ECG-free cine MRI with data-driven clustering of cardiac motion for quantification of ventricular function.

BACKGROUND: Despite the widespread use of cine MRI for evaluation of cardiac function, existing real-time methods do not easily enable quantification of ventricular function. Moreover, segmented cine MRI assumes periodicity of cardiac motion. We aim to develop a self-gated, cine MRI acquisition scheme with data-driven cluster-based binning of cardiac motion. METHODS: A Cartesian golden-step balanced steady-state free precession sequence with sorted k-space ordering was designed. Image data were acquired with breath-holding. Principal component analysis and k-means clustering were used for binning of cardiac phases. Cluster compactness in the time dimension was assessed using temporal variability, and dispersion in the spatial dimension was assessed using the Calinski-Harabasz index. The proposed and the reference electrocardiogram (ECG)-gated cine methods were compared using a four-point image quality score, SNR and CNR values, and Bland-Altman analyses of ventricular function. RESULTS: A total of 10 subjects with sinus rhythm and 8 subjects with arrhythmias underwent cardiac MRI at 3.0 T. The temporal variability was 45.6 ms (cluster) versus 24.6 ms (ECG-based) (p < 0.001), and the Calinski-Harabasz index was 59.1 ± 9.1 (cluster) versus 22.0 ± 7.1 (ECG based) (p < 0.001). In subjects with sinus rhythm, 100% of the end-systolic and end-diastolic images from both the cluster and reference approach received the highest image quality score of 4. Relative to the reference cine images, the cluster-based multiphase (cine) image quality consistently received a one-point lower score (p < 0.05), whereas the SNR and CNR values were not significantly different (p = 0.20). In cases with arrhythmias, 97.9% of the end-systolic and end-diastolic images from the cluster approach received an image quality score of 3 or more. The mean bias values for biventricular ejection fraction and volumes derived from the cluster approach versus reference cine were negligible. CONCLUSION: ECG-free cine cardiac MRI with data-driven clustering for binning of cardiac motion is feasible and enables quantification of cardiac function.

Dynamic Regularized Adaptive Cluster Optimization (DRACO) for Quantitative Cardiac Cine MRI in Complex Arrhythmias.

BACKGROUND: Irregular cardiac motion can render conventional segmented cine MRI nondiagnostic. Clustering has been proposed for cardiac motion binning and may be optimized for complex arrhythmias. PURPOSE: To develop an adaptive cluster optimization method for irregular cardiac motion, and to generate the corresponding time-resolved cine images. STUDY TYPE: Prospective. SUBJECTS: Thirteen with atrial fibrillation, four with premature ventricular contractions, and one patient in sinus rhythm. FIELD STRENGTH/SEQUENCE: Free-running balanced steady state free precession (bSSFP) with sorted golden-step, reference real-time sequence. ASSESSMENT: Each subject underwent both the sorted golden-step bSSFP and the reference Cartesian real-time imaging. Golden-step bSSFP images were reconstructed using the dynamic regularized adaptive cluster optimization (DRACO) method and k-means clustering. Image quality (4-point Likert scale), signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), edge sharpness, and ventricular function were assessed. STATISTICAL TESTS: Paired t-tests, Friedman test, regression analysis, Fleiss' Kappa, Bland-Altman analysis. Significance level P < 0.05. RESULTS: The DRACO method had the highest percent of images with scores ≥3 (96% for diastolic frame, 93% for systolic frame, and 93% for multiphase cine) and the percentages were significantly higher compared with both the k-means and real-time methods. Image quality scores, SNR, and CNR were significantly different between DRACO vs. k-means and between DRACO vs. real-time. Cardiac function analysis showed no significant differences between DRACO vs. the reference real-time. CONCLUSION: DRACO with time-resolved reconstruction generated high quality images and has early promise for quantitative cine cardiac MRI in patients with complex arrhythmias including atrial fibrillation. TECHNICAL EFFICACY: Stage 2.

Ferumoxytol-Enhanced Cardiac Cine MRI Reconstruction Using a Variable-Splitting Spatiotemporal Network.

