Effect of Cangrelor on Infarct Size in ST-Segment-Elevation Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention: A Randomized Controlled Trial (The PITRI Trial).

BACKGROUND: The administration of intravenous cangrelor at reperfusion achieves faster onset of platelet P2Y12 inhibition than oral ticagrelor and has been shown to reduce myocardial infarction (MI) size in the preclinical setting. We hypothesized that the administration of cangrelor at reperfusion will reduce MI size and prevent microvascular obstruction in patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention. METHODS: This was a phase 2, multicenter, randomized, double-blind, placebo-controlled clinical trial conducted between November 2017 to November 2021 in 6 cardiac centers in Singapore. Patients were randomized to receive either cangrelor or placebo initiated before the primary percutaneous coronary intervention procedure on top of oral ticagrelor. The key exclusion criteria included presenting <6 hours of symptom onset; previous MI and stroke or transient ischemic attack; on concomitant oral anticoagulants; and a contraindication for cardiovascular magnetic resonance. The primary efficacy end point was acute MI size by cardiovascular magnetic resonance within the first week expressed as percentage of the left ventricle mass (%LVmass). Microvascular obstruction was identified as areas of dark core of hypoenhancement within areas of late gadolinium enhancement. The primary safety end point was Bleeding Academic Research Consortium-defined major bleeding in the first 48 hours. Continuous variables were compared by Mann-Whitney U test (reported as median [first quartile-third quartile]), and categorical variables were compared by Fisher exact test. A 2-sided P<0.05 was considered statistically significant. RESULTS: Of 209 recruited patients, 164 patients (78%) completed the acute cardiovascular magnetic resonance scan. There were no significant differences in acute MI size (placebo, 14.9% [7.3-22.6] %LVmass versus cangrelor, 16.3 [9.9-24.4] %LVmass; P=0.40) or the incidence (placebo, 48% versus cangrelor, 47%; P=0.99) and extent of microvascular obstruction (placebo, 1.63 [0.60-4.65] %LVmass versus cangrelor, 1.18 [0.53-3.37] %LVmass; P=0.46) between placebo and cangrelor despite a 2-fold decrease in platelet reactivity with cangrelor. There were no Bleeding Academic Research Consortium-defined major bleeding events in either group in the first 48 hours. CONCLUSIONS: Cangrelor administered at the time of primary percutaneous coronary intervention did not reduce acute MI size or prevent microvascular obstruction in patients with ST-segment-elevation MI given oral ticagrelor despite a significant reduction of platelet reactivity during the percutaneous coronary intervention procedure. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03102723.

Evaluation of trigeminal nerve tractography using two-fold-accelerated simultaneous multi-slice readout-segmented echo planar diffusion tensor imaging.

OBJECTIVES: Simultaneous multi-slice (SMS) imaging with short repetition time (TR) accelerates diffusion tensor imaging (DTI) acquisitions. However, its impact when combined with readout-segmented echo planar imaging (RESOLVE) on the cranial nerves given the challenging skull base/posterior fossa terrain is unexplored. We evaluated the reliability of trigeminal nerve DTI metrics using SMS with RESOLVE-DTI. METHODS: Eight healthy controls and six patients with unilateral trigeminal neuralgia (TN) underwent brain MRI scan. Three different RESOLVE-DTI protocols were performed on a 3-T MRI system: non-SMS (TR = 4330 ms), SMS with identical TR (4330 ms), and SMS with short TR (2400 ms). Pontine signal-to-noise ratio (SNR) and DTI metrics of the trigeminal nerve streamlines tracked by two independent raters using deterministic tractography and standardized tracking protocol were obtained. These were statistically analyzed and compared across the three protocols using intra-rater and inter-rater intraclass correlation coefficients (ICCs), one-way analysis of variance (ANOVA), post hoc analysis, and linear regression. RESULTS: On visual screening, there were no artifacts across the trigeminal nerves. All data also cleared objective image quality assurance analysis. Pontine SNR was similar for the two SMS protocols and higher for the non-SMS RESOLVE-DTI (F(2,36) = 4.40, p = 0.02). Intra-rater and inter-rater ICCs were very good (> 0.85). Trigeminal nerve DTI metrics were consistently measured by the three protocols, revealing significant linear relationships between non-SMS- and SMS-derived DTI metrics. CONCLUSION: SMS RESOLVE-DTI enables fast and reliable evaluation of microstructural integrity of the trigeminal nerve, with potential application in the clinical management of TN. KEY POINTS: • Readout-segmented diffusion-weighted echo planar imaging (RESOLVE-DTI) reduces image distortion artifacts in the posterior fossa but its long acquisition time limits clinical utility. • Simultaneous multi-slice (SMS) imaging combined with RESOLVE-DTI provides reliable trigeminal nerve tractography with potential applications in trigeminal neuralgia. • Two-fold-accelerated RESOLVE-DTI yields comparable trigeminal nerve streamlines and DTI metrics while near-halving acquisition time.

