Cine MRI-Derived Radiomics Features of the Cardiac Blood Pool: Periodicity, Specificity, and Reproducibility.

BACKGROUND: Although radiomics features of the left ventricular wall have been used to assess cardiac diseases, radiomics features of the cardiac blood pool have been relatively ignored. PURPOSE: To test the hypothesis that cine MRI-derived radiomics features of the cardiac blood pool are associated with cardiac function and motion. STUDY TYPE: Retrospective. POPULATION: A total of 26 healthy volunteers (51.2 ± 15.6 years; 17 males). FIELD STRENGTH/SEQUENCE: A 1.5 T/balanced steady-state free precession (bSSFP). ASSESSMENT: The radiomics features (107 features in seven classes) of the blood pool of the left/right ventricle/atrium (LV/RV/LA/RA) were extracted on four-chamber cine images (25 phases). Conventional cardiac function parameters (volumes, ejection fraction [EF] and longitudinal strain) were assessed in each cardiac chamber. Intraobserver- and interobserver agreements of radiomics features of all chambers acquired at all phases were assessed, as well as scan-rescan agreement in a subset of 13 volunteers. STATISTICAL TESTS: Pearson correlation coefficients (r) were used to assess the associations between peak values of radiomics features and end-diastolic (or maximal) volume, end-systolic (or minimal) volume, EF, and longitudinal strain of corresponding chambers. Good intraobserver, interobserver, and scan-rescan agreements for radiomics features acquired were defined as intraclass correlation coefficient (ICC) > 0.7 or coefficient of variation (CoV) < 20%. RESULTS: Most radiomics features of the blood pool varied periodically throughout the cardiac cycle. Peak values of chamber-specific blood pool radiomics features were correlated with traditional cardiac function and motion indices of corresponding chambers (r: 0.4-0.87). Ninety-three (87%), 86 (80%), and 73 (68%) radiomics features demonstrated good intraobserver, interobserver, and scan-rescan reproducibility, respectively. CONCLUSION: Cine MRI-derived radiomics features within LV/RV/LA/RA are associated with traditional cardiac function and motion indices of corresponding chambers and may have the potential to become novel quantitative imaging biomarkers in cardiovascular medicine. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: 1.

Quantitative Assessment of Regional Pulmonary Transit Times in Pulmonary Hypertension.

BACKGROUND: Pulmonary hypertension (PH) contributes to restricted flow through the pulmonary circulation characterized by elevated mean pulmonary artery pressure acquired from invasive right heart catheterization (RHC). MRI may provide a noninvasive alternative for diagnosis and characterization of PH. PURPOSE: To characterize PH via quantification of regional pulmonary transit times (rPTT). STUDY TYPE: Retrospective. POPULATION: A total of 43 patients (58% female); 24 controls (33% female). RHC-confirmed patients classified as World Health Organization (WHO) subgroups 1-4. FIELD STRENGTH/SEQUENCE: A 1.5 T/time-resolved contrast-enhanced MR Angiography (CE-MRA). ASSESSMENT: CE-MRA data volumes were combined into a 4D matrix (3D resolution + time). Contrast agent arrival time was defined as the peak in the signal-intensity curve generated for each voxel. Average arrival times within a vessel region of interest (ROI) were normalized to the main pulmonary artery ROI (t0 ) for eight regions to define rPTT for all subjects. Subgroup analysis included grouping the four arterial and four venous regions. Intraclass correlation analysis completed for reproducibility. STATISTICAL TESTS: Analysis of covariance with age as covariate. A priori Student's t-tests or Wilcoxon rank-sum test; α = 0.05. Results compared to controls unless noted. Significant without listing P value. ICC ran as two-way absolute agreement model with two observers. RESULTS: PH patients demonstrated elevated rPTT in all vascular regions; average rPTT increase in arterial and venous branches was 0.85 ± 0.15 seconds (47.7%) and 1.0 ± 0.18 seconds (16.9%), respectively. Arterial rPTT was increased for all WHO subgroups; venous regions were elevated for subgroups 2 and 4 (group 1, P = 0.86; group 3, P = 0.32). No significant rPTT differences were found between subgroups (P = 0.094-0.94). Individual vessel ICC values ranged from 0.58 to 0.97. DATA CONCLUSION: Noninvasive assessment of PH using standard-of-care time-resolved CE-MRA can detect increased rPTT in PH patients of varying phenotypes compared to controls. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 3.

Systolic reverse flow derived from 4D flow cardiovascular magnetic resonance in bicuspid aortic valve is associated with aortic dilation and aortic valve stenosis: a cross sectional study in 655 subjects.

