ChaMP-CMD: A Phenotype-Blinded, Randomized Controlled, Cross-Over Trial.

BACKGROUND: Angina with nonobstructive coronary arteries is a common condition for which no effective treatment has been established. We hypothesized that the measurement of coronary flow reserve (CFR) allows identification of patients with angina with nonobstructive coronary arteries who would benefit from anti-ischemic therapy. METHODS: Patients with angina with nonobstructive coronary arteries underwent blinded invasive CFR measurement and were randomly assigned to receive 4 weeks of amlodipine or ranolazine. After a 1-week washout, they crossed over to the other drug for 4 weeks; final assessment was after the cessation of study medication for another 4 weeks. The primary outcome was change in treadmill exercise time, and the secondary outcome was change in Seattle Angina Questionnaire summary score in response to anti-ischemic therapy. Analysis was on a per protocol basis according to the following classification: coronary microvascular disease (CMD group) if CFR<2.5 and reference group if CFR≥2.5. The study protocol was registered before the first patient was enrolled (International Standard Randomised Controlled Trial Number: ISRCTN94728379). RESULTS: Eighty-seven patients (61±8 years of age; 62% women) underwent random assignment (57 CMD group and 30 reference group). Baseline exercise time and Seattle Angina Questionnaire summary scores were similar between groups. The CMD group had a greater increment (delta) in exercise time than the reference group in response to both amlodipine (difference in delta, 82 s [95% CI, 37-126 s]; P<0.001) and ranolazine (difference in delta, 68 s [95% CI, 21-115 s]; P=0.005). The CMD group reported a greater increment (delta) in Seattle Angina Questionnaire summary score than the reference group in response to ranolazine (difference in delta, 7 points [95% CI, 0-15]; P=0.048), but not to amlodipine (difference in delta, 2 points [95% CI, -5 to 8]; P=0.549). CONCLUSIONS: Among phenotypically similar patients with angina with nonobstructive coronary arteries, only those with an impaired CFR derive benefit from anti-ischemic therapy. These findings support measurement of CFR to diagnose and guide management of this otherwise heterogeneous patient group.

Percutaneous Revascularization for Ischemic Left Ventricular Dysfunction.

BACKGROUND: Whether revascularization by percutaneous coronary intervention (PCI) can improve event-free survival and left ventricular function in patients with severe ischemic left ventricular systolic dysfunction, as compared with optimal medical therapy (i.e., individually adjusted pharmacologic and device therapy for heart failure) alone, is unknown. METHODS: We randomly assigned patients with a left ventricular ejection fraction of 35% or less, extensive coronary artery disease amenable to PCI, and demonstrable myocardial viability to a strategy of either PCI plus optimal medical therapy (PCI group) or optimal medical therapy alone (optimal-medical-therapy group). The primary composite outcome was death from any cause or hospitalization for heart failure. Major secondary outcomes were left ventricular ejection fraction at 6 and 12 months and quality-of-life scores. RESULTS: A total of 700 patients underwent randomization - 347 were assigned to the PCI group and 353 to the optimal-medical-therapy group. Over a median of 41 months, a primary-outcome event occurred in 129 patients (37.2%) in the PCI group and in 134 patients (38.0%) in the optimal-medical-therapy group (hazard ratio, 0.99; 95% confidence interval [CI], 0.78 to 1.27; P = 0.96). The left ventricular ejection fraction was similar in the two groups at 6 months (mean difference, -1.6 percentage points; 95% CI, -3.7 to 0.5) and at 12 months (mean difference, 0.9 percentage points; 95% CI, -1.7 to 3.4). Quality-of-life scores at 6 and 12 months appeared to favor the PCI group, but the difference had diminished at 24 months. CONCLUSIONS: Among patients with severe ischemic left ventricular systolic dysfunction who received optimal medical therapy, revascularization by PCI did not result in a lower incidence of death from any cause or hospitalization for heart failure. (Funded by the National Institute for Health and Care Research Health Technology Assessment Program; REVIVED-BCIS2 ClinicalTrials.gov number, NCT01920048.).

Myocardial Involvement After Hospitalization for COVID-19 Complicated by Troponin Elevation: A Prospective, Multicenter, Observational Study.