Joint intracranial and carotid vessel wall imaging in 5 minutes using compressed sensing accelerated DANTE-SPACE.

OBJECTIVES: To compare visualization of joint intracranial and carotid vessel walls between 5× compressed sensing accelerated three-dimensional DANTE-SPACE sequence (CS VWI) acquired in 5 min and the same sequence accelerated by 2.7× parallel imaging (PI VWI) which takes 9-10 min currently. METHODS: Following institutional review board approval and informed consent, 28 subjects including 20 stroke patients underwent PI and CS VWI examinations with an acquired spatial resolution of isotropic 0.55 mm and joint coverage of intracranial and carotid arteries. Quantitative wall thickness measurements of CS VWI and PI VWI were compared on healthy volunteers and patients with wall thickening respectively. Subjective wall visualizations of the two VWI methods on patients were scored by two radiologists blindly and independently using a 4-point scale followed by inter-rater reproducibility analysis. RESULTS: Linear regression analysis of wall thickness measurements showed excellent agreement between CS VWI and PI VWI in both healthy volunteers (r = 0.99) and stroke patients with wall thickening (r = 0.99). Subjective wall visualization score of CS VWI was slightly lower than PI VWI (3.13 ± 0.41 vs. 3.31 ± 0.79) but still had good diagnostic quality (> 3 based on a 4-point scale). The two radiologists' scores agreed excellently, evidenced by the intraclass correlation coefficient (ICC) values being higher than 0.75 (p < 0.001). CONCLUSIONS: Compressed sensing expedients joint intracranial and carotid VWI acquired at an isotropic resolution of 0.55 mm in 5 min without compromising quantitative vessel wall thickness measurement or diagnostic wall visualization. KEY POINTS: • CS VWI facilitates comprehensive visualization of intracranial and carotid vessel walls at an acquired isotropic resolution of 0.55 mm in a single 5-min scan. • CS VWI affords comparable vessel wall visualization and morphology measurement as PI VWI with a shortened acquisition time by 45%. • CS VWI alleviates the intensive trade-off between imaging resolution and scan time, and benefits the scan efficiency, motion robustness, and patient tolerance of high-resolution joint intracranial and carotid VWI.

T2STIR preparation for single-shot cardiovascular magnetic resonance myocardial edema imaging.

BACKGROUND: Myocardial edema in acute myocardial infarction (AMI) is commonly imaged using dark-blood short tau inversion recovery turbo spin echo (STIR-TSE) cardiovascular magnetic resonance (CMR). The technique is sensitive to cardiac motion and coil sensitivity variation, leading to myocardial signal nonuniformity and impeding reliable depiction of edematous tissues. T2-prepared balanced steady state free precession (T2p-bSSFP) imaging has been proposed, but its contrast is low, and averaging is commonly needed. T2 mapping is useful but requires a long scan time and breathholding. We propose here a single-shot magnetization prepared sequence that increases the contrast between edema and normal myocardium and apply it to myocardial edema imaging. METHODS: A magnetization preparation module (T2STIR) is designed to exploit the simultaneous elevation of T1 and T2 in edema to improve the depiction of edematous myocardium. The module tips magnetization down to the -z axis after T2 preparation. Transverse magnetization is sampled at the fat null point using bSSFP readout and allows for single-shot myocardial edema imaging. The sequence (T2STIR-bSSFP) was studied for its contrast behavior using simulation and phantoms. It was then evaluated on 7 healthy subjects and 7 AMI patients by comparing it to T2p-bSSFP and T2 mapping using the contrast-to-noise ratio (CNR) and the contrast ratio as performance indices. RESULTS: In simulation and phantom studies, T2STIR-bSSFP had improved contrast between edema and normal myocardium compared with the other two edema imaging techniques. In patients, the CNR of T2STIR-bSSFP was higher than T2p-bSSFP (5.9 ± 2.6 vs. 2.8 ± 2.0, P < 0.05) but had no significant difference compared with that of the T2 map (T2 map: 6.6 ± 3.3 vs. 5.9 ± 2.6, P = 0.62). The contrast ratio of T2STIR-bSSFP (2.4 ± 0.8) was higher than that of the T2 map (1.3 ± 0.1, P < 0.01) and T2p-bSSFP (1.4 ± 0.5, P < 0.05). CONCLUSION: T2STIR-bSSFP has improved contrast between edematous and normal myocardium compared with commonly used bSSFP-based edema imaging techniques. T2STIR-bSSFP also differentiates between fat that was robustly suppressed and fluids around the heart. The technique is useful for single-shot edema imaging in AMI patients.