BACKGROUND: Balanced steady-state free precession (bSSFP) imaging is commonly used in cardiac cine MRI but prone to image artifacts. Ferumoxytol-enhanced (FE) gradient echo (GRE) has been proposed as an alternative. Utilizing the abundance of bSSFP images to develop a computationally efficient network that is applicable to FE GRE cine would benefit future network development. PURPOSE: To develop a variable-splitting spatiotemporal network (VSNet) for image reconstruction, trained on bSSFP cine images and applicable to FE GRE cine images. STUDY TYPE: Retrospective and prospective. SUBJECTS: 41 patients (26 female, 53 ± 19 y/o) for network training, 31 patients (19 female, 49 ± 17 y/o) and 5 healthy subjects (5 female, 30 ± 7 y/o) for testing. FIELD STRENGTH/SEQUENCE: 1.5T and 3T, bSSFP and GRE. ASSESSMENT: VSNet was compared to VSNet with total variation loss, compressed sensing and low rank methods for 14× accelerated data. The GRAPPA×2/×3 images served as the reference. Peak signal-to-noise-ratio (PSNR), structural similarity index (SSIM), left ventricular (LV) and right ventricular (RV) end-diastolic volume (EDV), end-systolic volume (ESV), and ejection fraction (EF) were measured. Qualitative image ranking and scoring were independently performed by three readers. Latent scores were calculated based on scores of each method relative to the reference. STATISTICS: Linear mixed-effects regression, Tukey method, Fleiss' Kappa, Bland-Altman analysis, and Bayesian categorical cumulative probit model. A P-value <0.05 was considered statistically significant. RESULTS: VSNet achieved significantly higher PSNR (32.7 ± 0.2), SSIM (0.880 ± 0.004), rank (2.14 ± 0.06), and latent scores (-1.72 ± 0.22) compared to other methods (rank >2.90, latent score < -2.63). Fleiss' Kappa was 0.52 for scoring and 0.61 for ranking. VSNet showed no significantly different LV and RV ESV (P = 0.938) and EF (P = 0.143) measurements, but statistically significant different (2.62 mL) EDV measurements compared to the reference. CONCLUSION: VSNet produced the highest image quality and the most accurate functional measurements for FE GRE cine images among the tested 14× accelerated reconstruction methods. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 1.

Fractional myocardial blood volume by ferumoxytol-enhanced MRI: Estimation of ischemic burden.

PURPOSE: To investigate model-fitted fractional myocardial blood volume (fMBV) derived from ferumoxytol-enhanced MRI as a measure of myocardial tissue hypoperfusion at rest. METHODS: We artificially induced moderate to severe focal coronary stenosis in the left anterior descending artery of 19 swine by percutaneous delivery of a 3D-printed coronary implant. Using the MOLLI pulse sequence, we acquired T1 maps at 3 T after multiple incremental ferumoxytol doses (0.0-4.0 mg/kg). We computed pixel-wise fMBV using a multi-compartmental modeling approach in 19 ischemic swine and 4 healthy swine. RESULTS: Ischemic myocardial segments showed a mean MRI-fMBV of 11.72 ± 3.00%, compared with 8.23 ± 2.12% in remote segments and 8.38 ± 2.23% in normal segments. Ischemic segments showed a restricted transvascular water-exchange rate (ki  = 15.32 ± 8.69 s-1 ) relative to remote segments (ki  = 17.78 [11.60, 26.36] s-1 ). A mixed-effects model found significant difference in fMBV (p = 0.002) and water-exchange rate (p < 0.001) between ischemic and remote myocardial regions after adjusting for biological sex and slice location. Analysis of fMBV as a predictor of impaired myocardial contractility using receiver operating characteristics showed an area under the curve of 0.89 (95% confidence interval [CI] 0.80, 0.95). An MRI-fMBV threshold of 9.60% has a specificity of 90.0% (95% CI 76.3, 97.2) and a sensitivity of 72.5% (95% CI 56.1, 83.4) for prediction of impaired myocardial contractility. CONCLUSIONS: Model-fitted fMBV derived from ferumoxytol-enhanced MRI can distinguish regions of ischemia from remote myocardium in a swine model of myocardial hypoperfusion.

Comparison of Three Ultrasmall, Superparamagnetic Iron Oxide Nanoparticles for MRI at 3.0 T.

