Assessment of Papillary Muscle Infarction with Dark-Blood Delayed Enhancement Cardiac MRI in Canines and Humans.

Background The relationship between papillary muscle infarction (papMI) and the culprit coronary lesion has not been fully investigated. Delayed enhancement cardiac MRI may detect papMI, yet its accuracy is unknown. Flow-independent dark-blood delayed enhancement (FIDDLE) cardiac MRI has been shown to improve the detection of myocardial infarction adjacent to blood pool. Purpose To assess the diagnostic performance of delayed enhancement and FIDDLE cardiac MRI for the detection of papMI, and to investigate the prevalence of papMI and its relationship to the location of the culprit coronary lesion. Materials and Methods A prospective canine study was used to determine the accuracy of conventional delayed enhancement imaging and FIDDLE imaging for detection of papMI, with pathology-based findings as the reference standard. Participants with first-time myocardial infarction with a clear culprit lesion at coronary angiography were prospectively enrolled at a single hospital from 2015 to 2018 and compared against control participants with low Framingham risk scores. In canines, diagnostic accuracy was calculated for delayed enhancement and FIDDLE imaging. Results In canines (n = 27), FIDDLE imaging was more sensitive (100% [23 of 23] vs 57% [13 of 23], P < .001) and accurate (100% [54 of 54] vs 80% [43 of 54], P = .01) than delayed enhancement imaging for detection of papMI. In 43 participants with myocardial infarction (mean age, 56 years ± 16 [SD]; 28 men), the infarct-related artery was the left anterior descending coronary artery (LAD), left circumflex coronary artery (LCX), and right coronary artery in 47% (20 of 43), 26% (11 of 43), and 28% (12 of 43), respectively. The prevalence of anterior papMI was lower than posterior papMI (37% [16 of 43 participants] vs 44% [19 of 43 participants]) despite more LAD culprit lesions. Culprits leading to papMI were restricted to a smaller "at-risk" portion of the coronary tree for anterior papMI (subtended first diagonal branch of the LAD or first marginal branch of the LCX) compared with posterior (subtended posterior descending artery or third obtuse marginal branch of the LCX). Culprits within these at-risk portions were predictive of papMI at a similar rate (anterior, 83% [15 of 18 participants] vs posterior, 86% [18 of 21 participants]). Conclusion Flow-independent dark-blood delayed enhancement cardiac MRI, unlike conventional delayed enhancement cardiac MRI, was highly accurate in the detection of papillary muscle infarction (papMI). Anterior papMI was less prevalent than posterior papMI, most likely due to culprit lesions being restricted to a smaller portion of the coronary tree rather than because of redundant, dual vascular supply. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Kawel-Boehm and Bremerich in this issue.

Assessment of myocardial lipomatous metaplasia using an optimized out-of-phase cine steady-state free-precession sequence: Validation and clinical implementation.

Myocardial lipomatous metaplasia, which can serve as substrate for ventricular arrhythmias, is usually composed of regions in which there is an admixture of fat and nonfat tissue. Although dedicated sequences for the detection of fat are available, it would be time-consuming and burdensome to routinely use these techniques to image the entire heart of all patients as part of a typical cardiac MRI exam. Conventional steady-state free-precession (SSFP) cine imaging is insensitive to detecting myocardial regions with partial fatty infiltration. We developed an optimization process for SSFP imaging to set fat signal consistently "out-of-phase" with water throughout the heart, so that intramyocardial regions with partial volume fat would be detected as paradoxically dark regions. The optimized SSFP sequence was evaluated using a fat phantom, through simulations, and in 50 consecutive patients undergoing clinical cardiac MRI. Findings were validated using standard Dixon gradient-recalled-echo (GRE) imaging as the reference. Phantom studies of test tubes with diverse fat concentrations demonstrated good agreement between measured signal intensity and simulated values calculated using Bloch equations. In patients, a line of signal cancellation at the interface between myocardium and epicardial fat was noted in all cases, confirming that SSFP images were consistently out-of-phase throughout the entire heart. Intramyocardial dark regions identified on out-of-phase SSFP images were entirely dark throughout in 33 patients (66%) and displayed an India-ink pattern in 17 (34%). In all cases, dark intramyocardial regions were also seen in the same locations on out-of-phase GRE and were absent on in-phase GRE, confirming that these regions represent areas with partial fat. In conclusion, if appropriately optimized, SSFP cine imaging allows for consistent detection of myocardial fatty metaplasia in patients undergoing routine clinical cardiac MRI without the need for additional image acquisitions using dedicated fat-specific sequences.