BACKGROUND: Acute myocardial injury in hospitalized patients with coronavirus disease 2019 (COVID-19) has a poor prognosis. Its associations and pathogenesis are unclear. Our aim was to assess the presence, nature, and extent of myocardial damage in hospitalized patients with troponin elevation. METHODS: Across 25 hospitals in the United Kingdom, 342 patients with COVID-19 and an elevated troponin level (COVID+/troponin+) were enrolled between June 2020 and March 2021 and had a magnetic resonance imaging scan within 28 days of discharge. Two prospective control groups were recruited, comprising 64 patients with COVID-19 and normal troponin levels (COVID+/troponin-) and 113 patients without COVID-19 or elevated troponin level matched by age and cardiovascular comorbidities (COVID-/comorbidity+). Regression modeling was performed to identify predictors of major adverse cardiovascular events at 12 months. RESULTS: Of the 519 included patients, 356 (69%) were men, with a median (interquartile range) age of 61.0 years (53.8, 68.8). The frequency of any heart abnormality, defined as left or right ventricular impairment, scar, or pericardial disease, was 2-fold greater in cases (61% [207/342]) compared with controls (36% [COVID+/troponin-] versus 31% [COVID-/comorbidity+]; P<0.001 for both). More cases than controls had ventricular impairment (17.2% versus 3.1% and 7.1%) or scar (42% versus 7% and 23%; P<0.001 for both). The myocardial injury pattern was different, with cases more likely than controls to have infarction (13% versus 2% and 7%; P<0.01) or microinfarction (9% versus 0% and 1%; P<0.001), but there was no difference in nonischemic scar (13% versus 5% and 14%; P=0.10). Using the Lake Louise magnetic resonance imaging criteria, the prevalence of probable recent myocarditis was 6.7% (23/342) in cases compared with 1.7% (2/113) in controls without COVID-19 (P=0.045). During follow-up, 4 patients died and 34 experienced a subsequent major adverse cardiovascular event (10.2%), which was similar to controls (6.1%; P=0.70). Myocardial scar, but not previous COVID-19 infection or troponin, was an independent predictor of major adverse cardiovascular events (odds ratio, 2.25 [95% CI, 1.12-4.57]; P=0.02). CONCLUSIONS: Compared with contemporary controls, patients with COVID-19 and elevated cardiac troponin level have more ventricular impairment and myocardial scar in early convalescence. However, the proportion with myocarditis was low and scar pathogenesis was diverse, including a newly described pattern of microinfarction. REGISTRATION: URL: https://www.isrctn.com; Unique identifier: 58667920.

Fast cardiac T1ρ,adiab mapping using slice-selective adiabatic spin-lock preparation pulses.

PURPOSE: Myocardial T1ρ mapping techniques commonly acquire multiple images in one breathhold to calculate a single-slice T1ρ map. Recently, non-selective adiabatic pulses have been used for robust spin-lock preparation (T1ρ,adiab). The objective of this study was to develop a fast multi-slice myocardial T1ρ,adiab mapping approach. METHODS: The proposed-sequence reduces the number of breathholds required for whole-heart 2D T1ρ,adiab mapping by acquiring multiple interleaved slices in each breathhold using slice-selective T1ρ,adiab preparation pulses. The proposed-sequence was implemented with two interleaved slices per breathhold scan and was quantitatively evaluated in phantom experiments and 10 healthy-volunteers against a single-slice T1ρ,adiab mapping sequence. The sequence was demonstrated in two patients with myocardial scar. RESULTS: The phantom experiments showed the proposed-sequence had slice-to-slice variation of 1.62% ± 1.05% and precision of 4.51 ± 0.68 ms. The healthy volunteer cohort subject-wise mean relaxation time was lower for the proposed-sequence than the single-slice sequence (137.7 ± 5.3 ms vs. 148.4 ± 8.3 ms, p < 0.001), and spatial-standard-deviation was better (18.7 ± 1.8 ms vs. 21.8 ± 3.4 ms, p < 0.018). The mean within-subject, coefficient of variation was 5.93% ± 1.57% for the proposed-sequence and 6.31% ± 1.92% for the single-slice sequence (p = 0.35) and the effect of slice variation (0.81 ± 4.87 ms) was not significantly different to zero (p = 0.61). In both patient examples increased T1ρ,adiab (maximum American Heart Association-segment mean = 174 and 197 ms) was measured within the myocardial scar. CONCLUSION: The proposed sequence provides a twofold acceleration for myocardial T1ρ,adiab mapping using a multi-slice approach. It has no significant difference in within-subject variability, and significantly better precision, compared to a 2D T1ρ,adiab mapping sequence based on non-selective adiabatic spin-lock preparations.

Automated inversion time selection for late gadolinium-enhanced cardiac magnetic resonance imaging.

OBJECTIVES: To develop and share a deep learning method that can accurately identify optimal inversion time (TI) from multi-vendor, multi-institutional and multi-field strength inversion scout (TI scout) sequences for late gadolinium enhancement cardiac MRI. MATERIALS AND METHODS: Retrospective multicentre study conducted on 1136 1.5-T and 3-T cardiac MRI examinations from four centres and three scanner vendors. Deep learning models, comprising a convolutional neural network (CNN) that provides input to a long short-term memory (LSTM) network, were trained on TI scout pixel data from centres 1 to 3 to identify optimal TI, using ground truth annotations by two readers. Accuracy within 50 ms, mean absolute error (MAE), Lin's concordance coefficient (LCCC) and reduced major axis regression (RMAR) were used to select the best model from validation results, and applied to holdout test data. Robustness of the best-performing model was also tested on imaging data from centre 4. RESULTS: The best model (SE-ResNet18-LSTM) produced accuracy of 96.1%, MAE 22.9 ms and LCCC 0.47 compared to ground truth on the holdout test set and accuracy of 97.3%, MAE 15.2 ms and LCCC 0.64 when tested on unseen external (centre 4) data. Differences in vendor performance were observed, with greatest accuracy for the most commonly represented vendor in the training data. CONCLUSION: A deep learning model was developed that can identify optimal inversion time from TI scout images on multi-vendor data with high accuracy, including on previously unseen external data. We make this model available to the scientific community for further assessment or development. CLINICAL RELEVANCE STATEMENT: A robust automated inversion time selection tool for late gadolinium-enhanced imaging allows for reproducible and efficient cross-vendor inversion time selection. KEY POINTS: • A model comprising convolutional and recurrent neural networks was developed to extract optimal TI from TI scout images. • Model accuracy within 50 ms of ground truth on multi-vendor holdout and external data of 96.1% and 97.3% respectively was achieved. • This model could improve workflow efficiency and standardise optimal TI selection for consistent LGE imaging.