BACKGROUND: Bicuspid aortic valve (BAV) disease is associated with increased risk of aortopathy. In addition to current intervention guidelines, BAV mediated changes in aortic 3D hemodynamics have been considered as risk stratification measures. We aimed to evaluate the association of 4D flow cardiovascular magnetic resonance (CMR) derived voxel-wise aortic reverse flow with aortic dilation and to investigate the role of aortic valve regurgitation (AR) and stenosis (AS) on reverse flow in systole and diastole. METHODS: 510 patients with BAV (52 ± 14 years) and 120 patients with trileaflet aortic valve (TAV) (61 ± 11 years) and mid-ascending aorta diameter (MAAD) > 35 mm who underwent CMR including 4D flow CMR were retrospectively included. An age and sex-matched healthy control cohort (n = 25, 49 ± 12 years) was selected. Voxel-wise reverse flow was calculated in the aorta and quantified by the mean reverse flow in the ascending aorta (AAo) during systole and diastole. RESULTS: BAV patients without AS and AR demonstrated significantly increased systolic and diastolic reverse flow (222% and 13% increases respectively, p < 0.01) compared to healthy controls and also had significantly increased systolic reverse flow compared to TAV patients with aortic dilation (79% increase, p < 0.01). In patients with isolated AR, systolic and diastolic AAo reverse flow increased significantly with AR severity (c = - 83.2 and c = - 205.6, p < 0.001). In patients with isolated AS, AS severity was associated with an increase in both systolic (c = - 253.1, p < 0.001) and diastolic (c = - 87.0, p = 0.02) AAo reverse flow. Right and left/right and non-coronary fusion phenotype showed elevated systolic reverse flow (> 17% increase, p < 0.01). Right and non-coronary fusion phenotype showed decreased diastolic reverse flow (> 27% decrease, p < 0.01). MAAD was an independent predictor of systolic (p < 0.001), but not diastolic, reverse flow (p > 0.1). CONCLUSION: 4D flow CMR derived reverse flow associated with BAV was successfully captured even in the absence of AR or AS and in comparison to TAV patients with aortic dilation. Diastolic AAo reverse flow increased with AR severity while AS severity strongly correlated with increased systolic reverse flow in the AAo. Additionally, increasing MAAD was independently associated with increasing systolic AAo reverse flow. Thus, systolic AAo reverse flow may be a valuable metric for evaluating disease severity in future longitudinal outcome studies.

Alirocumab and plaque volume, calf muscle blood flow, and walking performance in peripheral artery disease: A randomized clinical trial.

BACKGROUND: The distal superficial femoral artery (SFA) is most commonly affected in peripheral artery disease (PAD). The effects of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor alirocumab added to statin therapy on SFA atherosclerosis, downstream flow, and walking performance are unknown. METHODS: Thirty-five patients with PAD on maximally tolerated statin therapy were recruited. Patients were randomized to alirocumab 150 mg subcutaneously (n = 18) or matching placebo (n = 17) therapy every 2 weeks for 1 year. The primary outcome was change in SFA plaque volume by black blood magnetic resonance imaging (MRI). Secondary outcomes were changes in calf muscle perfusion by cuff/occlusion hyperemia arterial spin labeling MRI, 6-minute walk distance (6MWD), low-density lipoprotein (LDL) cholesterol, and other biomarkers. RESULTS: Age (mean ± SD) was 64 ± 8 years, 20 (57%) patients were women, 17 (49%) were Black individuals, LDL was 107 ± 36 mg/dL, and the ankle-brachial index 0.71 ± 0.20. The LDL fell more with alirocumab than placebo (mean [95% CI]) (-49.8 [-66.1 to -33.6] vs -7.7 [-19.7 to 4.3] mg/dL; p < 0.0001). Changes in SFA plaque volume and calf perfusion showed no difference between groups when adjusted for baseline (+0.25 [-0.29 to 0.79] vs -0.04 [-0.47 to 0.38] cm3; p = 0.37 and 0.22 [-8.67 to 9.11] vs 3.81 [-1.45 to 9.08] mL/min/100 g; p = 0.46, respectively), nor did 6MWD. CONCLUSION: In this exploratory study, the addition of alirocumab therapy to statins did not alter SFA plaque volume, calf perfusion or 6MWD despite significant LDL lowering. Larger studies with longer follow up that include plaque characterization may improve understanding of the effects of intensive LDL-lowering therapy in PAD (ClinicalTrials.gov Identifier: NCT02959047).

Optimal saturation recovery time for minimizing the underestimation of arterial input function in quantitative cardiac perfusion MRI.

