Using diffusion tensor imaging to depict myocardial changes after matured pluripotent stem cell-derived cardiomyocyte transplantation.

BACKGROUND: Novel treatment strategies are needed to improve the structure and function of the myocardium post-infarction. In vitro-matured pluripotent stem cell-derived cardiomyocytes (PSC-CMs) have been shown to be a promising regenerative strategy. We hypothesized that mature PSC-CMs will have anisotropic structure and improved cell alignment when compared to immature PSC-CMs using cardiovascular magnetic resonance (CMR) in a guinea pig model of cardiac injury. METHODS: Guinea pigs (n = 16) were cryoinjured on day -10, followed by transplantation of either 108 polydimethylsiloxane (PDMS)-matured PSC-CMs (n = 6) or 108 immature tissue culture plastic (TCP)-generated PSC-CMs (n = 6) on day 0. Vehicle (sham-treated) subjects were injected with a pro-survival cocktail devoid of cells (n = 4), while healthy controls (n = 4) did not undergo cryoinjury or treatment. Animals were sacrificed on either day +14 or day +28 post-transplantation. Animals were imaged ex vivo on a 7T Bruker MRI. A 3D diffusion tensor imaging (DTI) sequence was used to quantify structure via fractional anisotropy (FA), mean diffusivity (MD), and myocyte alignment measured by the standard deviation of the transverse angle (TA). RESULTS: MD and FA of mature PDMS grafts demonstrated anisotropy was not significantly different than the healthy control hearts (MD = 1.1 ± 0.12 × 10-3 mm2/s vs 0.93 ± 0.01 × 10-3 mm2/s, p = 0.4 and FA = 0.22 ± 0.05 vs 0.26 ± 0.001, p = 0.5). Immature TCP grafts exhibited significantly higher MD than the healthy control (1.3 ± 0.08 × 10-3 mm2/s, p < 0.05) and significantly lower FA than the control (0.12 ± 0.02, p < 0.05) but were not different from mature PDMS grafts in this small cohort. TA of healthy controls showed low variability and was not significantly different than mature PDMS grafts (p = 0.4) while immature TCP grafts were significantly different (p < 0.001). DTI parameters of mature graft tissue trended toward that of the healthy myocardium, indicating the grafted cardiomyocytes may have a similar phenotype to healthy tissue. Contrast-enhanced magnetic resonance images corresponded well to histological staining, demonstrating a non-invasive method of localizing the repopulated cardiomyocytes within the scar. CONCLUSIONS: The DTI measures within graft tissue were indicative of anisotropic structure and showed greater myocyte organization compared to the scarred territory. These findings show that MRI is a valuable tool to assess the structural impacts of regenerative therapies.

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.

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.

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.

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.

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.

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.

Left ventricular strain analysis using cardiac magnetic resonance imaging in patients undergoing in-centre nocturnal haemodialysis.

AIM: Intensified haemodialysis is associated with regression of left ventricular (LV) mass. Compared to LV ejection fraction, LV strain allows more direct assessment of LV function. We sought to assess the impact of in-centre nocturnal haemodialysis (INHD) on global LV strain (radial, circumferential, and longitudinal) and torsion by cardiac MRI (CMR). METHODS: In this prospective, two-centre cohort study, 37 participants on conventional haemodialysis (CHD, 3-4 h/session for three sessions/week) converted to INHD (7-8 h/session for three sessions/week) and 30 participants continued CHD. Participants underwent CMR using a standardized protocol and had biomarker measurements at baseline and 52 weeks. RESULTS: Among the 55 participants (mean age 55; 40% women) with complete CMR data, those who converted to INHD had a significant improvement in their global circumferential strain (GCS, P = 0.025), while those continuing CHD did not have any significant changes in LV strain. When the two groups were compared, there was significant improvement in torsion. LV strains were significantly correlated with each other, but not with troponin I, C-reactive protein, or brain natriuretic protein (NT-proBNP), except for global longitudinal strain (GLS) with troponin I (P = 0.001) and NT-proBNP (P = 0.038). CONCLUSION: Conversion to INHD was associated with significant improvement in GCS over one year of study, although comparisons with the CHD group were not significant. There was also a significant decrease in torsion in the INHD group compared with CHD. Improvement in LV regional function would support the notion that INHD has favourable effects on both LV structure and function.

Accelerated multicontrast volumetric imaging with isotropic resolution for improved peri-infarct characterization using parallel imaging, low-rank and spatially varying edge-preserving sparse modeling.

