MRI Accurately Visualizes RF Ablation Delivery Targeted to MRI-Defined Arrhythmia Substrates in the Left Ventricle.

OBJECTIVE: Investigate the capacity of MRI to evaluate efficacy of radiofrequency (RF) ablations delivered to MRI-defined arrhythmogenic substrates. METHODS: Baseline MRI was performed at 3T including 3D LGE in a swine model of chronic myocardial infarct (N=8). MRI-derived maps of scar and heterogeneous tissue channels (HTCs) were generated using ADAS 3D. Animals underwent electroanatomic mapping and ablation of the left ventricle in CARTO3, guided by MRI-derived scar maps. Post-ablation MRI (in vivo at 3T in 5/8 animals; ex vivo at 1.5T in 3/8) included 3D native T1-weighted IR-SPGR (TI=700-800ms) to visualize RF lesions. T1-derived RF lesions were compared against excised tissue. The locations of T1-derived RF lesions were compared against CARTO ablation tags, and segment-wise sensitivity and specificity of lesion detection were calculated within the AHA 17-segment model. RESULTS: RF lesions were clearly visualized in HTCs, scar, and myocardium. Ablation patterns delivered in CARTO matched T1-derived RF lesion patterns with high sensitivity (88.9%) and specificity (94.7%), and were closely matched in registered MR-EP data sets, with a displacement of 5.4 ±3.8mm (N=152 ablation tags). CONCLUSION: Integrating MRI into ablative procedures for RF lesion assessment is feasible. Patterns of RF lesions created using a standard 3D EAM system are accurately reflected by MRI visualization in healthy myocardium, scar, and HTCs comprising the MRI-defined arrhythmia substrate. SIGNIFICANCE: MRI visualization of RF lesions can provide near-immediate (<24h) assessment of ablation, potentially indicating whether critical MRI-defined ventricular tachycardia substrates have been adequately ablated.

Evaluating a novel accelerated free-breathing late gadolinium enhancement imaging sequence for assessment of myocardial injury.

INTRODUCTION: Cardiac magnetic resonance imaging (MRI), including late gadolinium enhancement (LGE), plays an important role in the diagnosis and prognostication of ischemic and non-ischemic myocardial injury. Conventional LGE sequences require patients to perform multiple breath-holds and require long acquisition times. In this study, we compare image quality and assessment of myocardial LGE using an accelerated free-breathing sequence to the conventional standard-of-care sequence. METHODS: In this prospective cohort study, a total of 41 patients post Coronavirus 2019 (COVID-19) infection were included. Studies were performed on a 1.5 Tesla scanner with LGE imaging acquired using a conventional inversion recovery rapid gradient echo (conventional LGE) sequence followed by the novel accelerated free-breathing (FB-LGE) sequence. Image quality was visually scored (ordinal scale from 1 to 5) and compared between conventional and free-breathing sequences using the Wilcoxon rank sum test. Presence of per-segment LGE was identified according to the American Heart Association 16-segment myocardial model and compared across both conventional LGE and FB-LGE sequences using a two-sided chi-square test. The perpatient LGE extent was also evaluated using both sequences and compared using the Wilcoxon rank sum test. Interobserver variability in detection of per-segment LGE and per-patient LGE extent was evaluated using Cohen's kappa statistic and interclass correlation (ICC), respectively. RESULTS: The mean acquisition time for the FB-LGE sequence was 17 s compared to 413 s for the conventional LGE sequence (P < 0.001). Assessment of image quality was similar between both sequences (P = 0.19). There were no statistically significant differences in LGE assessed using the FB-LGE versus conventional LGE on a per-segment (P = 0.42) and per-patient (P = 0.06) basis. Interobserver variability in LGE assessment for FB-LGE was good for per-segment (= 0.71) and per-patient extent (ICC = 0.92) analyses. CONCLUSIONS: The accelerated FB-LGE sequence performed comparably to the conventional standard-of-care LGE sequence in a cohort of patients post COVID-19 infection in a fraction of the time and without the need for breath-holding. Such a sequence could impact clinical practice by increasing cardiac MRI throughput and accessibility for frail or acutely ill patients unable to perform breath-holding.