PURPOSE: The purpose of this study was to determine an optimal saturation-recovery time (TS) for minimizing the underestimation of arterial input function (AIF) in quantitative cardiac perfusion MRI without multiple gadolinium injections per subject. METHODS: We scanned 18 subjects (mean age = 59 ± 14 years, 9/9 males/females) to acquire resting perfusion data and 1 additional subject (age = 38 years, male) to obtain stress-rest perfusion data using a 5-fold accelerated pulse sequence with radial k-space sampling and applied k-space weighted image contrast (KWIC) filters on the same k-space data to retrospectively reconstruct five AIF images with effective TS ranging from 10 to 21.2 ms (2.8 ms steps). Undersampled images were reconstructed using a compressed sensing framework with temporal-total-variation and temporal-principal-component as 2 orthogonal sparsifying transforms. The image processing steps included, same motion correction across five different AIF images, signal normalization by the proton-density-weighted-image, signal-to-T1 conversion using a Bloch equation, T1 -to-gadolinium-concentration conversion assuming fast water exchange, T2 * correction to the AIF, and gadolinium-concentration to myocardial blood flow (MBF) conversion based on a Fermi model. RESULTS: Among five TS values, the shortest TS (10 ms) produced significantly (P < 0.05) higher peak AIF and lower resting MBF (13.73 mM, 0.73 mL g-1 min-1 ) than 12.8 ms (11.24 mM, 0.89 mL g-1 min-1 ), 15.6 ms (9.56 mM, 1.05 mL g-1 min-1 ), 18.4 ms (8.55 mM, 1.17 mL g-1 min-1 ), and 21.2 ms (7.95 mM, 1.27 mL g-1 min-1 ). Similarly, shorter TS reduced underestimation of AIF (or overestimation of MBF) for both during stress and at rest, but this effect was canceled in myocardial-perfusion-reserve (MPR). CONCLUSION: This study demonstrates that TS of 10 ms reduces the underestimation of AIF and, hence, the overestimation of MBF compared with longer TS values (12.8-21.2 ms).

Aortic Pulse Wave Velocity Evaluated by 4D Flow MRI Across the Adult Lifespan.

BACKGROUND: Evaluation of aortic stiffness by pulse wave velocity (PWV) across the adult lifespan is needed to better understand normal aging in women and men. PURPOSE: To characterize PWV in the thoracic aorta using 4D flow MRI in an age- and sex-stratified cohort of healthy adults. STUDY TYPE: Retrospective. POPULATION: Ninety nine healthy participants (age: 46 ± 15 [19-79] years, 50% female), divided into young adults (<45 years) (N = 48), midlife (45-65 years) (N = 37), and later life (>65 years) (N = 14) groups. FIELD STRENGTH/SEQUENCE: 1.5 T or 3 T, 2D cine bSSFP, 4D flow MRI. ASSESSMENT: Cardiac functional parameters of end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV) and myocardial mass were assessed by 2D cine bSSFP. PWV and aortic blood flow velocity were assessed by 4D flow MRI. Reproducibility of PWV was evaluated in a subset of nine participants. STATISTICAL TESTS: Analysis of variance, Pearson's correlation coefficient (r), linear regression, intraclass correlation coefficient (ICC). A P value < 0.05 was considered statistically significant. RESULTS: PWV increased significantly with age (young adults: 5.4 ± 0.9 m/sec, midlife: 7.2 ± 1.1 m/sec, and later life: 9.4 ± 1.8 m/sec) (r = 0.79, slope = 0.09 m/sec/year). PWV did not differ in women and men in entire sample (P = 0.40) or within age groups (young adults: P = 0.83, midlife: P = 0.17, and later life: P = 0.96). PWV was significantly correlated with EDV (r = -0.29), ESV (r = -0.23), SV (r = -0.28), myocardial mass (r = 0.21), and mean aortic blood flow velocity (r = -0.62). In the test-retest subgroup (N = 9), PWV was 6.7 ± 1.5 [4.4-9.3] m/sec and ICC = 0.75. DATA CONCLUSION: 4D flow MRI quantified higher aortic PWV with age, by approximately 1 m/sec per decade, and significant differences between young adults, midlife and later life. Reproducibility analysis showed good test-retest agreement. Increased PWV was associated with decline in cardiac function and reduced aortic blood flow velocity. This study demonstrates the utility of 4D flow MRI-derived aortic PWV for studying aging. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Evaluation of Pulmonary Hypertension Using 4D Flow MRI.