Cardiovascular magnetic resonance evidence of myocardial fibrosis and its clinical significance in adolescent and adult patients with Ebstein's anomaly.

BACKGROUND: Myocardial fibrosis is a common pathophysiological process that is related to ventricular remodeling in congenital heart disease. However, the presence, characteristics, and clinical significance of myocardial fibrosis in Ebstein's anomaly have not been fully investigated. This study aimed to evaluate myocardial fibrosis using cardiovascular magnetic resonance (CMR) late gadolinium enhancement (LGE) and T1 mapping techniques, and to explore the significance of myocardial fibrosis in adolescent and adult patients with Ebstein's anomaly. METHODS: Forty-four consecutive patients with unrepaired Ebstein's anomaly (34.0 ± 16.2 years; 18 males), and an equal number of age- and gender-matched controls, were included. A comprehensive CMR protocol consisted of cine, LGE, and T1 mapping by modified Look-Locker inversion recovery (MOLLI) sequences were performed. Ventricular functional parameters, native T1, extracellular volume (ECV), and LGE were analyzed. Associations between myocardial fibrosis and disease severity, ventricular function, and NYHA classification were analyzed. RESULTS: LGE was found in 10 (22.7%) patients. Typical LGE in Ebstein's anomaly was located in the endocardium of the septum within the right ventricle (RV). The LV ECV of Ebstein's anomaly were significantly higher than those of the controls (30.0 ± 3.8% vs. 25.3 ± 2.3%, P < 0.001). An increased ECV was found to be independent of the existence of LGE. Positive LGE or higher ECV (≥30%) was associated with larger fRV volume, aRV volume, increased disease severity, and worse NYHA functional class. In addition, ECV was significantly correlated with the LV ejection fraction (P <  0.001). CONCLUSIONS: Both focal and diffuse myocardial fibrosis were observed in adolescent and adult patients with Ebstein's anomaly. Increased diffuse fibrosis is associated with worse LV function, increased Ebstein's severity, and worse clinical status.

Improved workflow for quantifying left ventricular function via cardiorespiratory-resolved analysis of free-breathing MR real-time cines.

PURPOSE: To evaluate the feasibility of a proposed cardiorespiratory-resolved analysis in left ventricular (LV) function quantification from real-time cines in a cohort of cardiac patients. MATERIALS AND METHODS: Electrocardiograph (ECG)-free free-breathing real-time cine imaging based on the balanced steady-state free precession technique was performed on short-axis slices of 20 cardiac patients at 3T. K-means cluster segmentation was used to delineate the endocardial contours, from which the LV centroid and cavity area were determined. Respiratory and cardiac signals were respectively resolved from the filtered LV centroid displacement and time-varied LV cavity area to identify end-expiratory end-diastolic (ED) and end-systolic (ES) images. The obtained LV cavity areas and derived volumetric function indices, including ED volume (EDV), ES volume (ESV), stroke volume (SV), and ejection fraction (EF), were compared with those measured from manual analysis using two-tailed paired Student's t-tests, linear regression analyses, and Bland-Altman plots. Interobserver variability was calculated. RESULTS: The LV cavity area was strongly correlated between the proposed and conventional manual methods (r > 0.87) for three representative slices at the base, middle ventricle, and apex. The average differences between the two methods were 0.66 ± 3.22 mL for EDV, -0.02 ± 2.68 mL for ESV, 0.67 ± 3.73 mL for SV, and 0.17 ± 2.30% for EF. All paired measures exhibited strong correlations (r > 0.96) without significant differences (P = 0.38-0.98). Acceptable interobserver variability (0.19-3.55%) and strong correlations (r > 0.96) were shown for all measures between the two observers. CONCLUSION: The proposed method is feasible for efficient measurement of LV function from real-time cines. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:905-914.

