted for arrays optimized for animals and humans with a larger number of elements (32-64) while maintaining good decoupling for various MRI applications at UHF (e.g., cardiac, head, and spine).

Influence of contrast agent dispersion on bolus-based MRI myocardial perfusion measurements: A computational fluid dynamics study.

PURPOSE: Bolus-based dynamic contrast agent (CA) perfusion measurements of the heart are subject to systematic errors due to CA bolus dispersion in the coronary arteries. To better understand these effects on quantification of myocardial blood flow and myocardial perfusion reserve (MPR), an in-silico model of the coronary arteries down to the pre-arteriolar vessels has been developed. METHODS: In this work, a computational fluid dynamics analysis is performed to investigate these errors on the basis of realistic 3D models of the left and right porcine coronary artery trees, including vessels at the pre-arteriolar level. Using advanced boundary conditions, simulations of blood flow and CA transport are conducted at rest and under stress. These are evaluated with regard to dispersion (assessed by the width of CA concentration time curves and associated vascular transport functions) and errors of myocardial blood flow and myocardial perfusion reserve quantification. RESULTS: Contrast agent dispersion increases with traveled distance as well as vessel diameter, and decreases with higher flow velocities. Overall, the average myocardial blood flow errors are -28% ± 16% and -8.5% ± 3.3% at rest and stress, respectively, and the average myocardial perfusion reserve error is 26% ± 22%. The calculated values are different in the left and right coronary tree. CONCLUSION: Contrast agent dispersion is dependent on a complex interplay of several different factors characterizing the cardiovascular bed, including vessel size and integrated vascular length. Quantification errors evoked by the observed CA dispersion show nonnegligible distortion in dynamic CA bolus-based perfusion measurements. We expect future improvements of quantitative perfusion measurements to make the systematic errors described here more apparent.

Characterization of Myocardial Microstructure and Function in an Experimental Model of Isolated Subendocardial Damage.

Subendocardial damage is among the first cardiac manifestations of hypertension and is already present in asymptomatic disease states. Accordingly, markers of subendocardial impairment may facilitate early detection of cardiac damages and risk stratification under these conditions. This study aimed to investigate the impact of subendocardial damage on myocardial microstructure and function to elucidate early pathophysiologic processes and to identify corresponding diagnostic measures. Mice (n=38) were injected with isoproterenol to induce isolated subendocardial scarring or saline as corresponding control. Cardiac function and myocardial deformation were determined by high-frequency echocardiography. The cardiac stress response was assessed in a graded exercise test and during dobutamine stress echocardiography. Myocardial microstructure was studied ex vivo by 7 T diffusion tensor magnetic resonance imaging at a spatial resolution of 100×100×100 µm 3 . Results were correlated with histology and biomarker expression. Subendocardial fibrosis was accompanied by diastolic dysfunction, impaired longitudinal deformation (global peak longitudinal strain [LS]: -12.5±0.5% versus -15.6±0.5%; P<0.001) and elevated biomarker expression (ANP [atrial natriuretic peptide], Galectin-3, and ST2). Systolic function and cardiac stress response remained preserved. Diffusion tensor magnetic resonance imaging revealed a left-shift in helix angle towards lower values in isoproterenol-treated animals, which was mainly determined by subepicardial myofibers (mean helix angle: 2.2±0.8° versus 5.9±1.0°; P<0.01). Longitudinal strain and subepicardial helix angle were highly predictive for subendocardial fibrosis (sensitivity, 82%-92% and specificity, 89%-90%). The results indicate that circumscribed subendocardial damage alone can cause several hallmarks observed in cardiovascular high-risk patients. Microstructural remodeling under these conditions involves also remote regions, and corresponding changes in longitudinal strain and helix angle might serve as diagnostic markers.

Magnetic resonance imaging of (1)H long lived states derived from parahydrogen induced polarization in a clinical system.

Hyperpolarization is a powerful tool to overcome the low sensitivity of nuclear magnetic resonance (NMR). However, applications are limited due to the short lifetime of this non equilibrium spin state caused by relaxation processes. This issue can be addressed by storing hyperpolarization in slowly decaying singlet spin states which was so far mostly demonstrated for non-proton spin pairs, e.g. (13)C-(13)C. Protons hyperpolarized by parahydrogen induced polarization (PHIP) in symmetrical molecules, are very well suited for this strategy because they naturally exhibit a long-lived singlet state. The conversion of the NMR silent singlet spin state to observable magnetization can be achieved by making use of singlet-triplet level anticrossings. In this study, a low-power radiofrequency pulse sequence is used for this purpose, which allows multiple successive singlet-triplet conversions. The generated magnetization is used to record proton images in a clinical magnetic resonance imaging (MRI) system, after 3min waiting time. Our results may open unprecedented opportunities to use the standard MRI nucleus (1)H for e.g. metabolic imaging in the future.

Resting myocardial blood flow quantification using contrast-enhanced magnetic resonance imaging in the presence of stenosis: A computational fluid dynamics study.

PURPOSE: The extent to which atherosclerotic plaques affect contrast agent (CA) transport in the coronary arteries and, hence, quantification of myocardial blood flow (MBF) using magnetic resonance imaging (MRI) is unclear. The purpose of this work was to evaluate the influence of plaque induced stenosis both on CA transport and on the accuracy of MBF quantification. METHODS: Computational fluid dynamics simulations in a high-detailed realistic vascular model were employed to investigate CA bolus transport in the coronary arteries. The impact of atherosclerosis was analyzed by inserting various medium- to high-grade stenoses in the vascular model. The influence of stenosis morphology was examined by varying the stenosis shapes but keeping the area reduction constant. Errors due to CA bolus transport were analyzed using the tracer-kinetic model MMID4. RESULTS: Dispersion of the CA bolus was found in all models and for all outlets, but with a varying magnitude. The impact of stenosis was complex: while high-grade stenoses amplified dispersion, mild stenoses reduced the effect. Morphology was found to have a marked influence on dispersion for a small number of outlets in the post-stenotic region. Despite this marked influence on the concentration-time curves, MBF errors were less affected by stenosis. In total, MBF was underestimated by -7.9% to -44.9%. CONCLUSIONS: The presented results reveal that local hemodynamics in the coronary vasculature appears to have a direct impact on CA bolus dispersion. Inclusion of atherosclerotic plaques resulted in a complex alteration of this effect, with both degree of area reduction and stenosis morphology affecting the amount of dispersion. This strong influence of vascular transport effects impairs the accuracy of MRI-based MBF quantification techniques and, potentially, other bolus-based perfusion measurement techniques like computed tomography perfusion imaging.