PURPOSE: To achieve consistent effectiveness in reconstruction of fine image features for cases of varying contrast-to-noise ratio (CNR) to facilitate translating accelerated multicontrast volumetric imaging with isotropic resolution toward clinical utility in peri-infarct characterization. THEORY AND METHODS: A low-rank and spatially varying edge-preserving constrained compressed sensing parallel imaging reconstruction method (CP-LASER) is developed to effectively preserve contrast of small-scale structures for highly accelerated multicontrast volumetric imaging in CNR-limited scenarios. CP-LASER synergistically integrates parallel imaging, low-rank and spatially varying edge-preserving sparse modeling to achieve high signal-to-noise-ratio efficiency by leveraging prior knowledge about signal properties including coil sensitivity weighting, spatiotemporally correlated signal relaxation, and spatially varying sparsity. RESULTS: In the preclinical study using highly accelerated multicontrast volumetric imaging with an isotropic 1.5-mm resolution, CP-LASER demonstrated robust multicontrast reconstruction of peri-infarct characteristics with excellent correspondence with histopathology. CP-LASER provides better delineation of the peri-infarct border zone with improved sharpness than alternative methods in a clinical demonstration on 1.5T with an isotropic 2.2-mm resolution achieved in a single breath-hold. CONCLUSION: Accelerated multicontrast volumetric imaging with isotropic resolution using CP-LASER has demonstrated the potential to improve peri-infarct characterization in a clinical setting. Magn Reson Med 79:3018-3031, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Toward in vivo quantification of induced RF currents on long thin conductors.

PURPOSE: Most MR-guided catheter-based procedures, and imaging of patients with implanted medical devices, are currently contraindicated due to a significant risk of heating associated with induced RF currents. The induced RF current produces a corresponding artifact which can be used to remotely characterize current and safely predict RF heating. Application of this remote technique in vivo to safely quantify RF heating risk may allow for execution of many scans currently contraindicated. Sources of phase other than induced RF current may present difficulty in practical in vivo. METHODS: A custom ultra-short echo time (UTE) sequence was developed to minimize unwanted phase contributions. A phantom experiment was performed to compare current characterization using a stock gradient-echo (GRE) sequence and the custom UTE sequence following calibration of the temperature measurement apparatus using a previously published heating prediction technique. Animal experiments were used to investigate the feasibility of using the UTE sequence to quantify RF heating. RESULTS: Current characterization and heating prediction with a stock GRE sequence was equivalent to that with the custom UTE sequence. Heating measurements and image-based predictions in animal experiments agreed within error in all experiments. CONCLUSION: Through comparison of measured heating and image-based prediction, feasibility of using a custom UTE sequence to quantify RF heating risk in vivo was demonstrated.

Magnetic resonance imaging characteristics of lesions relate to the difficulty of peripheral arterial endovascular procedures.

OBJECTIVE: Limitations with current peripheral arterial imaging modalities make selection of patients for percutaneous vascular interventions difficult. The purpose of this study was to determine whether a novel preprocedural magnetic resonance imaging (MRI) method can identify lesions that would be more challenging to cross during percutaneous vascular intervention. METHODS: Fourteen patients with peripheral arterial disease underwent MRI before their intervention. A novel steady-state free precession flow-independent magnetic resonance (MR) angiogram was used to locate lesions, and an ultrashort echo time image was used to characterize hard lesion components including calcium and dense collagen. Lesions were characterized as hard if ≥50% of the lumen was occluded with calcium or collagen (as determined by MR image characteristics) in the hardest cross section within the lesion. The primary outcome was the time it took to cross a guidewire through the target lesion. The secondary outcome was the need for stenting. RESULTS: Of 14 lesions, 8 (57%) were defined as hard and 6 (43%) were soft on the basis of MR image characteristics. Hard lesions took significantly longer to cross than soft lesions (average, 14 minutes 49 seconds vs 2 minutes 17 seconds; P = .003). Hard lesions also required stenting more often than soft lesions (Fisher exact test, P = .008). Of 14 lesions, 2 (14%) could not be crossed with a guidewire, and both lesions were hard. MR images also detected occult patencies and noncalcified hard lesions that could not be seen on X-ray angiography. CONCLUSIONS: MRI can be used to determine which peripheral arterial lesions are more difficult to cross with a guidewire. Future work will determine whether MRI lesion characterization can predict long-term endovascular outcomes to aid in procedure planning.