BACKGROUND: Cardiac magnetic resonance imaging (MRI) is becoming an alternative to right heart catheterization (RHC) for evaluating pulmonary hypertension (PH). A need exists to further evaluate cardiac MRI's ability to characterize PH. PURPOSE: To evaluate the potential for four-dimensional (4D) flow MRI-derived pulmonary artery velocities to characterize PH. STUDY TYPE: Prospective case-control. POPULATION: Fifty-four PH patients (56% female); 25 controls (36% female). FIELD STRENGTH/SEQUENCE: 1.5 T; gradient recalled echo 4D flow and balanced steady-state free precession cardiac cine. ASSESSMENT: RHC was used to derive patients' pulmonary vascular resistance (PVR). 4D flow measured blood velocities at the main, left, and right pulmonary arteries (MPA, LPA, and RPA); cine measured ejection fraction, end diastolic, and end systolic volumes (EF, EDV, and ESV). EDV and ESV were normalized (indexed) to body surface area (ESVI and EDVI). Parameters were evaluated between, and within, PH subgroups: pulmonary arterial hypertension (PAH); PH due to left heart disease (PH-LHD)/chronic lung disease (PH-CLD)/or chronic thrombo-emboli (CTE-PH). STATISTICAL TESTS: Analysis of variance and Kruskal-Wallis tests compared parameters between subgroups. Pearson's r assessed velocity, PVR, and volume correlations. Significance definition: P < 0.05. RESULTS: PAH peak and mean velocities were significantly lower than in controls at the LPA (36 ± 12 cm/second and 20 ± 4 cm/second vs. 59 ± 15 cm/second and 32 ± 9 cm/second). At the RPA, mean velocities were significantly lower in PAH vs. controls (27 ± 6 cm/second vs. 40 ± 9 cm/second). Peak velocities significantly correlated with right ventricular EF at the MPA (r = 0.286), RPA (r = 0.400), and LPA (r = 0.401). Peak velocity significantly correlated with right ventricular ESVI at the RPA (r = -0.355) and LPA (r = -0.316). Significant correlations between peak velocities and PVR were moderate at the LPA in PAH (r = -0.641) and in PH-LHD (r = -0.606) patients, and at the MPA in PH-CLD (r = -0.728). CTE-PH showed non-significant correlations between peak velocity and PVR at all locations. DATA CONCLUSION: Preliminary findings suggest 4D flow can identify PAH and track PVR changes. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 5.

MRA of the Supraaortic Vasculature: Comparison of Gadobutrol and Gadoterate Meglumine at 1.5 T.

BACKGROUND: Gadobutrol (GB) and gadoterate meglumine (GM) are contrast agents used for contrast-enhanced magnetic resonance angiography (CEMRA). Supraaortic vasculature (SAV) CEMRAs are used to evaluate stroke risk and neurologic symptoms. There is a need to compare the SAV CEMRA image quality obtained with GB and GM. PURPOSE: To intra-individually compare MRA images obtained with equimolar GB and GM at 1.5 T in the SAV. STUDY TYPE: Prospective, crossover. POPULATION: Twenty-eight subjects (54 ± 13 years; 17 female). FIELD STRENGTH/SEQUENCE: 1.5 T; three-dimensional (3D) gradient recalled echo. ASSESSMENT: Quantitative image quality was measured by normalized signal intensity (SIn ) [SIn  = SI blood/SD blood] and contrast ratio (CR) [CR = SI blood/SI muscle], determined by an observer (JWC) with 1 year of vascular imaging experience. Three radiologists (AS, PA, and MU) with (5, 5, and 6 years of) vascular imaging experience evaluated image quality by Likert-scale ratings (of image impression, wall conspicuity, and artifact absence). STATISTICAL TESTS: SIn and CR were compared with paired t-tests or Wilcoxon signed-rank tests and Bland-Altman plots. Qualitative ratings were compared with Wilcoxon signed-rank test. RESULTS: No significant difference in SIn was found between GB and GM. CRs with GB were significantly higher than GM at the right common carotid (6.9 ± 2.5 vs. 4.8 ± 1), left internal carotid (7.3 ± 2 vs. 4.4 ± 1.2), right internal carotid (7.7 ± 2.2 vs. 5 ± 1.1), and left vertebral (6.6 ± 2.2 vs. 4.5 ± 1.1) arteries. Bland-Altman plots showed relatively greater differences between GB and GM at higher CRs and SIn s. GM showed significantly higher artifact than GB (3.56 ± 0.52 vs. 3.36 ± 0.46) and significantly lower overall image quality (10.73 ± 1.45 vs. 11.26 ± 1.58) at the left vertebral artery. DATA CONCLUSION: At 1.5 T and equimolar demonstration, GB (0.1 mL/kg, i.e., 0.1 mmol/kg) showed higher CRs in the SAV compared to GM (0.2 mL/kg, i.e., 0.1 mmol/kg) at most vessels. Subjective image quality was not significantly different between the two agents for most vessels. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

A theoretical framework for retrospective T2∗ correction to the arterial input function in quantitative myocardial perfusion MRI.