Double spectral attenuated inversion recovery (DSPAIR)-an efficient fat suppression technique for late gadolinium enhancement at 3 tesla.

Despite clinical use of late gadolinium enhancement (LGE) for two decades, an efficient, robust fat suppression (FS) technique still does not exist for this CMR mainstay. In ischemic and non-ischemic heart disease, differentiating fibrotic tissue from infiltrating and adjacent fat is crucial. Multiple groups have independently developed an FS technique for LGE, double spectral attenuated inversion recovery (DSPAIR), but no comprehensive evaluation was performed. This study aims to fill this gap. DSPAIR uses two SPAIR pulses and one non-selective IR pulse to enable FS LGE, including compatibility with phase sensitive inversion recovery (PSIR). We implemented a magnitude (MAGN) and a PSIR variant and compared them with LGE without FS (CONTROL) and with spectral presaturation with inversion recovery (SPIR) in simulations, phantoms, and patients. Fat magnetization by SPIR, MAGN DSPAIR, and PSIR DSPAIR was simulated as a function of pulse B1 , readout (RO) pulse number, and fat TI . A phantom with fat, fibrosis, and myocardium compartments was imaged using all FS methods and modifying pulse B1 , RO pulse number, and heart rate. Signal was measured in SNR units. Fat, myocardium, and fibrosis SNR and fibrosis-to-fat CNR were obtained. Patient images were acquired with all FS techniques. Fat, myocardium, and fibrosis SNR, fibrosis-to-fat CNR, and image and FS quality were assessed. In the phantom, both DSPAIR variants provided superior FS compared with SPIR, independent of heart rate and RO pulse number. MAGN DSPAIR reduced fat signal by 99% compared with CONTROL, PSIR DSPAIR by 116%, and SPIR by 67% (25 RO pulses). In patients, both DSPAIR variants substantially reduced fat signal (MAGN DSPAIR by 87.1% ± 10.0%, PSIR DSPAIR by 130.5% ± 36.3%), but SPIR did not (35.8% ± 25.5%). FS quality was good to excellent for MAGN and PSIR DSPAIR, and moderate to poor for SPIR. DSPAIR provided highly effective FS across a wide range of parameters. PSIR DSPAIR performed best.

Comparison of magnetization transfer-preparation and T2-preparation for dark-blood delayed-enhancement imaging.

Recently developed dark-blood techniques such as Flow-Independent Dark-blood DeLayed Enhancement (FIDDLE) allow simultaneous visualization of tissue contrast-enhancement and blood-pool suppression. Critical to FIDDLE is the magnetization preparation, which accentuates differences between myocardium and blood-pool. Here, we compared magnetization transfer (MT)-preparation and T2-preparation for use with FIDDLE. Variants of FIDDLE were developed with MT- or T2-preparation modules and tested in 35 patients (11 at 1.5 T, 24 at 3 T). Images were acquired with each FIDDLE variant in an interleaved fashion 10 minutes after gadolinium administration with otherwise identical acquisition parameters. Images were visually and quantitatively assessed for artifacts and differences in right ventricle to left ventricle (RV-to-LV) blood-pool suppression. Bright artifacts, reflecting incomplete blood-pool suppression, were frequently observed in the left atrium with T2-preparation FIDDLE at 1.5 and 3 T (82% and up to 100% of patients, respectively). MT-preparation FIDDLE resulted in fewer patients with artifacts (0% at 1.5 T, 22% at 3 T; P < .01). Left atrial blood-pool signal was significantly more homogeneous with MT-preparation than with T2-preparation at 1.5 and 3 T (P < .001 for all comparisons). Visibly different RV-to-LV blood-pool suppression was observed with T2-preparation in 36% of patients at 1.5 T and up to 94% at 3 T. In these patients, RV blood-pool signal was elevated, reducing the conspicuity of the myocardial-RV blood-pool border. Conversely, there were no visible differences in RV-to-LV blood-pool suppression with MT-preparation. Quantitative assessment of differences in blood-pool suppression and blood-pool artifacts was consistent with visual analyses. We conclude that for dark blood-blood delayed-enhancement imaging of the heart, MT-preparation results in fewer bright blood-pool artifacts and more uniform blood-pool suppression than T2-preparation.

