Pre-excitation gradients for eddy current nulled convex optimized diffusion encoding (Pre-ENCODE).

PURPOSE: To evaluate the use of pre-excitation gradients for eddy current-nulled convex optimized diffusion encoding (Pre-ENCODE) to mitigate eddy current-induced image distortions in diffusion-weighted MRI (DWI). METHODS: DWI sequences using monopolar (MONO), ENCODE, and Pre-ENCODE were evaluated in terms of the minimum achievable echo time (TE min $$ {}_{\mathrm{min}} $$ ) and eddy current-induced image distortions using simulations, phantom experiments, and in vivo DWI in volunteers ( N = 6 $$ N=6 $$ ). RESULTS: Pre-ENCODE provided a shorter TE min $$ {}_{\mathrm{min}} $$ than MONO (71.0 ± $$ \pm $$ 17.7ms vs. 77.6 ± $$ \pm $$ 22.9ms) and ENCODE (71.0 ± $$ \pm $$ 17.7ms vs. 86.2 ± $$ \pm $$ 14.2ms) in 100 % $$ \% $$ of the simulated cases for a commercial 3T MRI system with b-values ranging from 500 to 3000 s/mm 2 $$ {}^2 $$ and in-plane spatial resolutions ranging from 1.0 to 3.0mm 2 $$ {}^2 $$ . Image distortion was estimated by intravoxel signal variance between diffusion encoding directions near the phantom edges and was significantly lower with Pre-ENCODE than with MONO (10.1 % $$ \% $$ vs. 22.7 % $$ \% $$ , p = 6 - 5 $$ p={6}^{-5} $$ ) and comparable to ENCODE (10.1 % $$ \% $$ vs. 10.4 % $$ \% $$ , p = 0 . 12 $$ p=0.12 $$ ). In vivo measurements of apparent diffusion coefficients were similar in global brain pixels (0.37 [0.28,1.45] × 1 0 - 3 $$ \times 1{0}^{-3} $$ mm 2 $$ {}^2 $$ /s vs. 0.38 [0.28,1.45] × 1 0 - 3 $$ \times 1{0}^{-3} $$ mm 2 $$ {}^2 $$ /s, p = 0 . 25 $$ p=0.25 $$ ) and increased in edge brain pixels (0.80 [0.17,1.49] × 1 0 - 3 $$ \times 1{0}^{-3} $$ mm 2 $$ {}^2 $$ /s vs. 0.70 [0.18,1.48] × 1 0 - 3 $$ \times 1{0}^{-3} $$ mm 2 $$ {}^2 $$ /s, p = 0 . 02 $$ p=0.02 $$ ) for MONO compared to Pre-ENCODE. CONCLUSION: Pre-ENCODE mitigated eddy current-induced image distortions for diffusion imaging with a shorter TE min $$ {}_{\mathrm{min}} $$ than MONO and ENCODE.

SCMR expert consensus statement for cardiovascular magnetic resonance of patients with a cardiac implantable electronic device.

Cardiovascular magnetic resonance (CMR) is a proven imaging modality for informing diagnosis and prognosis, guiding therapeutic decisions, and risk stratifying surgical intervention. Patients with a cardiac implantable electronic device (CIED) would be expected to derive particular benefit from CMR given high prevalence of cardiomyopathy and arrhythmia. While several guidelines have been published over the last 16 years, it is important to recognize that both the CIED and CMR technologies, as well as our knowledge in MR safety, have evolved rapidly during that period. Given increasing utilization of CIED over the past decades, there is an unmet need to establish a consensus statement that integrates latest evidence concerning MR safety and CIED and CMR technologies. While experienced centers currently perform CMR in CIED patients, broad availability of CMR in this population is lacking, partially due to limited availability of resources for programming devices and appropriate monitoring, but also related to knowledge gaps regarding the risk-benefit ratio of CMR in this growing population. To address the knowledge gaps, this SCMR Expert Consensus Statement integrates consensus guidelines, primary data, and opinions from experts across disparate fields towards the shared goal of informing evidenced-based decision-making regarding the risk-benefit ratio of CMR for patients with CIEDs.

Accelerated two-dimensional phase-contrast for cardiovascular MRI using deep learning-based reconstruction with complex difference estimation.