Motion-compensated T1 mapping in cardiovascular magnetic resonance imaging: a technical review.

T1 mapping is becoming a staple magnetic resonance imaging method for diagnosing myocardial diseases such as ischemic cardiomyopathy, hypertrophic cardiomyopathy, myocarditis, and more. Clinically, most T1 mapping sequences acquire a single slice at a single cardiac phase across a 10 to 15-heartbeat breath-hold, with one to three slices acquired in total. This leaves opportunities for improving patient comfort and information density by acquiring data across multiple cardiac phases in free-running acquisitions and across multiple respiratory phases in free-breathing acquisitions. Scanning in the presence of cardiac and respiratory motion requires more complex motion characterization and compensation. Most clinical mapping sequences use 2D single-slice acquisitions; however newer techniques allow for motion-compensated reconstructions in three dimensions and beyond. To further address confounding factors and improve measurement accuracy, T1 maps can be acquired jointly with other quantitative parameters such as T2, T2∗, fat fraction, and more. These multiparametric acquisitions allow for constrained reconstruction approaches that isolate contributions to T1 from other motion and relaxation mechanisms. In this review, we examine the state of the literature in motion-corrected and motion-resolved T1 mapping, with potential future directions for further technical development and clinical translation.

The CathPilot: Performance Validation and Preclinical Safety and Feasibility Assessment.

OBJECTIVES: Peripheral endovascular revascularization procedures often fail due to technical limitations of guidewire support, steering, and visualization. The novel CathPilot catheter aims to address these challenges. This study assesses the safety and feasibility of the CathPilot and compares its performance to conventional catheters for peripheral vascular interventions. METHODS: The study compared the CathPilot to non-steerable and steerable catheters. The success rates and access times for a relevant target inside a tortuous vessel phantom model were assessed. The reachable workspace within the vessel and the guidewire's force delivery capabilities were also evaluated. To validate the technology, chronic total occlusion tissue samples were used ex vivo to compare crossing success rates with conventional catheters. Finally, in vivo experiments in a porcine aorta were conducted to evaluate safety and feasibility. RESULTS: The success rates for reaching the set targets were 31%, 69%, and 100% with the non-steerable catheter, the steerable catheter, and the CathPilot, respectively. CathPilot had a significantly larger reachable workspace, and allowed for up to four times higher force delivery and pushability. In crossing of chronic total occlusion samples, the CathPilot achieved a success rate of 83% and 100%, for fresh and fixed lesions respectively, which was also significantly higher than conventional catheters. The device was fully functional in the in vivo study, and there were no signs of coagulation or damage to the vessel wall. CONCLUSION: This study shows the safety and feasibility of the CathPilot system and its potential to reduce failure and complication rates in peripheral vascular interventions. The novel catheter outperformed conventional catheters in all defined metrics. This technology can potentially improve the success rate and outcome of peripheral endovascular revascularization procedures.

Low Prevalence of Late Myocardial Injury on Cardiac MRI Following COVID-19 Infection.