Myocardial Fibrosis at Cardiac MRI Helps Predict Adverse Clinical Outcome in Patients with Mitral Valve Prolapse.

Background Patients with mitral valve prolapse (MVP) may develop adverse outcomes even in the absence of mitral regurgitation or left ventricular (LV) dysfunction. Purpose To investigate the prognostic value of mitral annulus disjunction (MAD) and myocardial fibrosis at late gadolinium enhancement (LGE) cardiac MRI in patients with MVP without moderate-to-severe mitral regurgitation or LV dysfunction. Materials and Methods In this longitudinal retrospective study, 118 144 cardiac MRI studies were evaluated between October 2007 and June 2020 at 15 European tertiary medical centers. Follow-up was from the date of cardiac MRI examination to June 2020; the minimum and maximum follow-up intervals were 6 months and 156 months, respectively. Patients were excluded if at least one of the following conditions was present: cardiomyopathy, LV ejection fraction less than 40%, ischemic heart disease, congenital heart disease, inflammatory heart disease, moderate or worse mitral regurgitation, participation in competitive sport, or electrocardiogram suggestive of channelopathies. In the remainder, cardiac MRI studies were reanalyzed, and patients were included if they were aged 18 years or older, MVP was diagnosed at cardiac MRI, and clinical information and electrocardiogram monitoring were available within 3 months from cardiac MRI examination. The end point was a composite of adverse outcomes: sustained ventricular tachycardia (VT), sudden cardiac death (SCD), or unexplained syncope. Multivariable Cox regression analysis was performed. Results A total of 474 patients (mean age, 47 years ± 16 [SD]; 244 women) were included. Over a median follow-up of 3.3 years, 18 patients (4%) reached the study end point. LGE presence (hazard ratio, 4.2 [95% CI: 1.5, 11.9]; P = .006) and extent (hazard ratio, 1.2 per 1% increase [95% CI: 1.1, 1.4]; P = .006), but not MAD presence (P = .89), were associated with clinical outcome. LGE presence had incremental prognostic value over MVP severity and sustained VT and aborted SCD at baseline (area under the receiver operating characteristic curve, 0.70 vs 0.62; P = .03). Conclusion In contrast to mitral annulus disjunction, myocardial fibrosis determined according to late gadolinium enhancement at cardiac MRI was associated with adverse outcome in patients with mitral valve prolapse without moderate-to-severe mitral regurgitation or left ventricular dysfunction. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Gerber in this issue.

Effect of active vitamin-D on left ventricular mass index: Results of a randomized controlled trial in type 2 diabetes and chronic kidney disease.

BACKGROUND: Active vitamin-D deficiency is a potential modifiable risk factor for increased ventricular mass. We explored the effects of active vitamin-D (calcitriol) treatment on left ventricular mass in patients with type-2 diabetes (T2D) and chronic kidney disease (CKD). METHODS: We performed a 48-week duration single center randomized double-blind parallel group trial examining the impact of calcitriol, 0.5 mcg once daily, as compared to placebo on a primary endpoint of change from baseline in left ventricular mass index (LVMI) measured by magnetic resonance imaging . Patients with T2D, CKD stage-3 and raised left ventricular mass on stable renin angiotensin aldosterone system blockade, who all had elevated intact parathyroid hormone were eligible. Secondary endpoints included interstitial myocardial fibrosis, assessed with cardiac magnetic resonance imaging. In total, 45 (male 73%) patients with T2D and stage-3 CKD were studied (calcitriol n = 19, placebo n = 26). RESULTS: Following 48-weeks calcitriol treatment, the median difference and the (95% CI) of LVMI between the 2 treatment arms was 1.84 (-1.28, 4.96), similar between the 2 groups studied. Intact parathyroid hormone fell only in the calcitriol group from 142 pg/mL (80-293) to 76 pg/mL (41-204)(median, interquartile range, P= .04). No significant differences were observed in interstitial myocardial fibrosis or other secondary endpoints. CONCLUSIONS: The study did not provide evidence that treatment with calcitriol as compared to placebo might improve LVMI in patients with T2D, mild left ventricular hypertrophy and stable CKD. Our data does not support the routine use of active vitamin-D for LVMI regression and cardiovascular protection in patients with T2D and stage-3 CKD.

Low-rank motion correction for accelerated free-breathing first-pass myocardial perfusion imaging.