Assessing exercise cardiac reserve using real-time cardiovascular magnetic resonance.

BACKGROUND: Exercise cardiovascular magnetic resonance (ExCMR) has great potential for clinical use but its development has been limited by a lack of compatible equipment and robust real-time imaging techniques. We developed an exCMR protocol using an in-scanner cycle ergometer and assessed its performance in differentiating athletes from non-athletes. METHODS: Free-breathing real-time CMR (1.5T Aera, Siemens) was performed in 11 athletes (5 males; median age 29 [IQR: 28-39] years) and 16 age- and sex-matched healthy volunteers (7 males; median age 26 [interquartile range (IQR): 25-33] years). All participants underwent an in-scanner exercise protocol on a CMR compatible cycle ergometer (Lode BV, the Netherlands), with an initial workload of 25W followed by 25W-increment every minute. In 20 individuals, exercise capacity was also evaluated by cardiopulmonary exercise test (CPET). Scan-rescan reproducibility was assessed in 10 individuals, at least 7 days apart. RESULTS: The exCMR protocol demonstrated excellent scan-rescan (cardiac index (CI): 0.2 ± 0.5L/min/m2) and inter-observer (ventricular volumes: 1.2 ± 5.3mL) reproducibility. CI derived from exCMR and CPET had excellent correlation (r = 0.83, p < 0.001) and agreement (1.7 ± 1.8L/min/m2). Despite similar values at rest (P = 0.87), athletes had increased exercise CI compared to healthy individuals (at peak exercise: 12.2 [IQR: 10.2-13.5] L/min/m2 versus 8.9 [IQR: 7.5-10.1] L/min/m2, respectively; P < 0.001). Peak exercise CI, where image acquisition lasted 13-17 s, outperformed that at rest (c-statistics = 0.95 [95% confidence interval: 0.87-1.00] versus 0.48 [95% confidence interval: 0.23-0.72], respectively; P < 0.0001 for comparison) in differentiating athletes from healthy volunteers; and had similar performance as VO2max (c-statistics = 0.84 [95% confidence interval = 0.62-1.00]; P = 0.29 for comparison). CONCLUSIONS: We have developed a novel in-scanner exCMR protocol using real-time CMR that is highly reproducible. It may now be developed for clinical use for physiological studies of the heart and circulation.

Efficient method for analyzing MR real-time cines: Toward accurate quantification of left ventricular function.

BACKGROUND: To develop and assess an efficient method to identify end-expiratory end-diastolic (ED) and end-systolic (ES) images for accurate quantification of left ventricular (LV) function in real-time cine imaging. METHODS: ECG-free free-breathing real-time cine imaging was performed on short-axis slices of thirteen healthy volunteers at 3 Tesla. K-means cluster segmentation was applied to delineate the endocardial contour, from which the LV centroid and cavity area were determined in each cine image. LV centroid displacement along the superior-inferior direction was filtered to extract respiratory motion in each slice. End-expiratory ED and ES images were then identified and used for LV function quantification. Accuracy was evaluated with that measured from the slice-matched standard ECG-gated breathhold segmented cines using two-tail paired Student's t-tests, linear regression analyses and Bland-Altman plots. Intra- and interobserver variability was calculated for each imaging technique. RESULTS: Qualitatively, end-expiratory ED and ES images identified with the proposed method agreed with those determined by frame-by-frame visual inspection in 97.5% of cases (P > 0.05). Quantitatively, good agreement of LV function indices between the real-time cine and the standard segmented cine was observed with averaged differences of 0.1 ± 0.9 g for myocardium mass, -0.3 ± 1.0 mL for ED volume, 0.2 ± 1.2 mL for ES volume, -0.2 ± 1.3 mL for stroke volume, and -0.3 ± 0.8% for ejection fraction. Paired LV function values exhibited strong correlation (r ≥ 0.96) and no significant difference (P > 0.05). The real-time cine and the standard segmented cine showed similar intra- (1.2-3.3% and 1.1-2.8%, respectively) and interobserver variability (2.6-6.9% and 1.8-4.8%, respectively) with all P-values > 0.05. All the variability was comparable with published results. CONCLUSION: Compared with the laborious frame-by-frame visual inspection, as conventionally adopted, the proposed method is efficient in analyzing real-time cines for the accurate quantification of LV function without excessively manual interactions.