BACKGROUND: The prevalence of abnormal cardiac magnetic resonance imaging (MRI) findings indicative of myocardial injury in patients who recovered from coronavirus disease 2019 (COVID-19) is currently unclear, with a high variability in the reported prevalence. PURPOSE: To assess the prevalence of myocardial injury after a COVID-19 infection. STUDY TYPE: Prospective, bicentric study. SUBJECTS: Seventy consecutive patients who recovered from COVID-19 and were previously hospitalized. Mean age was 57 years and 39% of the patients were female. Ten healthy controls and a comparator group of 75 nonischemic cardiomyopathy (NICM) patients were employed. FIELD STRENGTH/SEQUENCE: 1.5-T, steady-state free precession (SSFP) gradient-echo sequence, modified Look-Locker inversion recovery sequence with balanced SSFP readout, T2-prepared spiral readout sequence and a T1-weighted inversion recovery fast gradient-echo sequence was acquired ~4-5 months after recovery from COVID-19. ASSESSMENT: The SSFP sequence was utilized for the calculation of left and right ventricular volumes and ejection fractions (LVEF and RVEF) following manual endocardial contouring. T1 and T2 mapping was performed by pixel-wise exponential fitting, and T1 and T2 values were computed by manual contouring of the left ventricular endocardial and epicardial walls. Late gadolinium enhancement (LGE) images were graded qualitatively as LGE present or absent. STATISTICAL TESTS: T-tests and the χ2 or Fisher's exact tests were used to compare continuous and categorical variables respectively between the COVID-19 and NICM groups. Inter-rater agreement was evaluated by the intraclass correlation coefficient for continuous variables and Cohen's kappa test for LGE. RESULTS: Reduced RVEF occurred in 10%, LGE and elevated native T1 in 9%, reduced LVEF in 4%, and elevated T2 in 3% of COVID-19 patients, respectively. Patients with NICM had lower mean LVEF (41.6% ± 6% vs. 60% ± 7%), RVEF (46% ± 5% vs. 61% ± 9%), and a significantly higher prevalence of LGE (27% vs. 9%) when compared to those post-COVID-19. DATA CONCLUSION: Abnormal cardiac MRI findings may show a low prevalence in patients who recovered from COVID-19 and were previously hospitalized. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Experimental Protocol and Phantom Design and Development for Performance Characterization of Conventional Devices for Peripheral Vascular Interventions.

Conventional catheter-based interventions for treating peripheral artery disease suffer high failure and complication rates. The mechanical interactions with the anatomy constrain catheter controllability, while their length and flexibility limit their pushability. Also, the 2D X-ray fluoroscopy guiding these procedures fails to provide sufficient feedback about the device location relative to the anatomy. Our study aims to quantify the performance of conventional non-steerable (NS) and steerable (S) catheters in phantom and ex vivo experiments. In a 10 mm diameter, 30 cm long artery phantom model, with four operators, we evaluated the success rate and crossing time in accessing 1.25 mm target channels, the accessible workspace, and the force delivered through each catheter. For clinical relevance, we evaluated the success rate and crossing time in crossing ex vivo chronic total occlusions. For the S and NS catheters, respectively, users successfully accessed 69 and 31% of the targets, 68 and 45% of the cross-sectional area, and could deliver 14.2 and 10.2 g of mean force. Using a NS catheter, users crossed 0.0 and 9.5% of the fixed and fresh lesions, respectively. Overall, we quantified the limitations of conventional catheters (navigation, reachable workspace, and pushability) for peripheral interventions; this can serve as a basis for comparison with other devices.

A Deep Learning Segmentation Pipeline for Cardiac T1 Mapping Using MRI Relaxation-based Synthetic Contrast Augmentation.

Purpose: To design and evaluate an automated deep learning method for segmentation and analysis of cardiac MRI T1 maps with use of synthetic T1-weighted images for MRI relaxation-based contrast augmentation. Materials and Methods: This retrospective study included MRI scans acquired between 2016 and 2019 from 100 patients (mean age ± SD, 55 years ± 13; 72 men) across various clinical abnormalities with use of a modified Look-Locker inversion recovery, or MOLLI, sequence to quantify native T1 (T1native), postcontrast T1 (T1post), and extracellular volume (ECV). Data were divided into training (n = 60) and internal (n = 40) test subsets. "Synthetic" T1-weighted images were generated from the T1 exponential inversion-recovery signal model at a range of optimal inversion times, yielding high blood-myocardium contrast, and were used for contrast-based image augmentation during training and testing of a convolutional neural network for myocardial segmentation. Automated segmentation, T1, and ECV were compared with experts with use of Dice similarity coefficients (DSCs), correlation coefficients, and Bland-Altman analysis. An external test dataset (n = 147) was used to assess model generalization. Results: Internal testing showed high myocardial DSC relative to experts (0.81 ± 0.08), which was similar to interobserver DSC (0.81 ± 0.08). Automated segmental measurements strongly correlated with experts (T1native, R = 0.87; T1post, R = 0.91; ECV, R = 0.92), which were similar to interobserver correlation (T1native, R = 0.86; T1post, R = 0.94; ECV, R = 0.95). External testing showed strong DSC (0.80 ± 0.09) and T1native correlation (R = 0.88) between automatic and expert analysis. Conclusion: This deep learning method leveraging synthetic contrast augmentation may provide accurate automated T1 and ECV analysis for cardiac MRI data acquired across different abnormalities, centers, scanners, and T1 sequences.Keywords: MRI, Cardiac, Tissue Characterization, Segmentation, Convolutional Neural Network, Deep Learning Algorithms, Machine Learning Algorithms, Supervised Learning Supplemental material is available for this article. © RSNA, 2022.