PURPOSE: Develop a novel approach for accelerated 2D free-breathing myocardial perfusion via low-rank motion-corrected (LRMC) reconstructions. METHODS: Myocardial perfusion imaging requires high spatial and temporal resolution, despite scan time constraints. Here, we incorporate LRMC models into the reconstruction-encoding operator, together with high-dimensionality patch-based regularization, to produce high quality, motion-corrected myocardial perfusion series from free-breathing acquisitions. The proposed framework estimates beat-to-beat nonrigid respiratory (and any other incidental) motion and the dynamic contrast subspace from the actual acquired data, which are then incorporated into the proposed LRMC reconstruction. LRMC was compared with iterative SENSitivity Encoding (SENSE) (itSENSE) and low-rank plus sparse (LpS) reconstruction in 10 patients based on image-quality scoring and ranking by two clinical expert readers. RESULTS: LRMC achieved significantly improved results relative to itSENSE and LpS in terms of image sharpness, temporal coefficient of variation, and expert reader evaluation. Left ventricle image sharpness was approximately 75%, 79%, and 86% for itSENSE, LpS and LRMC, respectively, indicating improved image sharpness for the proposed approach. Corresponding temporal coefficient of variation results were 23%, 11% and 7%, demonstrating improved temporal fidelity of the perfusion signal with the proposed LRMC. Corresponding clinical expert reader scores (1-5, from poor to excellent image quality) were 3.3, 3.9 and 4.9, demonstrating improved image quality with the proposed LRMC, in agreement with the automated metrics. CONCLUSION: LRMC produces motion-corrected myocardial perfusion in free-breathing acquisitions with substantially improved image quality when compared with iterative SENSE and LpS reconstructions.

Myocardial viability testing: all STICHed up, or about to be REVIVED?

Patients with ischaemic left ventricular dysfunction frequently undergo myocardial viability testing. The historical model presumes that those who have extensive areas of dysfunctional-yet-viable myocardium derive particular benefit from revascularization, whilst those without extensive viability do not. These suppositions rely on the theory of hibernation and are based on data of low quality: taking a dogmatic approach may therefore lead to patients being refused appropriate, prognostically important treatment. Recent data from a sub-study of the randomized STICH trial challenges these historical concepts, as the volume of viable myocardium failed to predict the effectiveness of coronary artery bypass grafting. Should the Heart Team now abandon viability testing, or are new paradigms needed in the way we interpret viability? This state-of-the-art review critically examines the evidence base for viability testing, focusing in particular on the presumed interactions between viability, functional recovery, revascularization and prognosis which underly the traditional model. We consider whether viability should relate solely to dysfunctional myocardium or be considered more broadly and explore wider uses of viability testingoutside of revascularization decision-making. Finally, we look forward to ongoing and future randomized trials, which will shape evidence-based clinical practice in the future.

Quantification of balanced SSFP myocardial perfusion imaging at 1.5 T: Impact of the reference image.

PURPOSE: To investigate the use of a high flip-angle (HFA) balanced SSFP (bSSFP) reference image (in comparison to conventional proton density [PD]-weighted reference images) for conversion of bSSFP myocardial perfusion images into dynamic T1 maps for improved myocardial blood flow (MBF) quantification at 1.5 T. METHODS: The HFA-bSSFP (flip angle [FA] = 50°), PD gradient-echo (PD-GRE; FA = 5°), and PD-bSSFP (FA = 8°) reference images were acquired before a dual-sequence bSSFP perfusion acquisition. Simulations were used to study accuracy and precision of T1 and MBF quantification using the three techniques. The accuracy and precision of T1 , and the precision and intersegment variability of MBF were compared among the three techniques in 8 patients under rest conditions. RESULTS: In simulations, HFA-bSSFP demonstrated improved T1 /MBF precision (higher T1 /MBF SD of 30%-80%/50%-100% and 30%-90%/60%-115% for PD-GRE and PD-bSSFP, respectively). Proton density-GRE and PD-bSSFP were more sensitive to effective FA than HFA-bSSFP (maximum T1 /MBF errors of 13%/43%, 20%/43%, and 1%/3%, respectively). Sensitivity of all techniques (defined as T1 /MBF errors) to native T1 , native T2 , and effective saturation efficiency were negligible (<1%/<1%), moderate (<14%/<19%), and high (<63%/<94%), respectively. In vivo, no difference in T1 accuracy was observed among HFA-bSSFP, PD-GRE, and PD-bSSFP (-9 ± 44 ms vs -28 ± 55 ms vs -22 ± 71 ms, respectively; p > .08). The HFA-bSSFP led to improved T1 /MBF precision (T1 /MBF SD: 41 ± 19 ms/0.24 ± 0.08 mL/g/min vs PD-GRE: 48 ± 20 ms/0.29 ± 0.09 mL/g/min and PD-bSSFP: 59 ± 23 ms/0.33 ± 0.11 mL/g/min; p ≤ .02) and lower MBF intersegment variability (0.14 ± 0.09 mL/g/min vs PD-GRE: 0.21 ± 0.09 mL/g/min and PD-bSSFP: 0.20 ± 0.10 mL/g/min; p ≤ .046). CONCLUSION: We have demonstrated the feasibility of using a HFA-bSSFP reference image for MBF quantification of bSSFP perfusion imaging at 1.5 T. Results from simulations demonstrate that the HFA-bSSFP reference image results in improved precision and reduced sensitivity to effective FA compared with conventional techniques using a PD reference image. Preliminary in vivo data acquired at rest also demonstrate improved precision and intersegment variability using the HFA-bSSFP technique compared with PD techniques; however, a clinical study in patients with coronary artery disease under stress conditions is required to determine the clinical significance of this finding.