PURPOSE: To develop and validate a deep learning-based reconstruction framework for highly accelerated two-dimensional (2D) phase contrast (PC-MRI) data with accurate and precise quantitative measurements. METHODS: We propose a modified DL-ESPIRiT reconstruction framework for 2D PC-MRI, comprised of an unrolled neural network architecture with a Complex Difference estimation (CD-DL). CD-DL was trained on 155 fully sampled 2D PC-MRI pediatric clinical datasets. The fully sampled data ( n = 29 $$ n=29 $$ ) was retrospectively undersampled (6-11 × $$ \times $$ ) and reconstructed using CD-DL and a parallel imaging and compressed sensing method (PICS). Measurements of peak velocity and total flow were compared to determine the highest acceleration rate that provided accuracy and precision within ± 5 % $$ \pm 5\% $$ . Feasibility of CD-DL was demonstrated on prospectively undersampled datasets acquired in pediatric clinical patients ( n = 5 $$ n=5 $$ ) and compared to traditional parallel imaging (PI) and PICS. RESULTS: The retrospective evaluation showed that 9 × $$ \times $$ accelerated 2D PC-MRI images reconstructed with CD-DL provided accuracy and precision (bias, [95 % $$ \% $$ confidence intervals]) within ± 5 % $$ \pm 5\% $$ . CD-DL showed higher accuracy and precision compared to PICS for measurements of peak velocity (2.8 % $$ \% $$ [ - 2 . 9 $$ -2.9 $$ , 4.5] vs. 3.9 % $$ \% $$ [ - 11 . 0 $$ -11.0 $$ , 4.9]) and total flow (1.8 % $$ \% $$ [ - 3 . 9 $$ -3.9 $$ , 3.4] vs. 2.9 % $$ \% $$ [ - 7 . 1 $$ -7.1 $$ , 6.9]). The prospective feasibility study showed that CD-DL provided higher accuracy and precision than PICS for measurements of peak velocity and total flow. CONCLUSION: In a retrospective evaluation, CD-DL produced quantitative measurements of 2D PC-MRI peak velocity and total flow with ≤ 5 % $$ \le 5\% $$ error in both accuracy and precision for up to 9 × $$ \times $$ acceleration. Clinical feasibility was demonstrated using a prospective clinical deployment of our 8 × $$ \times $$ undersampled acquisition and CD-DL reconstruction in a cohort of pediatric patients.

CanVasc consensus recommendations for the use of avacopan in antineutrophil cytoplasm antibody-associated vasculitis: 2022 addendum.

OBJECTIVE: In 2020, the Canadian Vasculitis Research Network (CanVasc) published their updated recommendations for the management of ANCA-associated vasculitides (AAV). The current addendum provides further recommendations regarding the use of avacopan in AAV based on a review of newly available evidence. METHODS: An updated systematic literature review on avacopan (formerly, CCX168) using Medline, Embase, and the Cochrane Library was performed for publications up to September 2022. New recommendations were developed and categorized according to the EULAR grading levels, as done for previous CanVasc recommendations. A modified Delphi procedure and videoconferences were used to reach ≥80% consensus on the inclusion, wording and grading of each recommendation. RESULTS: Three new recommendations were developed. They focus on avacopan therapy indication and duration, as well as timely glucocorticoid tapering. CONCLUSION: These 2022 addended recommendations provide rheumatologists, nephrologists and other specialists caring for patients with AAV with guidance for the use of avacopan, based on current evidence and consensus from Canadian experts.

Multishot Diffusion-Weighted MRI of the Breasts in the Supine vs. Prone Position.

BACKGROUND: Diffusion-weighted imaging (DWI) may allow for breast cancer screening MRI without a contrast injection. Multishot methods improve prone DWI of the breasts but face different challenges in the supine position. PURPOSE: To establish a multishot DWI (msDWI) protocol for supine breast MRI and to evaluate the performance of supine vs. prone msDWI. STUDY TYPE: Prospective. POPULATION: Protocol optimization: 10 healthy women (ages 22-56), supine vs. prone: 24 healthy women (ages 22-62) and five women (ages 29-61) with breast tumors. FIELD STRENGTH/SEQUENCE: 3-T, protocol optimization msDWI: free-breathing (FB) 2-shots, FB 4-shots, respiratory-triggered (RT) 2-shots, RT 4-shots, supine vs. prone: RT 4-shot msDWI, T2-weighted fast-spin echo. ASSESSMENT: Protocol optimization and supine vs. prone: three observers performed an image quality assessment of sharpness, aliasing, distortion (vs. T2), perceived SNR, and overall image quality (scale of 1-5). Apparent diffusion coefficients (ADCs) in fibroglandular tissue (FGT) and breast tumors were measured. STATISTICAL TESTS: Effect of study variables on dichotomized ratings (4/5 vs. 1/2/3) and FGT ADCs were assessed with mixed-effects logistic regression. Interobserver agreement utilized Gwet's agreement coefficient (AC). Lesion ADCs were assessed by Bland-Altman analysis and concordance correlation (ρc ). P value <0.05 was considered statistically significant. RESULTS: Protocol optimization: 4-shots significantly improved sharpness and distortion; RT significantly improved sharpness, aliasing, perceived SNR, and overall image quality. FGT ADCs were not significantly different between shots (P = 0.812), FB vs. RT (P = 0.591), or side (P = 0.574). Supine vs. prone: supine images were rated significantly higher for sharpness, aliasing, and overall image quality. FGT ADCs were significantly higher supine; lesion ADCs were highly correlated (ρc  = 0.92). DATA CONCLUSION: Based on image quality, supine msDWI outperformed prone msDWI. Lesion ADCs were highly correlated between the two positions, while FGT ADCs were higher in the supine position. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 1.