Augmenting Performance: A Systematic Review of Optical See-Through Head-Mounted Displays in Surgery.

We conducted a systematic review of recent literature to understand the current challenges in the use of optical see-through head-mounted displays (OST-HMDs) for augmented reality (AR) assisted surgery. Using Google Scholar, 57 relevant articles from 1 January 2021 through 18 March 2022 were identified. Selected articles were then categorized based on a taxonomy that described the required components of an effective AR-based navigation system: data, processing, overlay, view, and validation. Our findings indicated a focus on orthopedic (n=20) and maxillofacial surgeries (n=8). For preoperative input data, computed tomography (CT) (n=34), and surface rendered models (n=39) were most commonly used to represent image information. Virtual content was commonly directly superimposed with the target site (n=47); this was achieved by surface tracking of fiducials (n=30), external tracking (n=16), or manual placement (n=11). Microsoft HoloLens devices (n=24 in 2021, n=7 in 2022) were the most frequently used OST-HMDs; gestures and/or voice (n=32) served as the preferred interaction paradigm. Though promising system accuracy in the order of 2-5 mm has been demonstrated in phantom models, several human factors and technical challenges-perception, ease of use, context, interaction, and occlusion-remain to be addressed prior to widespread adoption of OST-HMD led surgical navigation.

MRI-Guided Cardiac RF Ablation for Comparing MRI Characteristics of Acute Lesions and Associated Electrophysiologic Voltage Reductions.

OBJECTIVE: Radiofrequency (RF) energy delivered to cardiac tissue produces a core ablation lesion with surrounding edema, the latter of which has been implicated in acute procedural failure of Ventricular Tachycardia (VT) ablation and late arrhythmia recurrence. This study sought to investigate the electrophysiological characteristics of acute RF lesions in the left ventricle (LV) visualized with native-contrast Magnetic Resonance Imaging (MRI). METHODS: An MR-guided electrophysiology system was used to deliver RF ablation in the LV of 8 swine (9 RF lesions in total), then perform MRI and electroanatomic mapping. The permanent RF lesions and transient edema were delineated via native-contrast MRI segmentation of T1-weighted images and T2 maps respectively. Bipolar voltage measurements were matched with image characteristics of pixels adjacent to the catheter tip. Native-contrast MR visualization was verified with 3D late gadolinium enhanced MRI and histology. RESULTS: The T2-derived edema was significantly larger than the T1-derived RF lesion (2.1 ±1.5 mL compared to 0.58 ±0.34 mL; p=0.01). Bipolar voltage was significantly reduced in the presence of RF lesion core (p 0.05) and edema (p 0.05), with similar trends suggesting that both the permanent lesion and transient edema contributed to the region of reduced voltage. While bipolar voltage was significantly decreased where RF lesions are present (p 0.05), voltage did not change significantly with lesion transmurality (p 0.05). CONCLUSION: Permanent RF lesions and transient edema are distinct in native-contrast MR images, but not differentiable using bipolar voltage. SIGNIFICANCE: Intraprocedural native-contrast MRI may provide valuable lesion assessment in MR-guided ablation, whose clinical application is now feasible.

Oxygen saturation-dependent effects on blood transverse relaxation at low fields.