Simultaneous multislice steady-state free precession myocardial perfusion with full left ventricular coverage and high resolution at 1.5 T.

PURPOSE: To implement and evaluate a simultaneous multi-slice balanced SSFP (SMS-bSSFP) perfusion sequence and compressed sensing reconstruction for cardiac MR perfusion imaging with full left ventricular (LV) coverage (nine slices/heartbeat) and high spatial resolution (1.4 × 1.4 mm2 ) at 1.5T. METHODS: A preliminary study was performed to evaluate the performance of blipped controlled aliasing in parallel imaging (CAIPI) and RF-CAIPI with gradient-controlled local Larmor adjustment (GC-LOLA) in the presence of fat. A nine-slice SMS-bSSFP sequence using RF-CAIPI with GC-LOLA with high spatial resolution (1.4 × 1.4 mm2 ) and a conventional three-slice sequence with conventional spatial resolution (1.9 × 1.9 mm2 ) were then acquired in 10 patients under rest conditions. Qualitative assessment was performed to assess image quality and perceived signal-to-noise ratio (SNR) on a 4-point scale (0: poor image quality/low SNR; 3: excellent image quality/high SNR), and the number of myocardial segments with diagnostic image quality was recorded. Quantitative measurements of myocardial sharpness and upslope index were performed. RESULTS: Fat signal leakage was significantly higher for blipped CAIPI than for RF-CAIPI with GC-LOLA (7.9% vs. 1.2%, p = 0.010). All 10 SMS-bSSFP perfusion datasets resulted in 16/16 diagnostic myocardial segments. There were no significant differences between the SMS and conventional acquisitions in terms of image quality (2.6 ± 0.6 vs. 2.7 ± 0.2, p = 0.8) or perceived SNR (2.8 ± 0.3 vs. 2.7 ± 0.3, p = 0.3). Inter-reader variability was good for both image quality (ICC = 0.84) and perceived SNR (ICC = 0.70). Myocardial sharpness was improved using the SMS sequence compared to the conventional sequence (0.37 ± 0.08 vs 0.32 ± 0.05, p < 0.001). There was no significant difference between measurements of upslope index for the SMS and conventional sequences (0.11 ± 0.04 vs. 0.11 ± 0.03, p = 0.84). CONCLUSION: SMS-bSSFP with multiband factor 3 and compressed sensing reconstruction enables cardiac MR perfusion imaging with three-fold increased spatial coverage and improved myocardial sharpness compared to a conventional sequence, without compromising perceived SNR, image quality, upslope index or number of diagnostic segments.

Impact of Temporal Resolution and Methods for Correction on Cardiac Magnetic Resonance Perfusion Quantification.

BACKGROUND: Acquisition of magnetic resonance first-pass perfusion images is synchronized to the patient's heart rate (HR) and governs the temporal resolution. This is inherently linked to the process of myocardial blood flow (MBF) quantification and impacts MBF accuracy but to an unclear extent. PURPOSE: To assess the impact of temporal resolution on quantitative perfusion and compare approaches for accounting for its variability. STUDY TYPE: Prospective phantom and retrospective clinical study. POPULATION AND PHANTOM: Simulations, a cardiac perfusion phantom, and 30 patients with (16, 53%) or without (14, 47%) coronary artery disease. FIELD STRENGTH/SEQUENCE: 3.0 T/2D saturation recovery spoiled gradient echo sequence. ASSESSMENT: Dynamic perfusion data were simulated for a range of reference MBF (1 mL/g/min-5 mL/g/min) and HR (30 bpm-150 bpm). Perfusion imaging was performed in patients and a phantom for different temporal resolutions. MBF and myocardial perfusion reserve (MPR) were quantified without correction for temporal resolution or following correction by either MBF scaling based on the sampling interval or data interpolation prior to quantification. Simulated data were quantified using Fermi deconvolution, truncated singular value decomposition, and one-compartment modeling, whereas phantom and clinical data were quantified using Fermi deconvolution alone. STATISTICAL TESTS: Shapiro-Wilk tests for normality, percentage error (PE) for measuring MBF accuracy in simulations, and one-way repeated measures analysis of variance with Bonferroni correction to compare clinical MBF and MPR. Statistical significance set at P < 0.05. RESULTS: For Fermi deconvolution and an example simulated 1 mL/g/min, the MBF PE without correction for temporal resolution was between 55.4% and -62.7% across 30-150 bpm. PE was between -22.2% and -6.8% following MBF scaling and between -14.2% and -14.2% following data interpolation across the same HR. An interpolated HR of 240 bpm reduced PE to ≤10%. Clinical rest and stress MBF and MPR were significantly different between analyses. DATA CONCLUSION: Accurate perfusion quantification needs to account for the variability of temporal resolution, with data interpolation prior to quantification reducing MBF variability across different resolutions. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 1.