PURPOSE: To develop and evaluate a flexible, Bloch-equation based framework for retrospective T2∗ correction to the arterial input function (AIF) obtained with quantitative cardiac perfusion pulse sequences. METHODS: Our framework initially calculates the gadolinium concentration [Gd] based on T1 measurements alone. Next, T2∗ is estimated from this initial calculation of [Gd] while assuming fast water exchange and using the literature native T2 and static magnetic field variation (ΔB0 ) values. Finally, the [Gd] is recalculated after performing T2∗ correction to the Bloch equation signal model. Using this approach, we performed T2∗ correction to historical phantom and in vivo, dual-imaging perfusion data sets from 3 different patient groups obtained using different pulse sequences and imaging parameters. Images were processed to quantify both the AIF and resting myocardial blood flow (MBF). We also performed a sensitivity analysis of our T2∗ correction to ±20% variations in native T2 and ΔB0 . RESULTS: Compared with the ground truth [Gd] of phantom, the normalized root-means-square-error (NRMSE) in measured [Gd] was 5.1%, 1.3%, and 0.6% for uncorrected, our corrected, and Kellman's corrected, respectively. For in vivo data, both the peak AIF (7.0 ± 3.0 mM vs. 8.6 ± 7.1 mM, 7.2 ± 0.9 mM vs. 8.6 ± 1.7 mM, 7.7 ± 1.8 mM vs. 10.3 ± 5.1 mM, P < .001) and resting MBF (1.3 ± 0.1 mL/g/min vs. 1.1 ± 0.1 mL/g/min, 1.3 ± 0.1 mL/g/min vs. 1.1 ± 0.1 mL/g/min, 1.2 ± 0.1 mL/g/min vs. 0.9 ± 0.1 mL/g/min, P < .001) values were significantly different between uncorrected and corrected for all 3 patient groups. Both the peak AIF and resting MBF values varied by <5% over the said variations in native T2 and ΔB0 . CONCLUSION: Our theoretical framework enables retrospective T2∗ correction to the AIF obtained with dual-imaging, cardiac perfusion pulse sequences.

Automated segmentation of biventricular contours in tissue phase mapping using deep learning.

Tissue phase mapping (TPM) is an MRI technique for quantification of regional biventricular myocardial velocities. Despite its potential, clinical use is limited due to the requisite labor-intensive manual segmentation of cardiac contours for all time frames. The purpose of this study was to develop a deep learning (DL) network for automated segmentation of TPM images, without significant loss in segmentation and myocardial velocity quantification accuracy compared with manual segmentation. We implemented a multi-channel 3D (three dimensional; 2D + time) dense U-Net that trained on magnitude and phase images and combined cross-entropy, Dice, and Hausdorff distance loss terms to improve the segmentation accuracy and suppress unnatural boundaries. The dense U-Net was trained and tested with 150 multi-slice, multi-phase TPM scans (114 scans for training, 36 for testing) from 99 heart transplant patients (44 females, 1-4 scans/patient), where the magnitude and velocity-encoded (Vx , Vy , Vz ) images were used as input and the corresponding manual segmentation masks were used as reference. The accuracy of DL segmentation was evaluated using quantitative metrics (Dice scores, Hausdorff distance) and linear regression and Bland-Altman analyses on the resulting peak radial and longitudinal velocities (Vr and Vz ). The mean segmentation time was about 2 h per patient for manual and 1.9 ± 0.3 s for DL. Our network produced good accuracy (median Dice = 0.85 for left ventricle (LV), 0.64 for right ventricle (RV), Hausdorff distance = 3.17 pixels) compared with manual segmentation. Peak Vr and Vz measured from manual and DL segmentations were strongly correlated (R ≥ 0.88) and in good agreement with manual analysis (mean difference and limits of agreement for Vz and Vr were -0.05 ± 0.98 cm/s and -0.06 ± 1.18 cm/s for LV, and -0.21 ± 2.33 cm/s and 0.46 ± 4.00 cm/s for RV, respectively). The proposed multi-channel 3D dense U-Net was capable of reducing the segmentation time by 3,600-fold, without significant loss in accuracy in tissue velocity measurements.

Cine MRI detects elevated left heart pressure in pulmonary hypertension.