OBJECTIVE: Blood oxygenation can be measured using magnetic resonance using the paramagnetic effect of deoxy-haemoglobin, which decreases the [Formula: see text] relaxation time of blood. This [Formula: see text] contrast has been well characterised at the [Formula: see text] fields used in MRI (1.5 T and above). However, few studies have characterised this effect at lower magnetic fields. Here, the feasibility of blood oximetry at low field based on [Formula: see text] changes that are within a physiological relevant range is explored. This study could be used for specifying requirements for construction of a monitoring device based on low field permanent magnet systems. METHODS: A continuous flow circuit was used to control parameters such as oxygen saturation and temperature in a sample of blood. It flowed through a variable field magnet, where CPMG experiments were performed to measure its [Formula: see text]. In addition, the oxygen saturation was monitored by an optical sensor for comparison with the [Formula: see text] changes. RESULTS: These results show that at low [Formula: see text] fields, the change in blood [Formula: see text] due to oxygenation is small, but still detectable. The data measured at low fields are also in agreement with theoretical models for the oxy-deoxy [Formula: see text] effect. CONCLUSION: [Formula: see text] changes in blood due to oxygenation were observed at fields as low as 0.1 T. These results suggest that low field NMR relaxometry devices around 0.3 T could be designed to detect changes in blood oxygenation.

Myocardial blood flow is the dominant factor influencing cardiac magnetic resonance adenosine stress T2.

Stress imaging identifies ischemic myocardium by comparing hemodynamics during rest and hyperemic stress. Hyperemia affects multiple hemodynamic parameters in myocardium, including myocardial blood flow (MBF), myocardial blood volume (MBV), and venous blood oxygen levels (PvO2 ). Cardiac T2 is sensitive to these changes and therefore is a promising non-contrast option for stress imaging; however, the impact of individual hemodynamic factors on T2 is poorly understood, making the connection from altered T2 to changes within the tissue difficult. To better understand this interplay, we performed T2 mapping and measured various hemodynamic factors independently in healthy pigs at multiple levels of hyperemic stress, induced by different doses of adenosine (0.14-0.56 mg/kg/min). T1 mapping quantified changes in MBV. MBF was assessed with microspheres, and oxygen consumption was determined by the rate pressure product (RPP). Simulations were also run to better characterize individual contributions to T2. Myocardial T2, MBF, oxygen consumption, and MBV all changed to varying extents between each level of adenosine stress (T2 = 37.6-41.8 ms; MBF = 0.48-1.32 mL/min/g; RPP = 6507-4001 bmp*mmHg; maximum percent change in MBV = 1.31%). Multivariable analyses revealed MBF as the dominant influence on T2 during hyperemia (significant ß-values >7). Myocardial oxygen consumption had almost no effect on T2 (ß-values <0.002); since PvO2 is influenced by both oxygen consumption and MBF, PvO2 changes detected by T2 during adenosine stress can be attributed to MBF. Simulations varying PvO2 and MBV confirmed that PvO2 had the strongest influence on T2, but MBV became important at high PvO2 . Together, these data suggest a model where, during adenosine stress, myocardial T2 responds predominantly to changes in MBF, but at high hyperemia MBV is also influential. Thus, changes in adenosine stress T2 can now be interpreted in terms of the physiological changes that led to it, enabling T2 mapping to become a viable non-contrast option to detect ischemic myocardial tissue.

Suspected subclinical myocarditis detected by cardiac magnetic resonance imaging late post COVID-19 recovery.

There is growing evidence of the potential for cardiac involvement in patients who have been infected with COVID-19. In this case study, we present a patient with no history of cardiovascular disease, who was hospitalized for COVID-19 pneumonia and subsequently recovered. Despite normal serum troponin levels and left ventricular structure and function, multi-parametric cardiac magnetic resonance imaging revealed a classic myocarditis-like pattern of injury approximately 6 months after his convalescence. Physicians should be aware of the possibility of late myocardial injury/inflammation in patients with recovered COVID-19, even in the absence of elevated troponin levels and/or left ventricular dysfunction. .

T2-based area-at-risk and edema are influenced by ischemic duration in acute myocardial infarction.