Myocardial mesostructure and mesofunction.

The complex and highly organized structural arrangement of some five billion cardiomyocytes directs the coordinated electrical activity and mechanical contraction of the human heart. The characteristic transmural change in cardiomyocyte orientation underlies base-to-apex shortening, circumferential shortening, and left ventricular torsion during contraction. Individual cardiomyocytes shorten ∼15% and increase in diameter ∼8%. Remarkably, however, the left ventricular wall thickens by up to 30-40%. To accommodate this, the myocardium must undergo significant structural rearrangement during contraction. At the mesoscale, collections of cardiomyocytes are organized into sheetlets, and sheetlet shear is the fundamental mechanism of rearrangement that produces wall thickening. Herein, we review the histological and physiological studies of myocardial mesostructure that have established the sheetlet shear model of wall thickening. Recent developments in tissue clearing techniques allow for imaging of whole hearts at the cellular scale, whereas magnetic resonance imaging (MRI) and computed tomography (CT) can image the myocardium at the mesoscale (100 µm to 1 mm) to resolve cardiomyocyte orientation and organization. Through histology, cardiac diffusion tensor imaging (DTI), and other modalities, mesostructural sheetlets have been confirmed in both animal and human hearts. Recent in vivo cardiac DTI methods have measured reorientation of sheetlets during the cardiac cycle. We also examine the role of pathological cardiac remodeling on sheetlet organization and reorientation, and the impact this has on ventricular function and dysfunction. We also review the unresolved mesostructural questions and challenges that may direct future work in the field.

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.

Reproducibility of global and segmental myocardial strain using cine DENSE at 3 T: a multicenter cardiovascular magnetic resonance study in healthy subjects and patients with heart disease.

BACKGROUND: While multiple cardiovascular magnetic resonance (CMR) methods provide excellent reproducibility of global circumferential and global longitudinal strain, achieving highly reproducible segmental strain is more challenging. Previous single-center studies have demonstrated excellent reproducibility of displacement encoding with stimulated echoes (DENSE) segmental circumferential strain. The present study evaluated the reproducibility of DENSE for measurement of whole-slice or global circumferential (Ecc), longitudinal (Ell) and radial (Err) strain, torsion, and segmental Ecc at multiple centers. METHODS: Six centers participated and a total of 81 subjects were studied, including 60 healthy subjects and 21 patients with various types of heart disease. CMR utilized 3 T scanners, and cine DENSE images were acquired in three short-axis planes and in the four-chamber long-axis view. During one imaging session, each subject underwent two separate DENSE scans to assess inter-scan reproducibility. Each subject was taken out of the scanner and repositioned between the scans. Intra-user, inter-user-same-site, inter-user-different-site, and inter-user-Human-Deep-Learning (DL) comparisons assessed the reproducibility of different users analyzing the same data. Inter-scan comparisons assessed the reproducibility of DENSE from scan to scan. The reproducibility of whole-slice or global Ecc, Ell and Err, torsion, and segmental Ecc were quantified using Bland-Altman analysis, the coefficient of variation (CV), and the intraclass correlation coefficient (ICC). CV was considered excellent for CV ≤ 10%, good for 10% < CV ≤ 20%, fair for 20% < CV ≤ 40%, and poor for CV > 40. ICC values were considered excellent for ICC > 0.74, good for ICC 0.6 < ICC ≤ 0.74, fair for ICC 0.4 < ICC ≤ 0.59, poor for ICC < 0.4. RESULTS: Based on CV and ICC, segmental Ecc provided excellent intra-user, inter-user-same-site, inter-user-different-site, inter-user-Human-DL reproducibility and good-excellent inter-scan reproducibility. Whole-slice Ecc and global Ell provided excellent intra-user, inter-user-same-site, inter-user-different-site, inter-user-Human-DL and inter-scan reproducibility. The reproducibility of torsion was good-excellent for all comparisons. For whole-slice Err, CV was in the fair-good range, and ICC was in the good-excellent range. CONCLUSIONS: Multicenter data show that 3 T CMR DENSE provides highly reproducible whole-slice and segmental Ecc, global Ell, and torsion measurements in healthy subjects and heart disease patients.