BACKGROUND: The ultrasmall, superparamagnetic iron oxide (USPIO) nanoparticle ferumoxytol has unique applications in cardiac, vascular, and body magnetic resonance imaging (MRI) due to its long intravascular half-life and suitability as a blood pool agent. However, limited availability and high cost have hindered its clinical adoption. A new ferumoxytol generic, and the emergence of MoldayION as an alternative USPIO, represent opportunities to expand the use of USPIO-enhanced MRI techniques. PURPOSE: To compare in vitro and in vivo MRI relaxometry and enhancement of Feraheme, generic ferumoxytol, and MoldayION. STUDY TYPE: Prospective. ANIMAL MODEL: Ten healthy swine and six swine with artificially induced coronary narrowing underwent cardiac MRI. FIELD STRENGTH/SEQUENCE: 3.0 T; T1-weighted (4D-MUSIC, 3D-VIBE, 2D-MOLLI) and T2-weighted (2D-HASTE) sequences pre- and post-contrast. ASSESSMENT: We compared the MRI relaxometry of Feraheme, generic ferumoxytol, and MoldayION using saline, plasma, and whole blood MRI phantoms with contrast concentrations from 0.26 mM to 2.10 mM. In-vivo contrast effects on T1- and T2-weighted sequences and fractional intravascular contrast distribution volume in myocardium, liver, and spleen were evaluated. STATISTICAL TESTS: Analysis of variance and covariance were used for group comparisons. A P value <0.05 was considered statistically significant. RESULTS: The r1 relaxivities for Feraheme, generic ferumoxytol, and MoldayION in saline (22 °C) were 7.11 ± 0.13 mM-1  s-1 , 8.30 ± 0.29 mM-1  s-1 , 8.62 ± 0.16 mM-1  s-1 , and the r2 relaxivities were 111.74 ± 3.76 mM-1  s-1 , 105.07 ± 2.20 mM-1  s-1 , and 109.68 ± 2.56 mM-1  s-1 , respectively. The relationship between contrast concentration and longitudinal (R1) and transverse (R2) relaxation rate was highly linear in saline and plasma. The three agents produced similar in vivo contrast effects on T1 and T2 relaxation time-weighted sequences. DATA CONCLUSION: Relative to clinically approved ferumoxytol formulations, MoldayION demonstrates minor differences in in vitro relaxometry and comparable in vivo MRI characteristics. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

Plasma FGF23 is associated with left atrial remodeling in children on hemodialysis.

BACKGROUND: FGF23 mediates cardiac fibrosis through the activation of pro-fibrotic factors in in vitro models and is markedly elevated in kidney disease. Left atrial global longitudinal strain (LA GLS) derived by echocardiographic speckle-tracking measures longitudinal shortening of the LA walls, quantifies atrial performance and may enable detection of early LA remodeling in the setting of normal ventricular function. We hypothesized that LA GLS is abnormal in children on hemodialysis (HD) compared to healthy controls of comparable age/sex distribution and that, among HD patients, greater FGF23 levels are associated with abnormal LA GLS. METHODS: Clinical and echocardiographic data from 29 children receiving HD and 13 healthy controls were collected in a cross-sectional single-center study. Plasma FGF23 concentrations were measured using ELISA. The primary outcome was LA GLS measured using 2D speckle-tracking strain analysis. Linear regression analysis was used to investigate predictors of LA GLS in HD. RESULTS: Median dialysis vintage was 1.5 (IQR 0.5-4.3) years. Median intact FGF23 levels were substantially higher in the HD vs. control group (1206 [215, 4707] vs. 51 [43, 66.5] pg/ml; P = 0.0001), and LA GLS was 39.9% SD 11.6 vs. 32.8% SD 5.7 (P = 0.04). Among HD patients, higher FGF23 was associated with lower LA GLS (ß per unit Ln-FGF23: - 2.7; 95% CI slope - 5.4, - 0.1; P = 0.04 after adjustment for age, body size, and HD vintage. FGF23 was not associated with LA phasic reservoir, conduit, or contractile strain. CONCLUSIONS: In children on HD and preserved left ventricular ejection fraction, greater FGF23 is associated with lower LA GLS (indicative of impaired atrial performance). A higher resolution version of the Graphical abstract is available as Supplementary information.

Automatic segmentation of peripheral arteries and veins in ferumoxytol-enhanced MR angiography.

PURPOSE: To automate the segmentation of the peripheral arteries and veins in the lower extremities based on ferumoxytol-enhanced MR angiography (FE-MRA). METHODS: Our automated pipeline has 2 sequential stages. In the first stage, we used a 3D U-Net with local attention gates, which was trained based on a combination of the Focal Tversky loss with region mutual loss under a deep supervision mechanism to segment the vasculature from the high-resolution FE-MRA datasets. In the second stage, we used time-resolved images to separate the arteries from the veins. Because the ultimate segmentation quality of the arteries and veins relies on the performance of the first stage, we thoroughly evaluated the different aspects of the segmentation network and compared its performance in blood vessel segmentation with currently accepted state-of-the-art networks, including Volumetric-Net, DeepVesselNet-FCN, and Uception. RESULTS: We achieved a competitive F1 = 0.8087 and recall = 0.8410 for blood vessel segmentation compared with F1 = (0.7604, 0.7573, 0.7651) and recall = (0.7791, 0.7570, 0.7774) obtained with Volumetric-Net, DeepVesselNet-FCN, and Uception. For the artery and vein separation stage, we achieved F1 = (0.8274/0.7863) in the calf region, which is the most challenging region in peripheral arteries and veins segmentation. CONCLUSION: Our pipeline is capable of fully automatic vessel segmentation based on FE-MRA without need for human interaction in <4 min. This method improves upon manual segmentation by radiologists, which routinely takes several hours.