Cine magnetic resonance imaging (MRI) is an emerging modality for evaluating left ventricular (LV) motion/deformation patterns, which may have potential to identify LV dysfunctions underlying postcapillary pulmonary hypertension (PH). The aim of this study was to test the hypothesis that cine MRI-derived LV motion/deformation indices can be used to identify an elevated left heart pressure in PH. This was a retrospective study, which included 26 precapillary and 28 postcapillary PH patients (23 males, 58.9 ± 13.5 years old). All patients underwent right heart catheterization (the "reference standard") and cardiac MRI. Balanced steady-state free precession cine sequence acquired at 1.5 T was used. Cine MRI datasets were analyzed by using heart deformation analysis. LV motion/deformation indices were measured through 25 phases within a cardiac cycle. Peak LV displacement, velocity, strain, and strain rates at systole, early and late diastole were compared between the two patient groups using t-tests. The Pearson correlation coefficient (r) was used to investigate the association between cine MRI-derived indices and pulmonary capillary wedge pressure (PCWP). Multivariable linear and logistic regression models were applied to assess the ability of MRI-derived parameters to predict PCWP and postcapillary PH. Compared to 26 precapillary PH patients, the 28 postcapillary PH patients had lower peak late radial diastolic displacement (0.43 ± 0.19 cm vs. 0.64 ± 0.18 cm) and velocity (12.2 ± 5.8 mm/s vs. 18.9 ± 5.6 mm/s) and peak late radial (52.1 ± 32.7%/s vs. 97.1 ± 38%/s) and circumferential (38 ± 19.8%/s vs. 63.1 ± 22.9%/s) strain rates. PCWP was correlated with peak late radial diastolic displacement (r = -0.54) and velocity (r = -0.57) and peak late radial (r = -0.63) and circumferential diastolic (r = -0.63) strain rates. Peak late radial strain rate could predict PCWP (ß = -0.09) and postcapillary PH (ß = -0.036). All p < 0.05. Cine MRI-derived LV late diastolic motion/deformation properties can be used to estimate elevated left heart pressure in PH. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 1.

Cardiac MRI Reveals Late Diastolic Changes in Left Ventricular Relaxation Patterns During Healthy Aging.

BACKGROUND: Cardiac MRI is an emerging modality for evaluating left ventricular (LV) diastolic dysfunction (LVDD), a pathological condition that is prevalent in aging populations. However, there is a lack of reports of MRI-derived LV diastolic properties in late diastole. PURPOSE: To test the hypothesis that cine MRI-derived motion/deformation indices can be used to characterize age-related changes on LV relaxation patterns in late diastole. STUDY TYPE: Retrospective. POPULATION: In all, 412 participants (72.5 ± 4.6 years old, range 65-84) without a documented history of cardiovascular diseases. FIELD STRENGTH/SEQUENCE: Balanced steady-state free precession(bSSFP) acquired at 1.5T. ASSESSMENT: Participants were divided into younger (65-74 years old, n = 275) and older (75-84 years old, n = 137) groups. Status of diabetes mellitus (DM), hypertension (HTN), and lipid disorders were recorded for each participant. Cine MRI datasets were analyzed by using heart deformation analysis (HDA). LV motion/deformation indices (displacement, velocity, strain, and strain rate) were measured through 22 phases within a cardiac cycle. STATISTICAL TESTS: The prevalence of traditional cardiovascular risk conditions, LV ejection fraction (LVEF), peak LV regional displacement, velocity, and strain rates at early and late diastole were compared between two participant groups using chi-square tests or t-tests. RESULTS: Older participants had a significantly lower peak early radial displacement (0.797 ± 0.249 cm vs. 0.876 ± 0.286 cm), radial velocity (19.3 ± 6.3 mm/s vs. 17.5 ± 5.2 mm/s), and circumferential strain rate (64.6 ± 15.7%/s vs. 70.1 ± 17%/s) but a higher peak late circumferential strain rate (69.8 ± 16.3 %/s vs. 66 ± 15.8 %/s) than their younger counterparts. DATA CONCLUSION: Cine MRI can be used to characterize age-related LV relaxation patterns in late diastole. LEVEL OF EVIDENCE: 3. TECHNICAL EFFICACY STAGE: 1.

Fibrosis in Hypertrophic Cardiomyopathy Patients With and Without Sarcomere Gene Mutations.

BACKGROUND: Patients with hypertrophic cardiomyopathy (HCM) and an identified sarcomere mutation have worse outcomes than those without though the underlying mechanism is incompletely understood. The presence of replacement fibrosis measured by late gadolinium enhancement (LGE) and diffuse fibrosis measured by extracellular volume (ECV) using cardiac magnetic resonance imaging (CMR) are associated with ventricular arrhythmias and cardiac mortality. We aimed to associate these two forms of fibrosis with identified sarcomere mutations. METHODS AND RESULTS: Three hundred and thirty-six (336) patients with HCM underwent CMR at a single quaternary referral centre between January 2012 and February 2017. Genetic testing was performed in 73 of these patients, yielding an identified sarcomeric mutation in 29 (G+), no mutation in 39 (G-), and a variant of unknown significance (VUS) in five. LGE was more prevalent in G+ compared to G- patients (86 vs. 56%, OR 4.3, p=0.01) and was more extensive (7.5±5.5% of left ventricular [LV] mass vs. 3.0±3.0%, p<0.001). Global ECV from myocardial segments excluding LGE was similar among both groups (26.9±2.9 vs. 25.6±2.8%, p=0.46). However, in G+ patients ECV was greater in the hypertrophied regions of the basal anteroseptum (30.2±7.0 vs. 26.8±3.6%, p=0.004) and basal inferoseptum (28.1±4.3 vs. 26.2±2.9%, p=0.005). CONCLUSIONS: Genotyped HCM patients with an identified sarcomere mutation have greater LGE and greater regional, but not global, ECV than HCM patients without an identified mutation. This difference in fibrosis may contribute to worse outcomes in patients with an identified HCM mutation.