Histopathological Validation of Dark-Blood Late Gadolinium Enhancement MRI Without Additional Magnetization Preparation.

BACKGROUND: Conventional bright-blood late gadolinium enhancement (LGE) cardiac magnetic resonance imaging (MRI) often suffers from poor scar-to-blood contrast due to the bright blood pool adjacent to the enhanced scar tissue. Recently, a dark-blood LGE method was developed which increases scar-to-blood contrast without using additional magnetization preparation. PURPOSE: We aim to histopathologically validate this dark-blood LGE method in a porcine animal model with induced myocardial infarction (MI). STUDY TYPE: Prospective. ANIMAL MODEL: Thirteen female Yorkshire pigs. FIELD STRENGTH/SEQUENCE: 1.5 T, two-dimensional phase-sensitive inversion-recovery radiofrequency-spoiled turbo field-echo. ASSESSMENT: MI was experimentally induced by transient coronary artery occlusion. At 1-week and 7-week post-infarction, in-vivo cardiac MRI was performed including conventional bright-blood and novel dark-blood LGE. Following the second MRI examination, the animals were sacrificed, and histopathology was obtained. Matching LGE slices and histopathology samples were selected based on anatomical landmarks. Independent observers, while blinded to other data, manually delineated the endocardial, epicardial, and infarct borders on either LGE images or histopathology samples. The percentage of infarcted left-ventricular myocardium was calculated for both LGE methods on a per-slice basis, and compared with histopathology as reference standard. Contrast-to-noise ratios were calculated for both LGE methods at 1-week and 7-week post-infarction. STATISTICAL TESTS: Pearson's correlation coefficient and paired-sample t-tests were used. Significance was set at P < 0.05. RESULTS: A combined total of 24 matched LGE and histopathology slices were available for histopathological validation. Dark-blood LGE demonstrated a high level of agreement compared to histopathology with no significant bias (-0.03%, P = 0.75). In contrast, bright-blood LGE showed a significant bias of -1.57% (P = 0.03) with larger 95% limits of agreement than dark-blood LGE. Image analysis demonstrated significantly higher scar-to-blood contrast for dark-blood LGE compared to bright-blood LGE, at both 1-week and 7-weeks post-infarction. DATA CONCLUSION: Dark-blood LGE without additional magnetization preparation provides superior visualization and quantification of ischemic scar compared to the current in vivo reference standard. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.

CardiSort: a convolutional neural network for cross vendor automated sorting of cardiac MR images.

OBJECTIVES: To develop an image-based automatic deep learning method to classify cardiac MR images by sequence type and imaging plane for improved clinical post-processing efficiency. METHODS: Multivendor cardiac MRI studies were retrospectively collected from 4 centres and 3 vendors. A two-head convolutional neural network ('CardiSort') was trained to classify 35 sequences by imaging sequence (n = 17) and plane (n = 10). Single vendor training (SVT) on single-centre images (n = 234 patients) and multivendor training (MVT) with multicentre images (n = 434 patients, 3 centres) were performed. Model accuracy and F1 scores on a hold-out test set were calculated, with ground truth labels by an expert radiologist. External validation of MVT (MVTexternal) was performed on data from 3 previously unseen magnet systems from 2 vendors (n = 80 patients). RESULTS: Model sequence/plane/overall accuracy and F1-scores were 85.2%/93.2%/81.8% and 0.82 for SVT and 96.1%/97.9%/94.3% and 0.94 MVT on the hold-out test set. MVTexternal yielded sequence/plane/combined accuracy and F1-scores of 92.7%/93.0%/86.6% and 0.86. There was high accuracy for common sequences and conventional cardiac planes. Poor accuracy was observed for underrepresented classes and sequences where there was greater variability in acquisition parameters across centres, such as perfusion imaging. CONCLUSIONS: A deep learning network was developed on multivendor data to classify MRI studies into component sequences and planes, with external validation. With refinement, it has potential to improve workflow by enabling automated sequence selection, an important first step in completely automated post-processing pipelines. KEY POINTS: • Deep learning can be applied for consistent and efficient classification of cardiac MR image types. • A multicentre, multivendor study using a deep learning algorithm (CardiSort) showed high classification accuracy on a hold-out test set with good generalisation to images from previously unseen magnet systems. • CardiSort has potential to improve clinical workflows, as a vital first step in developing fully automated post-processing pipelines.

High-resolution non-contrast free-breathing coronary cardiovascular magnetic resonance angiography for detection of coronary artery disease: validation against invasive coronary angiography.