4D flow cardiovascular magnetic resonance recovery profiles following pulmonary endarterectomy in chronic thromboembolic pulmonary hypertension.

BACKGROUND: Four-dimensional flow cardiovascular magnetic resonance imaging (4D flow CMR) allows comprehensive assessment of pulmonary artery (PA) flow dynamics. Few studies have characterized longitudinal changes in pulmonary flow dynamics and right ventricular (RV) recovery following a pulmonary endarterectomy (PEA) for patients with chronic thromboembolic pulmonary hypertension (CTEPH). This can provide novel insights of RV and PA dynamics during recovery. We investigated the longitudinal trajectory of 4D flow metrics following a PEA including velocity, vorticity, helicity, and PA vessel wall stiffness. METHODS: Twenty patients with CTEPH underwent pre-PEA and > 6 months post-PEA CMR imaging including 4D flow CMR; right heart catheter measurements were performed in 18 of these patients. We developed a semi-automated pipeline to extract integrated 4D flow-derived main, left, and right PA (MPA, LPA, RPA) volumes, velocity flow profiles, and secondary flow profiles. We focused on secondary flow metrics of vorticity, volume fraction of positive helicity (clockwise rotation), and the helical flow index (HFI) that measures helicity intensity. RESULTS: Mean PA pressures (mPAP), total pulmonary resistance (TPR), and normalized RV end-systolic volume (RVESV) decreased significantly post-PEA (P < 0.002). 4D flow-derived PA volumes decreased (P < 0.001) and stiffness, velocity, and vorticity increased (P < 0.01) post-PEA. Longitudinal improvements from pre- to post-PEA in mPAP were associated with longitudinal decreases in MPA area (r = 0.68, P = 0.002). Longitudinal improvements in TPR were associated with longitudinal increases in the maximum RPA HFI (r=-0.85, P < 0.001). Longitudinal improvements in RVESV were associated with longitudinal decreases in MPA fraction of positive helicity (r = 0.75, P = 0.003) and minimum MPA HFI (r=-0.72, P = 0.005). CONCLUSION: We developed a semi-automated pipeline for analyzing 4D flow metrics of vessel stiffness and flow profiles. PEA was associated with changes in 4D flow metrics of PA flow profiles and vessel stiffness. Longitudinal analysis revealed that PA helicity was associated with pulmonary remodeling and RV reverse remodeling following a PEA.

Preexisting autoimmune disease and immune-related adverse events associated with anti-PD-1 cancer immunotherapy: a national case series from the Canadian Research Group of Rheumatology in Immuno-Oncology.

BACKGROUND: Limited data are available on the safety and efficacy of immune checkpoint inhibitors (ICI) in patients with preexisting autoimmune diseases (PAD). METHODS: Retrospective study of patients with PAD referred for rheumatologic evaluation prior to starting or during immunotherapy between January 2013 and July 2019 from 10 academic sites across Canada. Data were extracted by chart review using a standardized form. RESULTS: Twenty-seven patients with PAD on ICI therapy were identified. The most common PADs were rheumatoid arthritis (30%), psoriasis/psoriatic arthritis (30%), inflammatory bowel disease (IBD, 15%) and axial spondyloarthritis (11%), and the most frequently observed cancers were lung cancer and melanoma. All patients received anti-PD-1 therapies, and 2 received additional sequential anti-CTLA-4 therapy. PAD exacerbations occurred in 52% over a median (IQR) follow-up of 11.0 (6.0-17.5) months, with 14% being severe, 57% requiring corticosteroids, 50% requiring immunosuppression and 14% requiring ICI discontinuation. Flares were generally more frequent and severe in patients who previously required more intensive immunosuppression (i.e., biologics). Flares occurred despite background immunosuppression at the time of ICI initiation. In patients with preexisting psoriasis, IBD and axial spondyloarthritis, rheumatic immune-related adverse events (irAEs), mostly polyarthritis and tenosynovitis, were frequently observed. Tumor progression was not associated with exposure to immunosuppressive drugs before or after ICI initiation and was numerically less frequent in patients with irAEs. CONCLUSION: PAD exacerbations in the context of ICI treatment are common, although generally mild, and occur despite background immunosuppression. Exacerbations are more frequent and severe in patients on more intensive immunosuppressive therapies pre-immunotherapy.

Myofiber strain in healthy humans using DENSE and cDTI.