Development of Molecular Magnetic Resonance Imaging Tools for Longitudinal Tracking of Carotid Atherosclerotic Disease Using Fast Imaging with Steady-State Precession.

Identification of patients with high-risk asymptomatic carotid plaques remains a challenging but essential step in stroke prevention. Current selection criteria for intervention in carotid disease are still determined by symptomatology and degree of luminal stenosis. This strategy has been less effective in identifying the high-risk asymptomatic individual patients. Inflammation is the key factor that drives plaque instability causing clinical sequelae. Currently, there is no imaging tool in routine clinical practice to assess the inflammatory status within atherosclerotic plaques. Herein we describe the development of a novel molecular magnetic resonance imaging (MRI) strategy to interrogate plaque inflammation, and hence its vulnerability in vivo, using dual-targeted iron particle-based probes and fast imaging with steady-state precession (FISP) sequence, adding further prognostic information to luminal stenosis alone. A periarterial cuff was used to generate high-risk plaques at specific timepoints and location of the carotid artery in an apolipoprotein-E-deficient mouse model. Using this platform, we demonstrated that in vivo dual-targeted iron particles with enhanced FISP can (i) target and characterise high-risk vulnerable plaques and (ii) quantitatively report and track the inflammatory activity within carotid plaques longitudinally. This molecular imaging tool may permit (i) accurate monitoring of the risk of carotid plaques and (ii) timely identification of high-risk asymptomatic patients for prophylactic carotid intervention, achieving early stroke prevention.

Myocardial T2 mapping with respiratory navigator and automatic nonrigid motion correction.

Quantitative T2 mapping was recently shown to be superior to T2-weighted imaging in detecting T2 changes across myocardium. Pixel-wise T2 mapping is sensitive to misregistration between the images used to generate the parameter map. In this study, utility of two motion-compensation strategies-(i) navigator gating with prospective slice correction and (ii) nonrigid registration-was investigated for myocardial T2 mapping in short axis and horizontal long axis views. Navigator gating provides respiratory motion compensation, whereas registration corrects for residual cardiac and respiratory motion between images; thus, the two strategies provided complementary functions. When these were combined, respiratory-motion-induced T2 variability, as measured by both standard deviation and interquartile range, was comparable to that in breath-hold T2 maps. In normal subjects, this combined motion-compensation strategy increased the percentage of myocardium with T2 measured to be within normal range from 60.1% to 92.2% in short axis and 62.3% to 92.7% in horizontal long axis. The new motion-compensated T2 mapping technique, which combines navigator gating, prospective slice correction, and nonrigid registration to provide through-plane and in-plane motion correction, enables a method for fully automatic and robust free-breathing T2 mapping.

Shared velocity encoding: a method to improve the temporal resolution of phase-contrast velocity measurements.

Phase-contrast magnetic resonance imaging (PC-MRI) is used routinely to measure fluid and tissue velocity with a variety of clinical applications. Phase-contrast magnetic resonance imaging methods require acquisition of additional data to enable phase difference reconstruction, making real-time imaging problematic. Shared Velocity Encoding (SVE), a method devised to improve the effective temporal resolution of phase-contrast magnetic resonance imaging, was implemented in a real-time pulse sequence with segmented echo planar readout. The effect of SVE on peak velocity measurement was investigated in computer simulation, and peak velocities and total flow were measured in a flow phantom and in volunteers and compared with a conventional ECG-triggered, segmented k-space phase-contrast sequence as a reference standard. Computer simulation showed a 36% reduction in peak velocity error from 8.8 to 5.6% with SVE. A similar reduction of 40% in peak velocity error was shown in a pulsatile flow phantom. In the phantom and volunteers, volume flow did not differ significantly when measured with or without SVE. Peak velocity measurements made in the volunteers using SVE showed a higher concordance correlation (0.96) with the reference standard than non-SVE (0.87). The improvement in effective temporal resolution with SVE reconstruction has a positive impact on the precision and accuracy of real-time phase-contrast magnetic resonance imaging peak velocity measurements.

Assessment of carotid stenosis using three-dimensional T2-weighted dark blood imaging: Initial experience.