Free-breathing, non-ECG, simultaneous myocardial T1 , T2 , T2 *, and fat-fraction mapping with motion-resolved cardiovascular MR multitasking.

PURPOSE: To develop a free-breathing, non-electrocardiogram technique for simultaneous myocardial T1 , T2 , T2 *, and fat-fraction (FF) mapping in a single scan. METHODS: The MR Multitasking framework is adapted to quantify T1 , T2 , T2 *, and FF simultaneously. A variable TR scheme is developed to preserve temporal resolution and imaging efficiency. The underlying high-dimensional image is modeled as a low-rank tensor, which allows accelerated acquisition and efficient reconstruction. The accuracy and/or repeatability of the technique were evaluated on static and motion phantoms, 12 healthy volunteers, and 3 patients by comparing to the reference techniques. RESULTS: In static and motion phantoms, T1 /T2 /T2 */FF measurements showed substantial consistency (R > 0.98) and excellent agreement (intraclass correlation coefficient > 0.93) with reference measurements. In human subjects, the proposed technique yielded repeatable T1 , T2 , T2 *, and FF measurements that agreed with those from references. CONCLUSIONS: The proposed free-breathing, non-electrocardiogram, motion-resolved Multitasking technique allows simultaneous quantification of myocardial T1 , T2 , T2 *, and FF in a single 2.5-min scan.

Four-dimensional Multiphase Steady-State MRI with Ferumoxytol Enhancement: Early Multicenter Feasibility in Pediatric Congenital Heart Disease.

Background The value of MRI in pediatric congenital heart disease (CHD) is well recognized; however, the requirement for expert oversight impedes its widespread use. Four-dimensional (4D) multiphase steady-state imaging with contrast enhancement (MUSIC) is a cardiovascular MRI technique that uses ferumoxytol and captures all anatomic features dynamically. Purpose To evaluate multicenter feasibility of 4D MUSIC MRI in pediatric CHD. Materials and Methods In this prospective study, participants with CHD underwent 4D MUSIC MRI at 3.0 T or 1.5 T between 2014 and 2020. From a pool of 460 total studies, an equal number of MRI studies from three sites (n = 60) was chosen for detailed analysis. With use of a five-point scale, the feasibility of 4D MUSIC was scored on the basis of artifacts, image quality, and diagnostic confidence for intracardiac and vascular connections (n = 780). Respiratory motion suppression was assessed by using the signal intensity profile. Bias between 4D MUSIC and two-dimensional (2D) cine imaging was evaluated by using Bland-Altman analysis; 4D MUSIC examination duration was compared with that of the local standard for CHD. Results A total of 206 participants with CHD underwent MRI at 3.0 T, and 254 participants underwent MRI at 1.5 T. Of the 60 MRI examinations chosen for analysis (20 per site; median participant age, 14.4 months [interquartile range, 2.3-49 months]; 33 female participants), 56 (93%) had good or excellent image quality scores across a spectrum of disease complexity (mean score ± standard deviation: 4.3 ± 0.6 for site 1, 4.9 ± 0.3 for site 2, and 4.6 ± 0.7 for site 3; P < .001). Artifact scores were inversely related to image quality (r = -0.88, P < .001) and respiratory motion suppression (P < .001, r = -0.45). Diagnostic confidence was high or definite in 730 of 780 (94%) intracardiac and vascular connections. The correlation between 4D MUSIC and 2D cine ventricular volumes and ejection fraction was high (range of r = 0.72-0.85; P < .001 for all). Compared with local standard MRI, 4D MUSIC reduced the image acquisition time (44 minutes ± 20 vs 12 minutes ± 3, respectively; P < .001). Conclusion Four-dimensional multiphase steady-state imaging with contrast enhancement MRI in pediatric congenital heart disease was feasible in a multicenter setting, shortened the examination time, and simplified the acquisition protocol, independently of disease complexity. Clinical trial registration no. NCT02752191 © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Roest and Lamb in this issue.

Slice encoding for the reduction of outflow signal artifacts in cine balanced SSFP imaging.