PURPOSE: Myofiber strain, Eff , is a mechanistically relevant metric of cardiac cell shortening and is expected to be spatially uniform in healthy populations, making it a prime candidate for the evaluation of local cardiomyocyte contractility. In this study, a new, efficient pipeline was proposed to combine microstructural cDTI and functional DENSE data in order to estimate Eff in vivo. METHODS: Thirty healthy volunteers were scanned with three long-axis (LA) and three short-axis (SA) DENSE slices using 2D displacement encoding and one SA slice of cDTI. The total acquisition time was 11 minutes ± 3 minutes across volunteers. The pipeline first generates 3D SA displacements from all DENSE slices which are then combined with cDTI data to generate a cine of myofiber orientations and compute Eff . The precision of the post-processing pipeline was assessed using a computational phantom study. Transmural myofiber strain was compared to circumferential strain, Ecc , in healthy volunteers using a Wilcoxon sign rank test. RESULTS: In vivo, computed Eff was found uniform transmurally compared to Ecc (-0.14[-0.15, -0.12] vs -0.18 [-0.20, -0.16], P < .001, -0.14 [-0.16, -0.12] vs -0.16 [-0.17, -0.13], P < .001 and -0.14 [-0.16, -0.12] vs Ecc_C = -0.14 [-0.15, -0.11], P = .002, Eff_C vs Ecc_C in the endo, mid, and epi layers, respectively). CONCLUSION: We demonstrate that it is possible to measure in vivo myofiber strain in a healthy human population in 10 minutes per subject. Myofiber strain was observed to be spatially uniform in healthy volunteers making it a potential biomarker for the evaluation of local cardiomyocyte contractility in assessing cardiovascular dysfunction.

Right Ventricular Function and T1-Mapping in Boys With Duchenne Muscular Dystrophy.

BACKGROUND: Clinical management of boys with Duchenne muscular dystrophy (DMD) relies on in-depth understanding of cardiac involvement, but right ventricular (RV) structural and functional remodeling remains understudied. PURPOSE: To evaluate several analysis methods and identify the most reliable one to measure RV pre- and postcontrast T1 (RV-T1) and to characterize myocardial remodeling in the RV of boys with DMD. STUDY TYPE: Prospective. POPULATION: Boys with DMD (N = 27) and age-/sex-matched healthy controls (N = 17) from two sites. FIELD STRENGTH/SEQUENCE: 3.0 T using balanced steady state free precession, motion-corrected phase sensitive inversion recovery and modified Look-Locker inversion recovery sequences. ASSESSMENT: Biventricular mass (Mi), end-diastolic volume (EDVi) and ejection fraction (EF) assessment, tricuspid annular excursion (TAE), late gadolinium enhancement (LGE), pre- and postcontrast myocardial T1 maps. The RV-T1 reliability was assessed by three observers in four different RV regions of interest (ROI) using intraclass correlation (ICC). STATISTICAL TESTS: The Wilcoxon rank sum test was used to compare RV-T1 differences between DMD boys with negative LGE(-) or positive LGE(+) and healthy controls. Additionally, correlation of precontrast RV-T1 with functional measures was performed. A P-value <0.05 was considered statistically significant. RESULTS: A 1-pixel thick RV circumferential ROI proved most reliable (ICC > 0.91) for assessing RV-T1. Precontrast RV-T1 was significantly higher in boys with DMD compared to controls. Both LGE(-) and LGE(+) boys had significantly elevated precontrast RV-T1 compared to controls (1543 [1489-1597] msec and 1550 [1402-1699] msec vs. 1436 [1399-1473] msec, respectively). Compared to healthy controls, boys with DMD had preserved RVEF (51.8 [9.9]% vs. 54.2 [7.2]%, P = 0.31) and significantly reduced RVMi (29.8 [9.7] g vs. 48.0 [15.7] g), RVEDVi (69.8 [29.7] mL/m2 vs. 89.1 [21.9] mL/m2 ), and TAE (22.0 [3.2] cm vs. 26.0 [4.7] cm). Significant correlations were found between precontrast RV-T1 and RVEF (ß = -0.48%/msec) and between LV-T1 and LVEF (ß = -0.51%/msec). DATA CONCLUSION: Precontrast RV-T1 is elevated in boys with DMD compared to healthy controls and is negatively correlated with RVEF. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

Fully-automated global and segmental strain analysis of DENSE cardiovascular magnetic resonance using deep learning for segmentation and phase unwrapping.