PURPOSE: To evaluate the use of a T2-weighted SPACE sequence (T2w-SPACE) to assess carotid stenosis via several methods and compare its performance with contrast-enhanced magnetic resonance angiography (ceMRA). MATERIALS AND METHODS: Fifteen patients with carotid atherosclerosis underwent dark blood (DB)-MRI using a 3D turbo spin echo with variable flip angles sequence (T2w-SPACE) and ceMRA. Images were coregistered and evaluated by two observers. Comparisons were made for luminal diameter, luminal area, degree of luminal stenosis (NASCET: North American Symptomatic Endarterectomy Trial; ECST: European Carotid Surgery Trial, and area stenosis), and vessel wall area. Degree of NASCET stenosis was clinically classified as mild (<50%), moderate (50%-69%), or severe (>69%). RESULTS: Excellent agreement was seen between ceMRA and T2w-SPACE and between observers for assessment of lumen diameter, lumen area, vessel wall area, and degree of NASCET stenosis (r > 0.80, P < 0.001). ECST stenosis was consistently higher than NASCET stenosis (48 ± 14% vs. 24 ± 22%, P < 0.001). Area stenosis (72 ± 2%) was significantly higher (P < 0.001) than both ESCT and NASCET stenosis. CONCLUSION: DB-MRI of carotid arteries using T2w-SPACE is clinically feasible. It provides accurate measurements of lumen size and degree of stenosis in comparison with ceMRA and offers a more reproducible measure of ECST stenosis than ceMRA.

A new approach to autocalibrated dynamic parallel imaging based on the Karhunen-Loeve transform: KL-TSENSE and KL-TGRAPPA.

TSENSE and TGRAPPA are autocalibrated parallel imaging techniques that can improve the temporal resolution and/or spatial resolution in dynamic magnetic resonance imaging applications. In its original form, TSENSE uses temporal low-pass filtering of the undersampled frames to create the sensitivity map. TGRAPPA uses a sliding-window moving average when finding the autocalibrating signals. Both filtering methods are suboptimal in the least-squares sense and may give rise to mismatches between the undersampled k-space raw data and the corresponding coil sensitivities. Such mismatches may result in aliasing artifacts when imaging patients with heavy breathing, as in real-time imaging of wall motion by MRI following a treadmill exercise stress test. In this study, we demonstrate the use of an optimal linear filter, i.e., the Karhunen-Loeve transform filter, to estimate the channel sensitivity for TSENSE and acquire the autocalibration signals for TGRAPPA. Phantom experiments show that the new reconstruction method has comparable signal-to-noise ratio performance to traditional TSENSE/TGRAPPA reconstruction. In vivo real-time cardiac cine experiments performed in five healthy volunteers post-exercise during rapid respiration show that the new method significantly reduces the chest wall aliasing artifacts caused by respiratory motion (P < 0.001).

A method to assess spatially variant noise in dynamic MR image series.

Accurate measurement of spatially variant noise in MR images acquired using parallel imaging techniques is challenging. Image-based noise measurement methods such as the subtraction method proposed by the National Electrical Manufacturers Association or the multiple acquisition method often cannot be applied in vivo due to motion and/or dynamic contrast changes. Based on the Karhunen-Loeve transform and random matrix theory, we propose a novel method to accurately assess the noise variance in image series bearing temporal redundancy. The method fits the probability density function of eigenvalues from the temporal covariance matrix of the image series to the Marcenko-Pastur distribution. The accuracy of our method was validated using numerical simulation and an MR noise measurement experiment. The ability of this method to derive the g-factor map of a static phantom was validated against the multiple acquisition method. The method was applied to in vivo cardiac and brain image series and the results agreed with subtraction and multiple acquisition methods, respectively. This new image-based noise measurement method provides a practical means of retrospectively evaluating the noise level and/or g-factor map from multiframe image series.

T1-weighted-SPACE dark blood whole body magnetic resonance angiography (DB-WBMRA): initial experience.