PURPOSE: Standard balanced SSFP (bSSFP) cine MRI often suffers from blood outflow artifacts. We propose a method that spatially encodes these outflowing spins to reduce their effects in the intended slice. METHODS: Bloch simulations were performed to characterize through-plane flow and to investigate how the use of phase encoding along the slice select's direction ("slice encoding") could alleviate its issues. Phantom scans and in vivo cines were acquired on a 3T system, comparing the standard 2D acquisition to the proposed slice-encoding method. Nineteen healthy volunteers were recruited for short-axis and horizontal long-axis oriented scans. An expert radiologist evaluated each slice-encoded/standard cine pairs in a rank comparison test and graded their quality on a 1-5 scale. The grades were used for a nonparametric paired evaluation for independent samples with a null hypothesis that there was no statistical difference between the two quality-grade distributions for α = 0.05 significance. RESULTS: Bloch simulation results demonstrated this technique's feasibility, showing a fully resolved slice profile given a sufficient number of slice encodes. These results were confirmed with the phantom experiments. Each in vivo slice-encoded cine had a higher quality than its corresponding standard acquisition. The nonparametric paired evaluation came to 0.01 significance, encouraging us to reject the null hypothesis and conclude that slice-encoding effectively works in reducing outflow effects. CONCLUSION: The slice-encoding balanced SSFP technique is helpful in mitigating outflow effects and is achievable within a single breath hold, being a useful alternative for cases in which the flow artifacts are significant.

Temporally aware volumetric generative adversarial network-based MR image reconstruction with simultaneous respiratory motion compensation: Initial feasibility in 3D dynamic cine cardiac MRI.

PURPOSE: Develop a novel three-dimensional (3D) generative adversarial network (GAN)-based technique for simultaneous image reconstruction and respiratory motion compensation of 4D MRI. Our goal was to enable high-acceleration factors 10.7X-15.8X, while maintaining robust and diagnostic image quality superior to state-of-the-art self-gating (SG) compressed sensing wavelet (CS-WV) reconstruction at lower acceleration factors 3.5X-7.9X. METHODS: Our GAN was trained based on pixel-wise content loss functions, adversarial loss function, and a novel data-driven temporal aware loss function to maintain anatomical accuracy and temporal coherence. Besides image reconstruction, our network also performs respiratory motion compensation for free-breathing scans. A novel progressive growing-based strategy was adapted to make the training process possible for the proposed GAN-based structure. The proposed method was developed and thoroughly evaluated qualitatively and quantitatively based on 3D cardiac cine data from 42 patients. RESULTS: Our proposed method achieved significantly better scores in general image quality and image artifacts at 10.7X-15.8X acceleration than the SG CS-WV approach at 3.5X-7.9X acceleration (4.53 ± 0.540 vs. 3.13 ± 0.681 for general image quality, 4.12 ± 0.429 vs. 2.97 ± 0.434 for image artifacts, P < .05 for both). No spurious anatomical structures were observed in our images. The proposed method enabled similar cardiac-function quantification as conventional SG CS-WV. The proposed method achieved faster central processing unit-based image reconstruction (6 s/cardiac phase) than the SG CS-WV (312 s/cardiac phase). CONCLUSION: The proposed method showed promising potential for high-resolution (1 mm3 ) free-breathing 4D MR data acquisition with simultaneous respiratory motion compensation and fast reconstruction time.

Retrospective respiratory motion correction in cardiac cine MRI reconstruction using adversarial autoencoder and unsupervised learning.

The aim of this study was to develop a deep neural network for respiratory motion compensation in free-breathing cine MRI and evaluate its performance. An adversarial autoencoder network was trained using unpaired training data from healthy volunteers and patients who underwent clinically indicated cardiac MRI examinations. A U-net structure was used for the encoder and decoder parts of the network and the code space was regularized by an adversarial objective. The autoencoder learns the identity map for the free-breathing motion-corrupted images and preserves the structural content of the images, while the discriminator, which interacts with the output of the encoder, forces the encoder to remove motion artifacts. The network was first evaluated based on data that were artificially corrupted with simulated rigid motion with regard to motion-correction accuracy and the presence of any artificially created structures. Subsequently, to demonstrate the feasibility of the proposed approach in vivo, our network was trained on respiratory motion-corrupted images in an unpaired manner and was tested on volunteer and patient data. In the simulation study, mean structural similarity index scores for the synthesized motion-corrupted images and motion-corrected images were 0.76 and 0.93 (out of 1), respectively. The proposed method increased the Tenengrad focus measure of the motion-corrupted images by 12% in the simulation study and by 7% in the in vivo study. The average overall subjective image quality scores for the motion-corrupted images, motion-corrected images and breath-held images were 2.5, 3.5 and 4.1 (out of 5.0), respectively. Nonparametric-paired comparisons showed that there was significant difference between the image quality scores of the motion-corrupted and breath-held images (P < .05); however, after correction there was no significant difference between the image quality scores of the motion-corrected and breath-held images. This feasibility study demonstrates the potential of an adversarial autoencoder network for correcting respiratory motion-related image artifacts without requiring paired data.

Ferumoxytol-enhanced magnetic resonance T1 reactivity for depiction of myocardial hypoperfusion.