Suppression of ghost artifacts arising from long T1 species in segmented inversion-recovery imaging.

PURPOSE: We demonstrate an improved segmented inversion-recovery sequence that suppresses ghost artifacts arising from tissues with long T1 ( > 1.5 s). THEORY AND METHODS: Long T1 species such as pericardial fluid can create bright ghost artifacts in segmented, inversion-recovery MRI because of oscillations in longitudinal magnetization between segments. A single dummy acquisition at the beginning of the sequence can reduce oscillations; however, its effectiveness in suppressing long T1 artifacts is unknown. In this study, we systematically evaluated several test sequences, including a prototype (saturation post-pulse readout to eliminate spurious signal: SPPRESS) in simulations, phantoms, and patients. RESULTS: SPPRESS reduced artifact signal 90% ± 25% and 74% ± 28% compared with Control and Single-Dummy methods in phantoms. SPPRESS performed well at 1.5 Tesla (T) and 3T, with steady-state free precession (SSFP) and fast low-angle shot (FLASH) readout, with conventional and phase-sensitive reconstruction, and over a range of physiologic heart rates. A review of 100 consecutive clinical cardiac MRI scans revealed large fluid collections (eg, regions with long T1 ) in 14% of patients. In a prospectively enrolled cohort of 16 patients with visible long T1 fluids, SPPRESS appreciably reduced artifacts in all cases compared with Control and Single-Dummy methods. CONCLUSION: We developed and validated a new robust method, SPPRESS, for reducing artifacts due to long T1 species across a wide range of imaging and physiologic conditions. Magn Reson Med 78:1442-1451, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Relationship of T2-Weighted MRI Myocardial Hyperintensity and the Ischemic Area-At-Risk.

RATIONALE: After acute myocardial infarction (MI), delineating the area-at-risk (AAR) is crucial for measuring how much, if any, ischemic myocardium has been salvaged. T2-weighted MRI is promoted as an excellent method to delineate the AAR. However, the evidence supporting the validity of this method to measure the AAR is indirect, and it has never been validated with direct anatomic measurements. OBJECTIVE: To determine whether T2-weighted MRI delineates the AAR. METHODS AND RESULTS: Twenty-one canines and 24 patients with acute MI were studied. We compared bright-blood and black-blood T2-weighted MRI with images of the AAR and MI by histopathology in canines and with MI by in vivo delayed-enhancement MRI in canines and patients. Abnormal regions on MRI and pathology were compared by (a) quantitative measurement of the transmural-extent of the abnormality and (b) picture matching of contours. We found no relationship between the transmural-extent of T2-hyperintense regions and that of the AAR (bright-blood-T2: r=0.06, P=0.69; black-blood-T2: r=0.01, P=0.97). Instead, there was a strong correlation with that of infarction (bright-blood-T2: r=0.94, P<0.0001; black-blood-T2: r=0.95, P<0.0001). Additionally, contour analysis demonstrated a fingerprint match of T2-hyperintense regions with the intricate contour of infarcted regions by delayed-enhancement MRI. Similarly, in patients there was a close correspondence between contours of T2-hyperintense and infarcted regions, and the transmural-extent of these regions were highly correlated (bright-blood-T2: r=0.82, P<0.0001; black-blood-T2: r=0.83, P<0.0001). CONCLUSION: T2-weighted MRI does not depict the AAR. Accordingly, T2-weighted MRI should not be used to measure myocardial salvage, either to inform patient management decisions or to evaluate novel therapies for acute MI.