BACKGROUND: Coronary artery disease (CAD) is the single most common cause of death worldwide. Recent technological developments with coronary cardiovascular magnetic resonance angiography (CCMRA) allow high-resolution free-breathing imaging of the coronary arteries at submillimeter resolution without contrast in a predictable scan time of ~ 10 min. The objective of this study was to determine the diagnostic accuracy of high-resolution CCMRA for CAD detection against the gold standard of invasive coronary angiography (ICA). METHODS: Forty-five patients (15 female, 62 ± 10 years) with suspected CAD underwent sub-millimeter-resolution (0.6 mm3) non-contrast CCMRA at 1.5T in this prospective clinical study from 2019-2020. Prior to CCMR, patients were given an intravenous beta blockers to optimize heart rate control and sublingual glyceryl trinitrate to promote coronary vasodilation. Obstructive CAD was defined by lesions with ≥ 50% stenosis by quantitative coronary angiography on ICA. RESULTS: The mean duration of image acquisition was 10.4 ± 2.1 min. On a per patient analysis, the sensitivity, specificity, positive predictive value and negative predictive value (95% confidence intervals) were 95% (75-100), 54% (36-71), 60% (42-75) and 93% (70-100), respectively. On a per vessel analysis the sensitivity, specificity, positive predictive value and negative predictive value (95% confidence intervals) were 80% (63-91), 83% (77-88), 49% (36-63) and 95% (90-98), respectively. CONCLUSION: As an important step towards clinical translation, we demonstrated a good diagnostic accuracy for CAD detection using high-resolution CCMRA, with high sensitivity and negative predictive value. The positive predictive value is moderate, and combination with CMR stress perfusion may improve the diagnostic accuracy. Future multicenter evaluation is now required.

A fast navigator (fastNAV) for prospective respiratory motion correction in first-pass myocardial perfusion imaging.

PURPOSE: To develop and evaluate a fast respiratory navigator (fastNAV) for cardiac MR perfusion imaging with subject-specific prospective slice tracking. METHODS: A fastNAV was developed for dynamic contrast-enhanced cardiac MR perfusion imaging by combining spatially nonselective saturation with slice-selective tip-up and slice-selective excitation pulses. The excitation slice was angulated from the tip-up slice in the transverse plane to overlap only in the right hemidiaphragm for suppression of signal outside the right hemidiaphragm. A calibration scan was developed to enable the estimation of subject-specific tracking factors. Perfusion imaging using subject-specific fastNAV-based slice tracking was then compared to a conventional sequence (ie, without slice tracking) in 10 patients under free-breathing conditions. Respiratory motion in perfusion images was quantitatively assessed by measuring the average overlap of the left ventricle across images (avDice, 0:no overlap/1:perfect overlap) and the average displacement of the center of mass of the left ventricle (avCoM). Image quality was subjectively assessed using a 4-point scoring system (1: poor, 4: excellent). RESULTS: The fastNAV calibration was successfully performed in all subjects (average tracking factor of 0.46 ± 0.13, R = 0.94 ± 0.03). Prospective motion correction using fastNAV led to higher avDice (0.94 ± 0.02 vs. 0.90 ± 0.03, P < .001) and reduced avCoM (4.03 ± 0.84 vs. 5.22 ± 1.22, P < .001). There were no statistically significant differences between the 2 sequences in terms of image quality (both sequences: median = 3 and interquartile range = 3-4, P = 1). CONCLUSION: fastNAV enables fast and robust right hemidiaphragm motion tracking in a perfusion sequence. In combination with subject-specific slice tracking, fastNAV reduces the effect of respiratory motion during free-breathing cardiac MR perfusion imaging.

All-systolic first-pass myocardial rest perfusion at a long saturation time using simultaneous multi-slice imaging and compressed sensing acceleration.

PURPOSE: To enable all-systolic first-pass rest myocardial perfusion with long saturation times. To investigate the change in perfusion contrast and dark rim artefacts through simulations and surrogate measurements. METHODS: Simulations were employed to investigate optimal saturation time for myocardium-perfusion defect contrast and blood-to-myocardium signal ratios. Two saturation recovery blocks with long/short saturation times (LTS/STS) were employed to image 3 slices at end-systole and diastole. Simultaneous multi-slice balanced steady state free precession imaging and compressed sensing acceleration were combined. The sequence was compared to a 3 slice-by-slice clinical protocol in 10 patients. Quantitative assessment of myocardium-peak pre contrast and blood-to-myocardium signal ratios, as well as qualitative assessment of perceived SNR, image quality, blurring, and dark rim artefacts, were performed. RESULTS: Simulations showed that with a bolus of 0.075 mmol/kg, a LTS of 240-470 ms led to a relative increase in myocardium-perfusion defect contrast of 34% ± 9%-28% ± 27% than a STS = 120 ms, while reducing blood-to-myocardium signal ratio by 18% ± 10%-32% ± 14% at peak myocardium. With a bolus of 0.05 mmol/kg, LTS was 320-570 ms with an increase in myocardium-perfusion defect contrast of 63% ± 13%-62% ± 29%. Across patients, LTS led to an average increase in myocardium-peak pre contrast of 59% (P < .001) at peak myocardium and a lower blood-to-myocardium signal ratio of 47% (P < .001) and 15% (P < .001) at peak blood/myocardium. LTS had improved motion robustness (P = .002), image quality (P < .001), and decreased dark rim artefacts (P = .008) than the clinical protocol. CONCLUSION: All-systolic rest perfusion can be achieved by combining simultaneous multi-slice and compressed sensing acceleration, enabling 3-slice cardiac coverage with reduced motion and dark rim artefacts. Numerical simulations indicate that myocardium-perfusion defect contrast increases at LTS.