Rapid dealiasing of undersampled, non-Cartesian cardiac perfusion images using U-net.

Compressed sensing (CS) is a promising method for accelerating cardiac perfusion MRI to achieve clinically acceptable image quality with high spatial resolution (1.6 × 1.6 × 8 mm3 ) and extensive myocardial coverage (6-8 slices per heartbeat). A major disadvantage of CS is its relatively lengthy processing time (~8 min per slice with 64 frames using a graphics processing unit), thereby making it impractical for clinical translation. The purpose of this study was to implement and test whether an image reconstruction pipeline including a neural network is capable of reconstructing 6.4-fold accelerated, non-Cartesian (radial) cardiac perfusion k-space data at least 10 times faster than CS, without significant loss in image quality. We implemented a 3D (2D + time) U-Net and trained it with 132 2D + time datasets (coil combined, zero filled as input; CS reconstruction as reference) with 64 time frames from 28 patients (8448 2D images in total). For testing, we used 56 2D + time coil-combined, zero-filled datasets (3584 2D images in total) from 12 different patients as input to our trained U-Net, and compared the resulting images with CS reconstructed images using quantitative metrics of image quality and visual scores (conspicuity of wall enhancement, noise, artifacts; each score ranging from 1 (worst) to 5 (best), with 3 defined as clinically acceptable) evaluated by readers. Including pre- and post-processing steps, compared with CS, U-Net significantly reduced the reconstruction time by 14.4-fold (32.1 ± 1.4 s for U-Net versus 461.3 ± 16.9 s for CS, p < 0.001), while maintaining high data fidelity (structural similarity index = 0.914 ± 0.023, normalized root mean square error = 1.7 ± 0.3%, identical mean edge sharpness of 1.2 mm). The median visual summed score was not significantly different (p = 0.053) between CS (14; interquartile range (IQR) = 0.5) and U-Net (12; IQR = 0.5). This study shows that the proposed pipeline with a U-Net is capable of reconstructing 6.4-fold accelerated, non-Cartesian cardiac perfusion k-space data 14.4 times faster than CS, without significant loss in data fidelity or image quality.

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

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

Effect of Aortic Valve Disease on 3D Hemodynamics in Patients With Aortic Dilation and Trileaflet Aortic Valve Morphology.

BACKGROUND: The effect of different expressions of aortic valve disease on 3D aortic hemodynamics is unclear. PURPOSE: To investigate changes in aortic hemodynamics in patients with dilated ascending aorta (AAo) but different severity of aortic valve stenosis (AS) and/or regurgitation (AR). STUDY TYPE: Retrospective. POPULATION: A total of 111 subjects (86 patients with AAo diameter ≥ 40 mm and 25 healthy controls, all with trileaflet aortic valve [TAV]). Patients were further stratified by TAV dysfunction: n = 9 with combined moderate or severe AS and AR (ASR, 56 ± 13 years), n = 14 with moderate or severe AS (AS, 64 ± 14 years), n = 33 with moderate or severe AR (AR, 62 ± 14 years), n = 30 with neither AS nor AR (no AS/AR, 63 ± 9 years). FIELD STRENGTH/SEQUENCE: 4D flow MRI on 1.5/3T systems for the in vivo analysis of aortic blood flow dynamics. ASSESSMENT: Data analysis included grading of 3D AAo vortex/helix flow and AAo flow eccentricity as well as quantification of systolic peak velocities and wall shear stress (WSS). STATISTICAL TESTS: Continuous variables were compared by one-way analysis of variance or Kruskal-Wallis, followed by a pairwise Tukey or Dunn test if there was a significant difference. RESULTS: All patients demonstrated markedly elevated vortex and helix flow compared with controls (P < 0.05). Peak velocities were significantly elevated in ASR, AS, and AR patients compared with controls (P < 0.05). Increased flow eccentricity was observed in entire AAo for AR, at the mid and distal AAo for ASR and AS, and at the proximal AAo for no AS/AR. Compared with controls, WSS in the AAo was significantly elevated in ASR and AS patients (P < 0.05) and reduced in no AS/AR patients (P < 0.05). DATA CONCLUSION: The presence of TAV dysfunction is associated with aberrant hemodynamics and altered WSS, which may play a role in the development of aortopathy. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2020;51:481-491.

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

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

Parametric Hemodynamic 4D Flow MRI Maps for the Characterization of Chronic Thoracic Descending Aortic Dissection.