Myocardial T1 reactivity, defined as the relative change in T1 between rest and vasodilator-induced stress, has been proposed as a magnetic resonance imaging (MRI) biomarker of tissue perfusion. We hypothesize that the superparamagnetic iron-oxide nanoparticle, ferumoxytol, sensitizes T1 to changes in the intramyocardial vascular compartment and improves the sensitivity and specificity of T1 reactivity as an imaging biomarker of tissue perfusion. We aim to assess the diagnostic performance of ferumoxytol-enhanced (FE) myocardial T1 reactivity in swine models of myocardial hypoperfusion. We induced acute myocardial hypoperfusion in 13 swine via percutaneous, transcatheter deployment of a 3D printed intracoronary stenosis implant into the left anterior descending coronary artery. We performed native and FE adenosine stress testing using 5(3)3(3)3 MOLLI and SASHA T1 mapping sequences with bSSFP readout on a clinical 3.0 T magnet. MOLLI T1 maps were fitted using both the conventional MOLLI and the Instantaneous Signal Loss (InSiL) T1-fitting algorithms. Regardless of the MOLLI or SASHA pulse sequence or T1-fitting algorithm, ferumoxytol contrast increased the dynamic range of T1 reactivity in both the remote and ischemic myocardial regions. Relative to remote myocardium, native and FE T1 reactivity were blunted in ischemic myocardium (p < 0.05) with InSiL-MOLLI, MOLLI and SASHA. An InSiL-MOLLI-derived FE T1 reactivity threshold of -4.65% had 73.3% sensitivity and 96.2% specificity for prediction of regional wall motion abnormalities (AUC 0.915, 95% CI 0.786-0.979), whereas a SASHA-derived FE T1 reactivity threshold of -5.25% had 75.0% sensitivity and 95.2% specificity (AUC 0.905, 95% CI 0.751-0.979). Ferumoxytol significantly increased the dynamic range of T1 reactivity as a measure of myocardial hypoperfusion in vasodilator stress T1 mapping studies. FE T1 reactivity maps can be used to quantitatively distinguish ischemic and remote myocardium with high specificity in swine models of acute myocardial hypoperfusion.

Estimation of fractional myocardial blood volume and water exchange using ferumoxytol-enhanced magnetic resonance imaging.

Fractional myocardial blood volume (fMBV) estimated using ferumoxytol-enhanced magnetic resonance imaging (MRI) (FE-MRI) has the potential to capture a hemodynamic response to myocardial hypoperfusion during contrast steady state without reliance on gadolinium chelates. Ferumoxytol has a long intravascular half-life and its use for steady-state MRI is off-label. The aim of this prospective study was to optimize and evaluate a two-compartment model for estimation of fMBV based on FE-MRI. Nine healthy swine and one swine with artificially induced single-vessel coronary stenosis underwent MRI on a 3.0 T clinical magnet. Myocardial longitudinal spin-lattice relaxation rate (R1) was measured using the 5(3)3(3)3 modified Look-Locker inversion recovery (MOLLI) sequence before and at contrast steady state following seven ferumoxytol infusions (0.125-4.0 mg/kg). fMBV and water exchange were estimated using a two-compartment model. Model-fitted fMBV was compared to simple fast-exchange fMBV approximation and percent change in pre- and postferumoxytol R1. Dose undersampling schemes were investigated to reduce acquisition duration. Variation in fMBV was assessed using one-way analysis of variance. Fast-exchange fMBV and ferumoxytol dose undersampling were evaluated using Bland-Altman analysis. Healthy normal swine showed a mean mid-ventricular fMBV of 7.2 ± 1.4% and water exchange rate of 11.3 ± 5.1 s-1 . There was intersubject variation in fMBV (p < 0.05) without segmental variation (p = 0.387). fMBV derived from eight-dose and four-dose sampling schemes had no significant bias (mean difference = 0.07, p = 0.541, limits of agreement -1.04% [-1.45, -0.62%] to 1.18% [0.77, 1.59%]). Pixel-wise fMBV in one swine model with coronary artery stenosis showed elevated fMBV in ischemic segments (apical anterior: 11.90 ± 4.00%, apical septum: 16.10 ± 5.71%) relative to remote segments (apical inferior: 9.59 ± 3.35%, apical lateral: 9.38 ± 2.35%). A two-compartment model based on FE-MRI using the MOLLI sequence may enable estimation of fMBV in studies of ischemic heart disease. LEVEL OF EVIDENCE: 2. TECHNICAL EFFICACY STAGE: 2.

18F-Sodium fluoride uptake is associated with severity of atherosclerotic stenosis in stable ischemic heart disease.