The purpose of our study was to assess whether T2 MRI identifies the infarcted myocardium or the true area-at-risk (AAR) and whether edema is present in the salvageable region following acute myocardial infarction (MI). The study involved a porcine model of MI with a coronary occlusion model of either 60 min or 90 min. Imaging was performed on a 3T MRI pre-occlusion and at day 3 post-MI. Prior-MI, myocardial perfusion territory (MPT) maps were obtained under MRI via direct intracoronary injection of contrast agent. Post-MI, edema extent was quantified by T2 mapping while infarction and microvascular obstruction (MVO) were assessed by late gadolinium enhancement (LGE). Anatomically registered short-axis slices were analyzed for MPT, T2-AAR and infarct areas and T2 relaxation values. Animals were divided into groups with (MVO+) and without MVO (MVO-). T2-AAR area was significantly greater than infarct area in both groups. In the MVO+ group, T2-AAR and MPT were comparable and highly correlated, whereas, in the MVO- group, T2-AAR significantly underestimated MPT without any trend. T2 values in the salvageable myocardium were found to be significantly higher than those in remote myocardium. Our methodology offers the advantage that all images are acquired within the same MRI reference as opposed to complex co-registration with gross pathology. Our study suggests that edema may expand beyond the infarct zone over the entire ischemic bed. T2-AAR may be more clinically relevant than true AAR by perfusion territory since it identifies the "salvageable" myocardium.

Technical Note: Fully automatic segmental relaxometry (FASTR) for cardiac magnetic resonance T1 mapping.

PURPOSE: Cardiac relaxometry techniques, particularly T1 mapping, have recently gained clinical importance in various cardiac pathologies. Myocardial T1 and extracellular volume are usually calculated from manual identification of left ventricular epicardial and endocardial regions. This is a laborious process, particularly for large volume studies. Here we present a fully automated relaxometry framework (FASTR) for segmental analysis of T1 maps (both native and postcontrast) and partition coefficient (λ). METHODS: Patients (N = 11) were imaged postacute myocardial infarction on a 1.5T clinical scanner. The scan protocol involved CINE-SSFP imaging, native, and post-contrast T1 mapping using the Modified Look-Locker Inversion (MOLLI) recovery sequence. FASTR consisted of automatic myocardial segmentation of spatio-temporally coregistered CINE images as an initial guess, followed by refinement of the contours on the T1 maps to derive segmental T1 and λ. T1 and λ were then compared to those obtained from two trained expert observers. RESULTS: Robust endocardial and epicardial contours were achieved on T1 maps despite the presence of infarcted tissue. Relative to experts, FASTR resulted in myocardial Dice coefficients (native T1: 0.752 ± 0.041; postcontrast T1: 0.751 ± 0.057) that were comparable to interobserver Dice (native T1: 0.803 ± 0.045; postcontrast T1: 0.799 ± 0.054). There were strong correlations observed for T1 and λ derived from experts and FASTR (native T1: r = 0.83; postcontrast T1: r = 0.87; λ: r = 0.78; P < 0.0001), which were comparable to inter-expert correlation coefficients (native T1: r = 0.90; postcontrast T1: r = 0.93; λ: r = 0.80; P < 0.0001). CONCLUSIONS: Our fully automated framework, FASTR, can generate accurate myocardial segmentations for native and postcontrast MOLLI T1 analysis without the need for manual intervention. Such a design is appealing for high volume clinical protocols.

A calcified chronic total occlusion preclinical model.

OBJECTIVE: To create an experimental chronic total occlusion (CTO) model with calcification by dietary modification (cholesterol, calcium carbonate, vitamin D) and local injection of pro-calcification factors (dipotassium phosphate, calcium chloride, and bone morphogenetic protein-2 [BMP-2]). BACKGROUND: Percutaneous revascularization of CTOs frequently fails in heavily calcified occlusions. Development of novel approaches requires a reproducible preclinical model of calcified CTO. METHODS: CTOs were created in 18 femoral arteries of 9 New Zealand White rabbits using the thrombin injection model. Dietary interventions included a high cholesterol diet (0.5% or 0.25%), calcium carbonate (150 mg × 3-5 days/week), and vitamin D (50,000 U × 3-5 days/week). In selected animals, BMP-2 (1-4 µg), dipotassium phosphate, and calcium chloride were injected locally at the time of CTO creation. Animals were sacrificed at 2 weeks (n = 4 arteries), 6 weeks (n = 4 arteries), and 10-12 weeks (n = 14 arteries). RESULTS: CTOs showed evidence of chronic lipid feeding (foam cells) and chronic inflammation (intimal/medial fibrosis and microvessels, inflammatory cells, internal elastic lamina disruption). In calcium/vitamin D supplemented rabbits, mineralization (calcification and/or ossification) was evident as early as 2 weeks post CTO creation, and in 78% of the overall arteries. Mineralization changes were not present in the absence of calcium/vitamin D dietary supplements. Mineralization occurred in 85% of BMP-treated arteries and 60% of arteries without BMP. CONCLUSIONS: Complex mineralization occurs in preclinical CTO models with dietary supplementation of cholesterol with vitamin D and calcium.