PURPOSE: To evaluate the feasibility of the dark blood fast spin echo (FSE) T1-weighted-Sampling Perfection with Application of optimized Contrasts using different flip angle Evolution (T1w-SPACE) sequence in assessing whole body arterial wall information from the extracranial carotids to the popliteal artery. MATERIALS AND METHODS: Twenty-eight subjects were subjected to noncontrast, dark blood whole body magnetic resonance angiography (DB-WBMRA) using a T1w-SPACE sequence optimized for each of the individual stations: carotid artery, thoracic aorta, abdominal aorta, and thigh/superficial femoral artery (SFA). Image quality/vessel wall visualization and the time required to image the four stations were evaluated. Two observers checked the reproducibility of vessel wall depiction by performing quantitative measurements in registered initial and repeat studies (six subjects) of vessel wall and lumen area at 17 locations along the arterial tree. RESULTS: In 25 of the 28 scanned subjects, dark blood arterial images acquired in approximately 1 hour total imaging time allowed whole body arterial vessel wall visualization. Quantitative measurements showed high correlation between the initial and repeat studies for each of the observers as well as high interobserver reproducibility (r > 0.95; P < 0.01). CONCLUSION: DB-WBMRA using T1w-SPACE is feasible and can be performed with a high degree of reliability.

Carotid arterial wall MRI at 3T using 3D variable-flip-angle turbo spin-echo (TSE) with flow-sensitive dephasing (FSD).

PURPOSE: To evaluate the effectiveness of flow-sensitive dephasing (FSD) magnetization preparation in improving blood signal suppression of three-dimensional (3D) turbo spin-echo (TSE) sequence (SPACE) for isotropic high-spatial-resolution carotid arterial wall imaging at 3T. MATERIALS AND METHODS: The FSD-prepared SPACE sequence (FSD-SPACE) was implemented by adding two identical FSD gradient pulses right before and after the first refocusing 180 degrees -pulse of the SPACE sequence in all three orthogonal directions. Nine healthy volunteers were imaged at 3T with SPACE, FSD-SPACE, and multislice T2-weighted 2D TSE coupled with saturation band (SB-TSE). Apparent carotid wall-lumen contrast-to-noise ratio (aCNR(w-l)) and apparent lumen area (aLA) at the locations with residual-blood (rb) signal shown on SPACE images were compared between SPACE and FSD-SPACE. Carotid aCNR(w-l) and lumen (LA) and wall area (WA) measured from FSD-SPACE were compared to those measured from SB-TSE. RESULTS: Plaque-mimicking flow artifacts identified in seven carotids on SPACE images were eliminated on FSD-SPACE images. The FSD preparation resulted in slightly reduced aCNR(w-l) (P = 0.025), but significantly improved aCNR between the wall and rb regions (P < 0.001) and larger aLA (P < 0.001). Compared to SB-TSE, FSD-SPACE offered comparable aCNR(w-l) with much higher spatial resolution, shorter imaging time, and larger artery coverage. The LA and WA measurements from the two techniques were in good agreement based on intraclasss correlation coefficient (0.988 and 0.949, respectively; P < 0.001) and Bland-Altman analyses. CONCLUSION: FSD-SPACE is a time-efficient 3D imaging technique for carotid arterial wall with superior spatial resolution and blood signal suppression.

T2 quantification for improved detection of myocardial edema.

BACKGROUND: T2-Weighted (T2W) magnetic resonance imaging (MRI) pulse sequences have been used to detect edema in patients with acute myocardial infarction and differentiate acute from chronic infarction. T2W sequences have suffered from several problems including (i) signal intensity variability caused by phased array coils, (ii) high signal from slow moving ventricular chamber blood that can mimic and mask elevated T2 in sub-endocardial myocardium, (iii) motion artifacts, and (iv) the subjective nature of T2W image interpretation. In this work we demonstrate the advantages of a quantitative T2 mapping technique to accurately and reliably detect regions of edematous myocardial tissue without the limitations of qualitative T2W imaging. METHODS: Methods of T2 mapping were evaluated on phantoms; the best of these protocols was then optimized for in vivo imaging. The optimized protocol was used to study the spatial, view-dependent, and inter-subject variability and motion sensitivity in healthy subjects. Using the insights gained from this, the utility of T2 mapping was demonstrated in a porcine model of acute myocardial infarction (AMI) and in three patients with AMI. RESULTS: T2-prepared SSFP demonstrated greater accuracy in estimating the T2 of phantoms than multi-echo turbo spin echo. The T2 of human myocardium was found to be 52.18 +/- 3.4 ms (range: 48.96 ms to 55.67 ms), with variability between subjects unrelated to heart rate. Unlike T2W images, T2 maps did not show any signal variation due to the variable sensitivity of phased array coils and were insensitive to cardiac motion. In the three pigs and three patients with AMI, the T2 of the infarcted region was significantly higher than that of remote myocardium. CONCLUSION: Quantitative T2 mapping addresses the well-known problems associated with T2W imaging of the heart and offers the potential for increased accuracy in the detection of myocardial edema.