BACKGROUND: Increased uptake of 18F-Sodium fluoride (18F-NaF) PET has potential to identify atherosclerotic plaques that are vulnerable to rupture. Whether 18F-NaF PET can evaluate the significance of atherosclerotic plaque in patients with stable coronary artery disease is less clear. We evaluated 18F-NaF PET uptake in coronary arteries in patients without acute coronary artery syndrome to determine the association of 18F-NaF signal uptake with severity of coronary stenosis. METHODS AND RESULTS: We retrospectively identified 114 patients who received both regadenoson stress 82Rb myocardial perfusion PET and 18F-NaF PET study with an average interval of 5 months. Out of this cohort, forty-one patients underwent invasive coronary angiography. In a patient-based analysis, patients with ischemic regadenoson stress 82Rb PET had significantly higher coronary 18F-NaF uptake than patients with normal myocardial perfusion (P < .01). Among the 41 patients who underwent coronary angiography, per-vessel 18F-NaF uptake in both obstructive and nonobstructive coronary arteries was significantly higher than in normal coronary arteries (P < .05) regardless of the severity of coronary calcification. There was poor correlation between calcification and 18F-NaF uptake in coronary arteries (r = 0.41) CONCLUSION: Coronary arterial 18F-NaF uptake is associated with coronary stenosis severity in patients with stable coronary artery disease. 18F-NaF PET studies may be useful for characterizing coronary atherosclerotic plaques.

Cardiac Magnetic Resonance Quantification of Structure-Function Relationships in Heart Failure.

Classification of heart failure is based on the left ventricular ejection fraction (EF): preserved EF, midrange EF, and reduced EF. There remains an unmet need for further heart failure phenotyping of ventricular structure-function relationships. Because of high spatiotemporal resolution, cardiac magnetic resonance (CMR) remains the reference modality for quantification of ventricular contractile function. The authors aim to highlight novel frameworks, including theranostic use of ferumoxytol, to enable more efficient evaluation of ventricular function in heart failure patients who are also frequently anemic, and to discuss emerging quantitative CMR approaches for evaluation of ventricular structure-function relationships in heart failure.

Myocardial Steatosis Among Antiretroviral Therapy-Treated People With Human Immunodeficiency Virus Participating in the REPRIEVE Trial.

BACKGROUND: People with human immunodeficiency virus (PWH) face increased risks for heart failure and adverse heart failure outcomes. Myocardial steatosis predisposes to diastolic dysfunction, a heart failure precursor. We aimed to characterize myocardial steatosis and associated potential risk factors among a subset of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) participants. METHODS: Eighty-two PWH without known heart failure successfully underwent cardiovascular magnetic resonance spectroscopy, yielding data on intramyocardial triglyceride (IMTG) content (a continuous marker for myocardial steatosis extent). Logistic regression models were applied to investigate associations between select clinical characteristics and odds of increased or markedly increased IMTG content. RESULTS: Median (Q1, Q3) IMTG content was 0.59% (0.28%, 1.15%). IMTG content was increased (> 0.5%) among 52% and markedly increased (> 1.5%) among 22% of participants. Parameters associated with increased IMTG content included age (P = .013), body mass index (BMI) ≥ 25 kg/m2 (P = .055), history of intravenous drug use (IVDU) (P = .033), and nadir CD4 count < 350 cells/mm³ (P = .055). Age and BMI ≥ 25 kg/m2 were additionally associated with increased odds of markedly increased IMTG content (P = .049 and P = .046, respectively). CONCLUSIONS: A substantial proportion of antiretroviral therapy-treated PWH exhibited myocardial steatosis. Age, BMI ≥ 25 kg/m2, low nadir CD4 count, and history of IVDU emerged as possible risk factors for myocardial steatosis in this group. CLINICAL TRIALS REGISTRATION: NCT02344290; NCT03238755.

Pathophysiology, classification, and MRI parallels in microvascular disease of the heart and brain.

Diagnostic imaging technology in vascular disease has long focused on large vessels and the pathologic processes that impact them. With improved diagnostic techniques, investigators are now able to uncover many underlying mechanisms and prognostic factors for microvascular disease. In the heart and brain, these pathologic entities include coronary microvascular disease and cerebral small vessel disease, both of which have significant impact on patients, causing angina, myocardial infarction, heart failure, stroke, and dementia. In the current paper, we will discuss parallels in pathophysiology, classification, and diagnostic modalities, with a focus on the role of magnetic resonance imaging in microvascular disease of the heart and brain. Novel approaches for streamlined imaging of the cardiac and central nervous systems including the use of intravascular contrast agents such as ferumoxytol are presented, and unmet research gaps in diagnostics are summarized.

Fast and accurate calculation of myocardial T1 and T2 values using deep learning Bloch equation simulations (DeepBLESS).