Motion and flow insensitive adiabatic T2 -preparation module for cardiac MR imaging at 3 Tesla.

A versatile method for generating T2 -weighting is a T2 -preparation module, which has been used successfully for cardiac imaging at 1.5T. Although it has been applied at 3T, higher fields (B0 ≥ 3T) can degrade B0 and B1 homogeneity and result in nonuniform magnetization preparation. For cardiac imaging, blood flow and cardiac motion may further impair magnetization preparation. In this study, a novel T2 -preparation module containing multiple adiabatic B1 -insensitive refocusing pulses is introduced and compared with three previously described modules [(a) composite MLEV4, (b) modified BIR-4 (mBIR-4), and (c) Silver-Hoult-pair]. In the static phantom, the proposed module provided similar or better B0 and B1 insensitivity than the other modules. In human subjects (n = 21), quantitative measurement of image signal coefficient of variation, reflecting overall image inhomogeneity, was lower for the proposed module (0.10) than for MLEV4 (0.15, P < 0.0001), mBIR-4 (0.27, P < 0.0001), and Silver-Hoult-pair (0.14, P = 0.001) modules. Similarly, qualitative analysis revealed that the proposed module had the best image quality scores and ranking (both, P < 0.0001). In conclusion, we present a new T2 -preparation module, which is shown to be robust for cardiac imaging at 3T in comparison with existing methods.

Native T1 Mapping for the Diagnosis of Myocardial Fibrosis in Patients With Chronic Myocardial Infarction.

BACKGROUND: Myocardial fibrosis is a fundamental process in cardiac injury. Cardiac magnetic resonance native T1 mapping has been proposed for diagnosing myocardial fibrosis without the need for gadolinium contrast. However, recent studies suggest that T1 measurements can be erroneous in the presence of intramyocardial fat. OBJECTIVES: The purpose of this study was to investigate whether the presence of fatty metaplasia affects the accuracy of native T1 maps for the diagnosis of myocardial replacement fibrosis in patients with chronic myocardial infarction (MI). METHODS: Consecutive patients (n = 312) with documented chronic MI (>6 months old) and controls without MI (n = 50) were prospectively enrolled. Presence and size of regions with elevated native T1 and infarction were quantitatively determined (mean + 5SD) on modified look-locker inversion-recovery and delayed-enhancement images, respectively, at 3.0-T. The presence of fatty metaplasia was determined using an out-of-phase steady-state free-precession cine technique and further verified with standard fat-water Dixon methods. RESULTS: Native T1 mapping detected chronic MI with markedly higher sensitivity in patients with fatty metaplasia than those without fatty metaplasia (85.6% vs 13.3%) with similar specificity (100% vs 98.9%). In patients with fatty metaplasia, the size of regions with elevated T1 significantly underestimated infarct size and there was a better correlation with fatty metaplasia size than infarct size (r = 0.76 vs r = 0.49). In patients without fatty metaplasia, most of the modest elevation in T1 appeared to be secondary to subchronic infarcts that were 6 to 12 months old; the T1 of infarcts >12 months old was not different from noninfarcted myocardium. CONCLUSIONS: Native T1 mapping is poor at detecting replacement fibrosis but may indirectly detect chronic MI if there is associated fatty metaplasia. Native T1 mapping for the diagnosis and characterization of myocardial fibrosis is unreliable.

Noninvasive cineangiography by magnetic resonance global coherent free precession.

Cardiovascular disease is primarily diagnosed using invasive X-ray cineangiography. Here we introduce a new concept in magnetic resonance imaging (MRI) that, for the first time, produces similar images noninvasively and without a contrast agent. Protons in moving blood are 'tagged' every few milliseconds as they travel through an arbitrary region in space. Simultaneous with ongoing tagging of new blood, previously tagged blood is maintained in a state of global coherent free precession (GCFP), which allows acquisition of consecutive movie frames as the heart pushes blood through the vascular bed. Body tissue surrounding the moving blood is never excited and therefore remains invisible. In 18 subjects, pulsating blood could be seen flowing through three-dimensional (3D) space for distances of up to 16 cm outside the stationary excitation region. These data underscore that our approach noninvasively characterizes both anatomy and blood flow in a manner directly analogous to invasive procedures.