Application of the Karhunen-Loeve transform temporal image filter to reduce noise in real-time cardiac cine MRI.

Real-time dynamic magnetic resonance imaging (MRI) typically sacrifices the signal-to-noise ratio (SNR) to achieve higher spatial and temporal resolution. Spatial and/or temporal filtering (e.g., low-pass filtering or averaging) of dynamic images improves the SNR at the expense of edge sharpness. We describe the application of a temporal filter for dynamic MR image series based on the Karhunen-Loeve transform (KLT) to remove random noise without blurring stationary or moving edges and requiring no training data. In this paper, we present several properties of this filter and their effects on filter performance, and propose an automatic way to find the filter cutoff based on the autocorrelation of the eigenimages. Numerical simulation and in vivo real-time cardiac cine MR image series spanning multiple cardiac cycles acquired using multi-channel sensitivity-encoded MRI, i.e., parallel imaging, are used to validate and demonstrate these properties. We found that in this application, the noise standard deviation was reduced to 42% of the original with no apparent image blurring by using the proposed filter cutoff. Greater noise reduction can be achieved by increasing the length of the image series. This advantage of KLT filtering provides flexibility in the form of another scan parameter to trade for SNR.

Platelet inhibition to target reperfusion injury trial: Rationale and study design.

BACKGROUND: In ST-segment elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PPCI), current oral P2Y12 platelet inhibitors do not provide maximal platelet inhibition at the time of reperfusion. Furthermore, administration of cangrelor prior to reperfusion has been shown in pre-clinical studies to reduce myocardial infarct (MI) size. Therefore, we hypothesize that cangrelor administered prior to reperfusion in STEMI patients will reduce the incidence of microvascular obstruction (MVO) and limit MI size in STEMI patients treated with PPCI. METHODS: The platelet inhibition to target reperfusion injury (PITRI) trial, is a phase 2A, multi-center, double-blinded, randomized controlled trial, in which 210 STEMI patients will be randomized to receive either an intravenous (IV) bolus of cangrelor (30 µg/kg) followed by a 120-minute infusion (4 µg/kg/min) or matching saline placebo, initiated prior to reperfusion (NCT03102723). RESULTS: The study started in October 2017 and the anticipated end date would be July 2020. The primary end-point will be MI size quantified by cardiovascular magnetic resonance (CMR) on day 3 post-PPCI. Secondary endpoints will include markers of reperfusion, incidence of MVO, MI size, and adverse left ventricular remodeling at 6 months, and major adverse cardiac and cerebrovascular events. SUMMARY: The aim of the PITRI trial is to assess whether cangrelor administered prior to reperfusion would reduce acute MI size and MVO, as assessed by CMR.

Rapid phase-modulated water excitation steady-state free precession for fat suppressed cine cardiovascular MR.

BACKGROUND: The purpose of this article is to describe a steady-state free precession (SSFP) sequence for fat suppressed cine cardiovascular magnetic resonance (CMR). A rapid phase-modulated binomial water excitation (WE) pulse is utilized to minimize repetition time and acquisition time. METHODS: Three different water-excitation pulses were combined with cine-SSFP for evaluation. The frequency response of each sequence was simulated and examined in phantom imaging studies. The ratio of fat to water signal amplitude was measured in phantoms to evaluate the fat suppression capabilities of each method. Six volunteers underwent CMR of the heart at 1.5T to compare retrospectively-gated cine-SSFP with and without water excitation. The ratio of fat to myocardium signal amplitude was measured for conventional cine-SSFP and phase-modulated WE-SSFP. The proposed WE-SSFP method was tested in one patient referred for CMR to characterize a cardiac mass. RESULTS AND DISCUSSION: The measured frequency response in a phantom corresponded to the numerical Bloch equation simulation demonstrating the widened stop-band around the fat resonant frequency for all water-excitation pulses tested. In vivo measurements demonstrated that a rapid, phase-modulated water excitation pulse significantly reduced the signal amplitude ratio of fat to myocardium from 6.92 +/- 2.9 to 0.8 +/- 0.13 (mean +/- SD) without inducing any perceptible artifacts in SSFP cine CMR. CONCLUSION: Fat suppression can be achieved in SSFP cine CMR while maintaining steady-state equilibrium using rapid, phase modulated, binomial water-excitation pulses.