BACKGROUND: Systematic evaluation of complex flow in the true lumen and false lumen (TL, FL) is needed to better understand which patients with chronic descending aortic dissection (DAD) are predisposed to complications. PURPOSE: To develop quantitative hemodynamic maps from 4D flow MRI for evaluating TL and FL flow characteristics. STUDY TYPE: Retrospective. POPULATION: In all, 20 DAD patients (age = 60 ± 11 years; 12 male) (six medically managed type B AD [TBAD], 14 repaired type A AD [rTAAD] now with ascending aortic graft [AAo] or elephant trunk [ET1] repair) and 21 age-matched controls (age = 59 ± 10 years; 13 male) were included. FIELD STRENGTH/SEQUENCE: 1.5T, 3T, 4D flow MRI. ASSESSMENT: 4D flow MRI was acquired in all subjects. Data analysis included 3D segmentation of TL and FL and voxelwise calculation of forward flow, reverse flow, flow stasis, and kinetic energy as quantitative hemodynamics maps. STATISTICAL TESTS: Analysis of variance (ANOVA) or Kruskal-Wallis tests were performed for comparing subject groups. Correlation and Bland-Altman analysis was performed for the interobserver study. RESULTS: Patients with rTAAD presented with elevated TL reverse flow (AAo repair: P = 0.004, ET1: P = 0.018) and increased TL kinetic energy (AAo repair: P = 0.0002, ET1: P = 0.011) compared to controls. In addition, TL kinetic energy was increased vs. patients with TBAD (AAo repair: P = 0.021, ET1: P = 0.048). rTAAD was associated with higher FL kinetic energy and lower FL stasis compared to patients with TBAD (AAo repair: P = 0.002, ET1: P = 0.024 and AAo repair: P = 0.003, ET1: P = 0.048, respectively). DATA CONCLUSION: Quantitative maps from 4D flow MRI demonstrated global and regional hemodynamic differences between DAD patients and controls. Patients with rTAAD vs. TBAD had significantly altered regional TL and FL hemodynamics. These findings indicate the potential of 4D flow MRI-derived hemodynamic maps to help better evaluate patients with DAD. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2020;51:1357-1368.

Cost-effectiveness of lung MRI in lung cancer screening.

OBJECTIVES: Recent studies with lung MRI (MRI) have shown high sensitivity (Sn) and specificity (Sp) for lung nodule detection and characterization relative to low-dose CT (LDCT). Using this background data, we sought to compare the potential screening performance of MRI vs. LDCT using a Markov model of lung cancer screening. METHODS: We created a Markov cohort model of lung cancer screening which incorporated lung cancer incidence, progression, and mortality based on gender, age, and smoking burden. Sensitivity (Sn) and Sp for LDCT were taken from the MISCAN Lung Microsimulation and Sn/Sp for MRI was estimated from a published substudy of the German Lung Cancer Screening and Intervention Trial. Screening, work-up, and treatment costs were estimated from published data. Screening with MRI and LDCT was simulated for a cohort of male and female smokers (2 packs per day; 36 pack/years of smoking history) starting at age 60. We calculated the screening performance and cost-effectiveness of MRI screening and performed a sensitivity analysis on MRI Sn/Sp and cost. RESULTS: There was no difference in life expectancy between MRI and LDCT screening (males 13.28 vs. 13.29 life-years; females 14.22 vs. 14.22 life-years). MRI had a favorable cost-effectiveness ratio of $258,169 in men and $403,888 in women driven by fewer false-positive screens. On sensitivity analysis, MRI remained cost effective at screening costs < $396 dollars and Sp > 81%. CONCLUSIONS: In this Markov model of lung cancer screening, MRI has a near-equivalent life expectancy benefit and has superior cost-effectiveness relative to LDCT. KEY POINTS: • In this Markov model of lung cancer screening, there is no difference in mortality between yearly screening with MRI and low-dose CT. • Compared to low-dose CT, screening with MRI led to a reduction in false-positive studies from 26 to 2.8% in men and 26 to 2.6% in women. • Due to similar life-expectancy and reduced false-positive rate, we found a favorable cost-effectiveness ratio of $258,169 in men and $403,888 in women of MRI relative to low-dose CT.

Society for Cardiovascular Magnetic Resonance (SCMR) guidance for re-activation of cardiovascular magnetic resonance practice after peak phase of the COVID-19 pandemic.

During the peak phase of the COVID-19 pandemic, alterations of standard operating procedures were necessary for health systems to protect patients and healthcare workers and ensure access to vital hospital resources. As the peak phase passes, re-activation plans are required to safely manage increasing clinical volumes. In the context of cardiovascular magnetic resonance (CMR), re-activation objectives include continued performance of urgent CMR studies and resumption of CMR in patients with semi-urgent and elective indications in an environment that is safe for both patients and health care workers.