Dark-Blood Delayed Enhancement Cardiac Magnetic Resonance of Myocardial Infarction.

OBJECTIVES: This study introduced and validated a novel flow-independent delayed enhancement technique that shows hyperenhanced myocardium while simultaneously suppressing blood-pool signal. BACKGROUND: The diagnosis and assessment of myocardial infarction (MI) is crucial in determining clinical management and prognosis. Although delayed enhancement cardiac magnetic resonance (DE-CMR) is an in vivo reference standard for imaging MI, an important limitation is poor delineation between hyperenhanced myocardium and bright LV cavity blood-pool, which may cause many infarcts to become invisible. METHODS: A canine model with pathology as the reference standard was used for validation (n = 22). Patients with MI and normal controls were studied to ascertain clinical performance (n = 31). RESULTS: In canines, the flow-independent dark-blood delayed enhancement (FIDDLE) technique was superior to conventional DE-CMR for the detection of MI, with higher sensitivity (96% vs. 85%, respectively; p = 0.002) and accuracy (95% vs. 87%, respectively; p = 0.01) and with similar specificity (92% vs, 92%, respectively; p = 1.0). In infarcts that were identified by both techniques, the entire length of the endocardial border between infarcted myocardium and adjacent blood-pool was visualized in 33% for DE-CMR compared with 100% for FIDDLE. There was better agreement for FIDDLE-measured infarct size than for DE-CMR infarct size (95% limits-of-agreement, 2.1% vs. 5.5%, respectively; p < 0.0001). In patients, findings were similar. FIDDLE demonstrated higher accuracy for diagnosis of MI than DE-CMR (100% [95% confidence interval [CI]: 89% to 100%] vs. 84% [95% CI: 66% to 95%], respectively; p = 0.03). CONCLUSIONS: The study introduced and validated a novel CMR technique that improves the discrimination of the border between infarcted myocardium and adjacent blood-pool. This dark-blood technique provides diagnostic performance that is superior to that of the current in vivo reference standard for the imaging diagnosis of MI.

Noninvasive assessment of blood flow based on magnetic resonance global coherent free precession.

BACKGROUND: Magnetic resonance global coherent free precession (GCFP) is a new technique that produces cine projection angiograms directly analogous to those of x-ray angiography noninvasively and without a contrast agent. In this study, we compared GCFP blood flow with "gold standards" to determine the accuracy of noninvasive GCFP blood flow measurements. METHODS AND RESULTS: The relationship between GCFP blood flow and true blood flow defined by invasive ultrasonic flow probe and by phase contrast velocity encoded MRI (VENC) was studied in anesthetized dogs (n=6). Blood flow was controlled by use of a hydraulic occluder around the left iliac artery. GCFP images were acquired by selectively exciting the abdominal aorta and visualizing temporal blood flow into the iliac arteries. GCFP flow was similar to ultrasonic blood flow at baseline (131.3+/-44.8 versus 114.8+/-34.2 mL/min), during occlusion (10.8+/-5.1 versus 6.5+/-7.2 mL/min), during reactive hyperemia (191.4+/-100.7 versus 260.3+/-138.7 mL/min), during the new resting state (135.5+/-52.4 versus 117.8+/-24.1 mL/min), and during partial occlusion (61.4+/-36.4 versus 49.3+/-13.1 mL/min, P=NS for all). Results comparing GCFP flow with VENC were similar. Statistical analysis revealed that GCFP flow was related to mean blood flow assessed by the flow probe (P<0.0001) and by VENC (P<0.0001). In the control right iliac artery, conversely, GCFP measurements were unaffected throughout all left iliac interventions (P=NS). CONCLUSIONS: GCFP blood flow is linearly related to true blood flow for a straight, cylindrical blood vessel without branches. Although more complex geometries imply a qualitative rather than a quantitative relationship, the data nevertheless suggest that GCFP may serve as the basis for a new form of noninvasive stress testing.

Myocardial magnetic resonance imaging contrast agent concentrations after reversible and irreversible ischemic injury.