BACKGROUND: Cardiovascular magnetic resonance (CMR) cine displacement encoding with stimulated echoes (DENSE) measures heart motion by encoding myocardial displacement into the signal phase, facilitating high accuracy and reproducibility of global and segmental myocardial strain and providing benefits in clinical performance. While conventional methods for strain analysis of DENSE images are faster than those for myocardial tagging, they still require manual user assistance. The present study developed and evaluated deep learning methods for fully-automatic DENSE strain analysis. METHODS: Convolutional neural networks (CNNs) were developed and trained to (a) identify the left-ventricular (LV) epicardial and endocardial borders, (b) identify the anterior right-ventricular (RV)-LV insertion point, and (c) perform phase unwrapping. Subsequent conventional automatic steps were employed to compute strain. The networks were trained using 12,415 short-axis DENSE images from 45 healthy subjects and 19 heart disease patients and were tested using 10,510 images from 25 healthy subjects and 19 patients. Each individual CNN was evaluated, and the end-to-end fully-automatic deep learning pipeline was compared to conventional user-assisted DENSE analysis using linear correlation and Bland Altman analysis of circumferential strain. RESULTS: LV myocardial segmentation U-Nets achieved a DICE similarity coefficient of 0.87 ± 0.04, a Hausdorff distance of 2.7 ± 1.0 pixels, and a mean surface distance of 0.41 ± 0.29 pixels in comparison with manual LV myocardial segmentation by an expert. The anterior RV-LV insertion point was detected within 1.38 ± 0.9 pixels compared to manually annotated data. The phase-unwrapping U-Net had similar or lower mean squared error vs. ground-truth data compared to the conventional path-following method for images with typical signal-to-noise ratio (SNR) or low SNR (p < 0.05), respectively. Bland-Altman analyses showed biases of 0.00 ± 0.03 and limits of agreement of - 0.04 to 0.05 or better for deep learning-based fully-automatic global and segmental end-systolic circumferential strain vs. conventional user-assisted methods. CONCLUSIONS: Deep learning enables fully-automatic global and segmental circumferential strain analysis of DENSE CMR providing excellent agreement with conventional user-assisted methods. Deep learning-based automatic strain analysis may facilitate greater clinical use of DENSE for the quantification of global and segmental strain in patients with cardiac disease.

Assessment of glucocorticoid tapering in large vessel and anti-neutrophil cytoplasmic antibody-associated vasculitides.

OBJECTIVES: Glucocorticoids (GC) remain integral to large vessel vasculitis (LVV) and ANCA-associated vasculitis (AAV) treatment. We aimed to assess real-world GC tapering trajectories among patients referred for LVV or AAV and identify factors associated with 'delayed' tapering. METHODS: Patients first assessed at a vasculitis clinic July 2017-August 2019 for LVV or AAV and taking GC were included. Delayed tapering was defined as prednisone >10 mg above target based on tapering recommendations (2010 British Society of Rheumatology Guidelines for Giant Cell Arteritis, 2015 CanVasc AAV Recommendations). We compared characteristics of patients with delayed and appropriate tapering and assessed barriers to timely tapering though chart reviews and referring physician surveys. RESULTS: 160 patients (65 LVV, 95 AAV) were taking GC at their first visit. Among the 42 (26%) patients with delayed tapering, mean daily prednisone dose was 39.2 mg (SD 14) compared to a target of 15.2 mg (SD 15). Pulse GC were administered to 19/42 (45%) patients with delayed tapering compared to 26/118 (22%) with appropriate tapering (p<0.05). Mean Birmingham Vasculitis Activity Score at treatment onset and GC duration were not significantly different between the two groups. Vision loss and/or stroke was more frequent in LVV referrals who experienced delayed (9/21, 43%) vs. appropriate (6/44, 14%) tapering (p<0.05). Managing risk of vasculitis flare was the most common challenge to tapering GC among surveyed referring physicians. CONCLUSIONS: In one quarter of patients referred for LVV or AAV taking GC, tapering was slower than recommended. Promoting timely tapering may reduce GC toxicity.

An Initiative to Improve Timely Glucocorticoid Tapering in Vasculitis.

BACKGROUND/OBJECTIVE: High-dose glucocorticoids (GCs) are required in the initial treatment of systemic vasculitis. However, slow or delayed tapering can lead to unnecessary GC exposure and toxicity. In this quality improvement initiative, we aimed to increase appropriate GC tapering among newly referred patients awaiting specialty consultation at a tertiary vasculitis clinic. METHODS: For each patient referred for anti-neutrophil cytoplasm antibody-associated vasculitis (AAV) or large vessel vasculitis (LVV), recommendation-based GC tapering suggestions were faxed to referring physicians. To maximize uptake, the intervention format was modified according to feedback from referring physicians' offices. The proportion of new patients presenting to their first appointment who (1) had started to taper GCs, (2) were taking their target GC dose according to recommendations, (3) experienced a vasculitis flare during tapering were compared before (July 2017-January 2019) and after (February-October 2019) the intervention. RESULTS: Among 169 consecutive patients referred for AAV or LVV, the proportion who had started to taper GCs by their first visit increased from 84 of 117 (72%) preintervention to 49 of 52 (94%) postintervention (p < 0.01). Mean daily prednisone dose at first visit decreased from 29.9 (SD, 18) mg to 21.7 (SD, 14) mg (p < 0.01). However, the proportion who were ultimately taking "target" GC doses at their first visit did not significantly increase (72% vs. 77%). Disease flares during tapering were similar before and after the intervention (9% vs. 12%). CONCLUSIONS: Patients with AAV and LVV had increased GC tapering and lower GC doses at first visit following a preappointment intervention. Further strategies are needed to improve timely GC tapering in vasculitis.