Hemorrhage promotes chronic adverse remodeling in acute myocardial infarction: a T1 , T2 and BOLD study.

Hemorrhage is recognized as a new independent predictor of adverse outcomes following acute myocardial infarction. However, the mechanisms of its effects are less understood. The aim of our study was to probe the downstream impact of hemorrhage towards chronic remodeling, including inflammation, vasodilator function and matrix alterations in an experimental model of hemorrhage. Myocardial hemorrhage was induced in the porcine heart by intracoronary injection of collagenase. Animals (N = 18) were subjected to coronary occlusion followed by reperfusion in three groups (six/group): 8 min ischemia with hemorrhage (+HEM), 45 min infarction with no hemorrhage (I - HEM) and 45 min infarction with hemorrhage (I + HEM). MRI was performed up to 4 weeks after intervention. Cardiac function, edema (T2 , T1 ), hemorrhage (T2 *), vasodilator function (T2 BOLD), infarction and microvascular obstruction (MVO) and partition coefficient (pre- and post-contrast T1 ) were computed. Hemorrhage was induced only in the +HEM and I + HEM groups on Day 1 (low T2 * values). Infarct size was the greatest in the I + HEM group, while the +HEM group showed no observable infarct. MVO was seen only in the I + HEM group, with a 40% occurrence rate. Function was compromised and ventricular volume was enlarged only in the hemorrhage groups and not in the ischemia-alone group. In the infarct zone, edema and matrix expansion were the greatest in the I + HEM group. In the remote myocardium, T2 elevation and matrix expansion associated with a transient vasodilator dysfunction were observed in the hemorrhage groups but not in the ischemia-alone group. Our study demonstrates that the introduction of myocardial hemorrhage at reperfusion results in greater myocardial damage, upregulated inflammation, chronic adverse remodeling and remote myocardial alterations beyond the effects of the initial ischemic insult. A systematic understanding of the consequences of hemorrhage will potentially aid in the identification of novel therapeutics for high-risk patients progressing towards heart failure.

Action of iron chelator on intramyocardial hemorrhage and cardiac remodeling following acute myocardial infarction.

Intramyocardial hemorrhage is an independent predictor of adverse outcomes in ST-segment elevation myocardial infarction (STEMI). Iron deposition resulting from ischemia-reperfusion injury (I/R) is pro-inflammatory and has been associated with adverse remodeling. The role of iron chelation in hemorrhagic acute myocardial infarction (AMI) has never been explored. The purpose of this study was to investigate the cardioprotection offered by the iron-chelating agent deferiprone (DFP) in a porcine AMI model by evaluating hemorrhage neutralization and subsequent cardiac remodeling. Two groups of animals underwent a reperfused AMI procedure: control and DFP treated (N = 7 each). A comprehensive MRI examination was performed in healthy state and up to week 4 post-AMI, followed by histological assessment. Infarct size was not significantly different between the two groups; however, the DFP group demonstrated earlier resolution of hemorrhage (by T2* imaging) and edema (by T2 imaging). Additionally, ventricular enlargement and myocardial hypertrophy (wall thickness and mass) were significantly smaller with DFP, suggesting reduced adverse remodeling, compared to control. The histologic results were consistent with the MRI findings. To date, there is no effective targeted therapy for reperfusion hemorrhage. Our proof-of-concept study is the first to identify hemorrhage-derived iron as a therapeutic target in I/R and exploit the cardioprotective properties of an iron-chelating drug candidate in the setting of AMI. Iron chelation could potentially serve as an adjunctive therapy in hemorrhagic AMI.

Multi-contrast volumetric imaging with isotropic resolution for assessing infarct heterogeneity: Initial clinical experience.