PURPOSE: To propose and evaluate a deep learning model for rapid and accurate calculation of myocardial T1 /T2 values based on a previously proposed Bloch equation simulation with slice profile correction (BLESSPC) method. METHODS: Deep learning Bloch equation simulations (DeepBLESS) models are proposed for rapid and accurate T1 estimation for the MOLLI T1 mapping sequence with balanced SSFP readouts and T1 /T2 estimation for a radial simultaneous T1 and T2 mapping (radial T1 -T2 ) sequence. The DeepBLESS models were trained separately based on simulated radial T1 -T2 and MOLLI data, respectively. The DeepBLESS T1 -T2 estimation accuracy was evaluated based on simulated data with different noise levels. The DeepBLESS model was compared with BLESSPC in simulation, phantom, and in vivo studies for the MOLLI sequence at 1.5 T and radial T1 -T2 sequence at 3 T. RESULTS: After DeepBLESS was trained, in phantom studies, DeepBLESS and BLESSPC achieved similar accuracy and precision in T1 -T2 estimations for both MOLLI and radial T1 -T2 (P > .05). For in vivo, DeepBLESS and BLESSPC generated similar myocardial T1 /T2 values for radial T1 -T2 at 3 T (T1 : 1366 ± 31 ms for both methods, P > .05; T2 : 37.4 ms ± 0.9 ms for both methods, P > .05), and similar myocardial T1 values for the MOLLI sequence at 1.5 T (1044 ± 20 ms for both methods, P > .05). DeepBLESS generated a T1 /T2 map in less than 1 second. CONCLUSION: The DeepBLESS model offers an almost instantaneous approach for estimating accurate T1 /T2 values, replacing BLESSPC for both MOLLI and radial T1 -T2 sequences, and is promising for multiparametric mapping in cardiac MRI.

Intermodality feature fusion combining unenhanced computed tomography and ferumoxytol-enhanced magnetic resonance angiography for patient-specific vascular mapping in renal impairment.

OBJECTIVE: The purpose of this study was to establish the feasibility of fusing complementary, high-contrast features from unenhanced computed tomography (CT) and ferumoxytol-enhanced magnetic resonance angiography (FE-MRA) for preprocedural vascular mapping in patients with renal impairment. METHODS: In this Institutional Review Board-approved and Health Insurance Portability and Accountability Act-compliant study, 15 consecutive patients underwent both FE-MRA and unenhanced CT scanning, and the complementary high-contrast features from both modalities were fused to form an integrated, multifeature image. Source images from CT and MRA were segmented and registered. To validate the accuracy, precision, and concordance of fused images to source images, unambiguous landmarks, such as wires from implantable medical devices or indwelling catheters, were marked on three-dimensional (3D) models of the respective modalities, followed by rigid co-registration, interactive fusion, and fine adjustment. We then compared the positional offsets using pacing wires or catheters in the source FE-MRA (defined as points of interest [POIs]) and fused images (n = 5 patients, n = 247 points). Points within 3D image space were referenced to the respective modalities: x (right-left), y (anterior-posterior), and z (cranial-caudal). The respective 3D orthogonal reference axes from both image sets were aligned, such that with perfect registration, a given point would have the same (x, y, z) component values in both sets. The 3D offsets (Δx mm, Δy mm, Δz mm) for each of the corresponding POIs represent nonconcordance between the source FE-MRA and fused images. The offsets were compared using concordance correlation coefficients. Interobserver agreement was assessed using intraclass correlation coefficients and Bland-Altman analyses. RESULTS: Thirteen patients (aged 76 ± 12 years; seven female) with aortic valve stenosis and chronic kidney disease and two patients with thoracoabdominal vascular aneurysms and chronic kidney disease underwent FE-MRA for preprocedural vascular assessment, and unenhanced CT examinations were available in all patients. No ferumoxytol-related adverse events occurred. There were 247 matched POIs evaluated on the source FE-MRA and fused images. In patients with implantable medical devices, the mean offsets in spatial position were 0.31 ± 0.51 mm (ρ = 0.99; Cb = 1; 95% confidence interval [CI], 0.99-0.99) for Δx, 0.27 ± 0.69 mm (ρ = 0.99; Cb = 0.99; 95% CI, 0.99-0.99) for Δy, and 0.20 ± 0.59 mm (ρ = 1; Cb = 1; 95% CI, 0.99-1.00) for Δz. Interobserver agreement was excellent (intraclass correlation coefficient, >0.99). The mean difference in offset between readers was 1.5 mm. CONCLUSIONS: Accurate 3D feature fusion is feasible, combining luminal information from FE-MRA with vessel wall information on unenhanced CT. This framework holds promise for combining the complementary strengths of magnetic resonance imaging and CT to generate information-rich, multifeature composite vascular images while avoiding the respective risks and limitations of both modalities.