Influence of the arterial input sampling location on the diagnostic accuracy of cardiovascular magnetic resonance stress myocardial perfusion quantification.

BACKGROUND: Quantification of myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) by cardiovascular magnetic resonance (CMR) perfusion requires sampling of the arterial input function (AIF). While variation in the AIF sampling location is known to impact quantification by CMR and positron emission tomography (PET) perfusion, there is no evidence to support the use of a specific location based on their diagnostic accuracy in the detection of coronary artery disease (CAD). This study aimed to evaluate the accuracy of stress MBF and MPR for different AIF sampling locations for the detection of abnormal myocardial perfusion with expert visual assessment as the reference. METHODS: Twenty-five patients with suspected or known CAD underwent vasodilator stress-rest perfusion with a dual-sequence technique at 3T. A low-resolution slice was acquired in 3-chamber view to allow AIF sampling at five different locations: left atrium (LA), basal left ventricle (bLV), mid left ventricle (mLV), apical left ventricle (aLV) and aortic root (AoR). MBF and MPR were estimated at the segmental level using Fermi function-constrained deconvolution. Segments were scored as having normal or abnormal perfusion by visual assessment and the diagnostic accuracy of stress MBF and MPR for each location was evaluated using receiver operating characteristic curve analysis. RESULTS: In both normal (300 out of 400, 75 %) and abnormal segments, rest MBF, stress MBF and MPR were significantly different across AIF sampling locations (p < 0.001). Stress MBF for the AoR (normal: 2.42 (2.15-2.84) mL/g/min; abnormal: 1.71 (1.28-1.98) mL/g/min) had the highest diagnostic accuracy (sensitivity 80 %, specificity 85 %, area under the curve 0.90; p < 0.001 versus stress MBF for all other locations including bLV: normal: 2.78 (2.39-3.14) mL/g/min; abnormal: 2.22 (1.83-2.48) mL/g/min; sensitivity 91 %, specificity 63 %, area under the curve 0.81) and performed better than MPR for the LV locations (p < 0.01). MPR for the AoR (normal: 2.43 (1.95-3.14); abnormal: 1.58 (1.34-1.90)) was not superior to MPR for the bLV (normal: 2.59 (2.04-3.20); abnormal: 1.69 (1.36-2.14); p = 0.717). CONCLUSIONS: The AIF sampling location has a significant impact on MBF and MPR estimates by CMR perfusion, with AoR-based stress MBF comparing favorably to that for the current clinical reference bLV.

Dark-blood late gadolinium enhancement cardiovascular magnetic resonance for improved detection of subendocardial scar: a review of current techniques.

For almost 20 years, late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) has been the reference standard for the non-invasive assessment of myocardial viability. Since the blood pool often appears equally bright as the enhanced scar regions, detection of subendocardial scar patterns can be challenging. Various novel LGE methods have been proposed that null or suppress the blood signal by employing additional magnetization preparation mechanisms. This review aims to provide a comprehensive overview of these dark-blood LGE methods, discussing the magnetization preparation schemes and findings in phantom, preclinical, and clinical studies. Finally, conclusions on the current evidence and limitations are drawn and new avenues for future research are discussed. Dark-blood LGE methods are a promising new tool for non-invasive assessment of myocardial viability. For a mainstream adoption of dark-blood LGE, however, clinical availability and ease of use are crucial.

First-phase ejection fraction by cardiovascular magnetic resonance predicts outcomes in aortic stenosis.

BACKGROUND: First-phase ejection fraction (EF1; the ejection fraction measured during active systole up to the time of maximal aortic flow) measured by transthoracic echocardiography (TTE) is a powerful predictor of outcomes in patients with aortic stenosis. We aimed to assess whether cardiovascular magnetic resonance (CMR) might provide more precise measurements of EF1 than TTE and to examine the correlation of CMR EF1 with measures of fibrosis. METHODS: In 141 patients with at least mild aortic stenosis, we measured CMR EF1 from a short-axis 3D stack and compared its variability with TTE EF1, and its associations with myocardial fibrosis and clinical outcome (aortic valve replacement (AVR) or death). RESULTS: Intra- and inter-observer variation of CMR EF1 (standard deviations of differences within and between observers of 2.3% and 2.5% units respectively) was approximately 50% that of TTE EF1. CMR EF1 was strongly predictive of AVR or death. On multivariable Cox proportional hazards analysis, the hazard ratio for CMR EF1 was 0.93 (95% confidence interval 0.89-0.97, p = 0.001) per % change in EF1 and, apart from aortic valve gradient, CMR EF1 was the only imaging or biochemical measure independently predictive of outcome. Indexed extracellular volume was associated with AVR or death, but not after adjusting for EF1. CONCLUSIONS: EF1 is a simple robust marker of early left ventricular impairment that can be precisely measured by CMR and predicts outcome in aortic stenosis. Its measurement by CMR is more reproducible than that by TTE and may facilitate left ventricular structure-function analysis.