BACKGROUND: To evaluate accelerated multi-contrast volumetric imaging with isotropic resolution reconstructed using low-rank and spatially varying edge-preserving constrained compressed sensing parallel imaging reconstruction (CP-LASER), for assessing infarct heterogeneity on post-infarction patients as a precursor to studies of utility for predicting ventricular arrhythmias. METHODS: Eleven patients with prior myocardial infarction were included in the study. All subjects underwent cardiovascular magnetic resonance (CMR) scans including conventional two-dimensional late gadolinium enhancement (2D LGE) and three-dimensional multi-contrast late enhancement (3D MCLE) post-contrast. The extent of the infarct core and peri-infarct gray zone of a limited mid-ventricular slab were derived respectively by analyzing MCLE images with an isotropic resolution of 2.2 mm and an anisotropic resolution of 2.2×2.2×8.8 mm 3 , and LGE images with a resolution of 1.37×2.7×8 mm 3 ; the respective measures across all subjects were statistically compared. RESULTS: Using 3D MCLE, the infarct core size measured with isotropic resolution was similar to that measured with anisotropic resolution, while the peri-infarct gray zone size measured with isotropic resolution was smaller than that measured with anisotropic resolution ( p<0.001 , Cohen's dz=1.33 ). Isotropic 3D MCLE yielded a significantly smaller measure of the peri-infarct gray zone size than conventional 2D LGE ( p=0.0016 , Cohen's dz=1.20 ). Overall, we have successfully shown the utility of isotropic 3D MCLE in a pilot patient study. Our results suggest that smaller voxels lead to more accurate differentiation between isotropic 3D MCLE-derived gray zone and core infarct because of diminished partial volume effect. CONCLUSION: The CP-LASER accelerated 3D MCLE with isotropic resolution can be used in patients and yields excellent delineation of infarct and peri-infarct gray zone characteristics.

Evaluating a novel free-breathing accelerated cardiac MRI cine sequence in patients with cardiomyopathy.

INTRODUCTION: Cardiac magnetic resonance imaging (CMR) is the gold standard for the assessment of left ventricular (LV) function. However, traditional sequences are time-consuming and require breath-holding. Our aim was to evaluate the image quality of LV functional assessment with a novel, accelerated, free-breathing cine sequence and to compare LV functional parameters between it and a traditional sequence. METHODS: This was a prospective cohort study of 31 patients with cardiomyopathy. All studies were performed on a 1.5 Tesla scanner. LV function was first determined using contiguous short axis slices covering the left ventricle from the base to the apex acquired with the standard cine sequence. Next, the accelerated sequence was acquired for each patient. The Wilcoxon Matched-Pair Sign Rank Test was used to compare image quality between the accelerated and traditional cine imaging sequences. Standard and accelerated left ventricular volumes and ejection fraction were compared using linear regression. Bland-Altman plots were then constructed to evaluate agreement, interobserver and intraobserver variability for left ventricular volumes and ejection fraction. RESULTS: Mean acquisition time was 29 s for the accelerated sequence vs. 410 s for the traditional sequence. Qualitative assessment of image quality was similar for both sequences (p = 0.23). There were no significant differences in terms of LVEDV, LVESV, LVSV, LV mass and LVEF when calculated from either sequence with very good agreement between the standard and accelerated sequences. The mean differences with 95% limits of agreement were as follows: LV mass (-0.6, -22.9 g, 21.6 g), LVEDV (5.1 mL, -18.4 mL, 28.9 mL), LVEF (-0.3, -5.4, 4.7), LVESV (4.0 mL, -12.0 mL, 20.0 mL), LVSV (1.1 mL, -13.3 mL, 15.5 mL). Interobserver variability ranged from 0.1 to 6.3% while intraobserver variability ranged from 0.1 to 1.8%. CONCLUSIONS: The accelerated free-breathing cine sequence performed similarly to standard of care multi breath-hold cine imaging and was acquired in a fraction of the time without the need for breath-holding. If applied to clinical practice, this sequence can significantly reduce scanning time and facilitate CMR scanning in those patients who are unable to breath-hold.