A gradient optimization toolbox for general purpose time-optimal MRI gradient waveform design.

PURPOSE: To introduce and demonstrate a software library for time-optimal gradient waveform optimization with a wide range of applications. The software enables direct on-the-fly gradient waveform design on the scanner hardware for multiple vendors. METHODS: The open-source gradient optimization (GrOpt) toolbox was implemented in C with both Matlab and Python wrappers. The toolbox enables gradient waveforms to be generated based on a set of constraints that define the features and encodings for a given acquisition. The GrOpt optimization routine is based on the alternating direction method of multipliers (ADMM). Additional constraints enable error corrections to be added, or patient comfort and safety to be adressed. A range of applications and compute speed metrics are analyzed. Finally, the method is implemented and tested on scanners from different vendors. RESULTS: Time-optimal gradient waveforms for different pulse sequences and the constraints that define them are shown. Additionally, the ability to add, arbitrary motion (gradient moment) compensation or limit peripheral nerve stimulation is demonstrated. There exists a trade-off between computation time and gradient raster time, but it was observed that acceptable gradient waveforms could be generated in 1-40 ms. Gradient waveforms generated and run on the different scanners were functionally equivalent, and the images were comparable. CONCLUSIONS: GrOpt is an open source toolbox that enables on-the-fly optimization of gradient waveform design, subject to a set of defined constraints. GrOpt was presented for a range of imaging applications, analyzed in terms of computational complexity, and implemented to run on the scanner for a multi-vendor demonstration.

Optimization methods for magnetic resonance imaging gradient waveform design.

The development and implementation of novel MRI pulse sequences remains challenging and laborious. Gradient waveforms are typically designed using a combination of analytical and ad hoc methods to construct each gradient waveform axis independently. This strategy makes coding the pulse sequence complicated, in addition to being time inefficient. As a consequence, nearly all commercial MRI pulse sequences fail to maximize use of the available gradient hardware or efficiently mitigate physiological effects. This results in expensive MRI systems that underperform relative to their inherent hardware capabilities. To address this problem, a software solution is proposed that incorporates numerical optimization methods into MRI pulse sequence programming. Examples are shown for rotational variant vs. invariant waveform designs, acceleration nulled velocity encoding gradients, and mitigation of peripheral nerve stimulation for diffusion encoding. The application of optimization methods to MRI pulse sequence design incorporates gradient hardware limits and the prescribed MRI protocol parameters (e.g. field-of-view, resolution, gradient moments, and/or b-value) to simultaneously construct time-optimal gradient waveforms. In many cases, the resulting constrained gradient waveform design problem is convex and can be solved on-the-fly on the MRI scanner. The result is a set of multi-axis time-optimal gradient waveforms that satisfy the design constraints, thereby increasing SNR-efficiency. These optimization methods can also be used to mitigate imaging artifacts (e.g. eddy currents) or account for peripheral nerve stimulation. The result of the optimization method is to enable easier pulse sequence gradient waveform design and permit on-the-fly implementation for a range of MRI pulse sequences.

Evaluation of a Workflow to Define Low Specific Absorption Rate MRI Protocols for Patients With Active Implantable Medical Devices.