BACKGROUND: Discrepant reports have been published recently regarding the relationship of contrast-enhanced magnetic resonance image intensities to reversible and irreversible ischemic injury. Unlike image intensities, contrast agent concentrations provide data independent of the MRI technique. We used electron probe x-ray microanalysis (EPXMA) to simultaneously examine concentrations of Gd, Na, P, S, Cl, K, and Ca over a range of myocardial injuries. Methods and Results- Reversible and irreversible injury were studied in 38 rabbits divided into 4 groups defined by occlusion and reperfusion time, as well as time the animals were euthanized. Gd-DTPA was administered, and the hearts were excised and rapidly frozen, cryosectioned, freeze-dried, and examined by EPXMA in up to 3 regions: remote, infarcted, and at risk but not infarcted. Infarcted regions were defined by anti-myoglobin antibody or triphenyltetrazolium chloride staining. Regions at risk were defined by fluorescent microparticles administered during occlusion. Compared with remote regions, in acutely infarcted regions, Gd was increased (235+/-24%, P<0.005) in the same 50 x 100-microm areas in which Na was increased (154+/-5%, P<0.001) and K was decreased (52+/-8%, P<0.001). Similarly, in chronically infarcted regions, Gd was increased (472+/-78%, P<0.001) in areas in which Na was increased (332+/-28%, P<0.001) and K was decreased (47+/-5%, P<0.001). Also compared with remote regions, however, concentrations of Gd, Na, and K were not elevated after reperfusion in regions that were at risk but not infarcted (P=NS). CONCLUSIONS: Regional elevations in myocardial MRI contrast agent concentrations are exclusively associated with irreversible ischemic injury defined histologically and by regional electrolyte concentrations.

Magnetic resonance water proton relaxation in protein solutions and tissue: T(1rho) dispersion characterization.

BACKGROUND: Image contrast in clinical MRI is often determined by differences in tissue water proton relaxation behavior. However, many aspects of water proton relaxation in complex biological media, such as protein solutions and tissue are not well understood, perhaps due to the limited empirical data. PRINCIPAL FINDINGS: Water proton T(1), T(2), and T(1rho) of protein solutions and tissue were measured systematically under multiple conditions. Crosslinking or aggregation of protein decreased T(2) and T(1rho), but did not change high-field T(1). T(1rho) dispersion profiles were similar for crosslinked protein solutions, myocardial tissue, and cartilage, and exhibited power law behavior with T(1rho)(0) values that closely approximated T(2). The T(1rho) dispersion of mobile protein solutions was flat above 5 kHz, but showed a steep curve below 5 kHz that was sensitive to changes in pH. The T(1rho) dispersion of crosslinked BSA and cartilage in DMSO solvent closely resembled that of water solvent above 5 kHz but showed decreased dispersion below 5 kHz. CONCLUSIONS: Proton exchange is a minor pathway for tissue T(1) and T(1rho) relaxation above 5 kHz. Potential models for relaxation are discussed, however the same molecular mechanism appears to be responsible across 5 decades of frequencies from T(1rho) to T(1).

Combining spin echoes with gradient echoes in the context of the global coherent free precession pulse sequence.

To extend the signal longevity of magnetically excited spins in flowing fluids while in a state of global coherent free precession (GCFP), a refocusing radiofrequency (RF) pulse and bipolar gradient waveforms were combined with the GCFP sequence. The data demonstrate that RF refocusing in the presence of flowing blood is possible, but the improvement in signal amplitude depends on the static magnetic field homogeneity along the direction of motion and the displacement of the spins between the excitation and the RF refocusing pulse, as well as displacement during subsequent RF refocusing pulses. The least amount of phase dispersion and thus the longest lasting signal is obtained with the shortest echo spacing where only one line of data is recorded between two RF refocusing pulses. This approach was successfully used in a phantom and in vivo to image fast and slow blood flow. Depending on the experimental conditions, signal persistence is improved significantly compared to playing the same sequence without RF refocusing, but the improvement is limited by the product of blood flow velocity and the time between RF refocusing pulses.