BACKGROUND: MRI exams for patients with MR-conditional active implantable medical devices (AIMDs) are contraindicated unless specific conditions are met. This limits the maximum specific absorption rate (SAR, W/kg). Currently, there is no general framework to guide meeting a lower SAR limit. PURPOSE: To design and evaluate a workflow for modifying MRI protocols to whole-body SAR (WB-SAR ≤0.1 W/kg) and local-head SAR (LH-SAR ≤0.3 W/kg) limits while mitigating the impact on image quality and exam time. STUDY TYPE: Prospective. POPULATION: Twenty healthy volunteers on head (n = 5), C-spine (n = 5), T-spine (n = 5), and L-spine (n = 5) with IRB consent. ASSESSMENT: Vendor-provided head, C-spine, T-spine, and L-spine protocols (SARRT ) were modified to meet both low SAR targets (SARLOW ) using the proposed workflow. in vitro SNR and CNR were evaluated with a T1 -T2 phantom. in vivo image quality and clinical acceptability were scored using a 5-point Likert scale for two blinded readers. FIELD STRENGTH/SEQUENCES: 1.5T/spin-echoes, gradient-echoes. STATISTICAL ANALYSIS: In vitro SNR and CNR values were evaluated with a repeated measures general linear model. in vivo image quality and clinical acceptability were evaluated using a generalized estimating equation analysis (GEE). The two reader's level of agreement was analyzed using Cohen's kappa statistical analysis. RESULTS: Using the workflow, SAR limits were met. LH-SAR: 0.12 ± 0.02 W/kg, median (SD) values for LH-SAR were 0.12 (0.02) W/kg and WB-SAR: 0.09 (0.01) W/kg. Examination time did not increase ≤2x the initial time. SARRT SNR values were higher and significantly different than SARLOW (P < 0.05). However, no significant difference was observed between the CNR values (value = 0.21). Median (IQR) CNR values were 14.2 (25.0) vs. 15.1 (9.2) for head, 12.1 (16.9) vs. 25.3 (14.2) for C-spine, 81.6 (70.1) vs. 71.0 (26.6) for T-spine, and 51.4 (52.6) vs. 37.7 (27.3) for L-spine. Image quality scores were not significantly different between SARRT and SARLOW (median [SD] scores were 4.0 [0.01] vs. 4.3 [0.2], P > 0.05). DATA CONCLUSION: The proposed workflow provides guidance for modifying routine MRI exams to achieve low SAR limits. This can benefit patients referred for an MRI exam with low SAR MR-conditional AIMDs. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2020;52:91-102.

Prostate diffusion MRI with minimal echo time using eddy current nulled convex optimized diffusion encoding.

BACKGROUND: Prostate diffusion-weighted imaging (DWI) using monopolar encoding is sensitive to eddy-current-induced distortion artifacts. Twice-refocused bipolar encoding suppresses eddy current artifacts, but increases echo time (TE), leading to lower signal-to-noise ratio (SNR). Optimization of the diffusion encoding might improve prostate DWI. PURPOSE: To evaluate eddy current nulled convex optimized diffusion encoding (ENCODE) for prostate DWI with minimal TE. STUDY TYPE: Prospective cohort study. POPULATION: A diffusion phantom, an ex vivo prostate specimen, 10 healthy male subjects (27 ± 3 years old), and five prostate cancer patients (62 ± 7 years old). FIELD STRENGTH/SEQUENCE: 3T; single-shot spin-echo echoplanar DWI. ASSESSMENT: Eddy-current artifacts, TE, SNR, apparent diffusion coefficient (ADC), and image quality scores from three independent readers were compared between monopolar, bipolar, and ENCODE prostate DWI for standard-resolution (1.6 × 1.6 mm2 , partial Fourier factor [pF] = 6/8) and higher-resolution protocols (1.6 × 1.6 mm2 , pF = off; 1.0 × 1.0 mm2 , pF = 6/8). STATISTICAL TESTING: SNR and ADC differences between techniques were tested with Kruskal-Wallis and Wilcoxon signed-rank tests (P < 0.05 considered significant). RESULTS: Eddy current suppression with ENCODE was comparable to bipolar encoding (mean coefficient of variation across three diffusion directions of 9.4% and 9%). For a standard-resolution protocol, ENCODE achieved similar TE as monopolar and reduced TE by 14 msec compared to bipolar, resulting in 27% and 29% higher mean SNR in prostate transition zone (TZ) and peripheral zone (PZ) (P < 0.05) compared to bipolar, respectively. For higher-resolution protocols, ENCODE achieved the shortest TE (67 msec), with 17-21% and 58-70% higher mean SNR compared to monopolar (TE = 77 msec) and bipolar (TE = 102 msec) in PZ and TZ (P < 0.05). No significant differences were found in mean TZ (P = 0.91) and PZ ADC (P = 0.94) between the three techniques. ENCODE achieved similar or higher image quality scores than bipolar DWI in patients, with mean intraclass correlation coefficient of 0.77 for overall quality between three independent readers. DATA CONCLUSION: ENCODE minimizes TE (improves SNR) and reduces eddy-current distortion for prostate DWI compared to monopolar and bipolar encoding. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2020;51:1526-1539.

Motion-Induced Signal Loss in In Vivo Cardiac Diffusion-Weighted Imaging.

LEVEL OF EVIDENCE: 5 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:319-320.