Perfusion measures for symptom severity and differential outcome of revascularization in limb ischemia: Preliminary results with arterial spin labeling reactive hyperemia.

BACKGROUND: Previously, a theoretical model based on microvascular physiology was established to facilitate the interpretation of calf perfusion dynamics recorded by arterial spin labeling (ASL). PURPOSE: To investigate the clinical relevance of novel perfusion indices by comparing them to the symptoms, response to revascularization, and short-term functional outcome in patients with peripheral arterial disease (PAD). STUDY TYPE: Prospective cohort study. POPULATION: Nineteen patients with PAD. FIELD STRENGTH/SEQUENCE: Pulsed ASL at 3T. ASSESSMENT: The mid-calf reactive hyperemia induced by 2 minutes of arterial occlusion was recorded in PAD patients. The perfusion responses were characterized by the peak, time-to-peak, and physiological model-derived indices including the baseline perfusion fr , arterial resistance Ra , and compliance Ca , and sensitivity gATP and response time τATP of downstream microvasculature to metabolic stress. These indices were compared to the disease severity and outcome within 6 months after revascularization assessed by self-reported symptoms and the ankle-brachial index. Disease severity was categorized as asymptomatic, claudication, or critical limb ischemia. The outcome was categorized as symptom resolved or limited improvement. STATISTICAL TESTS: Severity and outcome groups were compared using Mann-Whitney and Kruskal-Wallis tests with Holm-Sidak adjustments. RESULTS: The peak perfusion decreased and model arterial resistance increased progressively with increasing severity of limb ischemia (P = 0.0402 and 0.0413, respectively). Eleven patients had a successful endovascular procedure, including six patients who had symptoms resolved, four patients who had remaining leg pain, and one patient lost to follow-up. The subjects with limited improvement had significantly lower preintervention microvascular sensitivity gATP than those with symptoms resolved (8.72 ± 1.46 vs. 4.93 ± 0.91, P = 0.0466). DATA CONCLUSION: ASL reactive hyperemia reflects multiple aspects of the pathophysiology. Measures of macrovascular arterial disease are related to the manifested symptom severity, whereas preintervention gATP associated with microvascular dysfunction is related to prognosis following revascularization. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2018;47:1578-1588.

Hyperpolarized 13C Metabolic MRI of the Human Heart: Initial Experience.

RATIONALE: Altered cardiac energetics is known to play an important role in the progression toward heart failure. A noninvasive method for imaging metabolic markers that could be used in longitudinal studies would be useful for understanding therapeutic approaches that target metabolism. OBJECTIVE: To demonstrate the first hyperpolarized 13C metabolic magnetic resonance imaging of the human heart. METHODS AND RESULTS: Four healthy subjects underwent conventional proton cardiac magnetic resonance imaging followed by 13C imaging and spectroscopic acquisition immediately after intravenous administration of a 0.1 mmol/kg dose of hyperpolarized [1-13C]pyruvate. All subjects tolerated the procedure well with no adverse effects reported ≤1 month post procedure. The [1-13C]pyruvate signal appeared within the chambers but not within the muscle. Imaging of the downstream metabolites showed 13C-bicarbonate signal mainly confined to the left ventricular myocardium, whereas the [1-13C]lactate signal appeared both within the chambers and in the myocardium. The mean 13C image signal:noise ratio was 115 for [1-13C]pyruvate, 56 for 13C-bicarbonate, and 53 for [1-13C]lactate. CONCLUSIONS: These results represent the first 13C images of the human heart. The appearance of 13C-bicarbonate signal after administration of hyperpolarized [1-13C]pyruvate was readily detected in this healthy cohort (n=4). This shows that assessment of pyruvate metabolism in vivo in humans is feasible using current technology. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02648009.

Non-contrast assessment of microvascular integrity using arterial spin labeled cardiovascular magnetic resonance in a porcine model of acute myocardial infarction.

BACKGROUND: Following acute myocardial infarction (AMI), microvascular integrity and function may be compromised as a result of microvascular obstruction (MVO) and vasodilator dysfunction. It has been observed that both infarcted and remote myocardial territories may exhibit impaired myocardial blood flow (MBF) patterns associated with an abnormal vasodilator response. Arterial spin labeled (ASL) CMR is a novel non-contrast technique that can quantitatively measure MBF. This study investigates the feasibility of ASL-CMR to assess MVO and vasodilator response in swine. METHODS: Thirty-one swine were included in this study. Resting ASL-CMR was performed on 24 healthy swine (baseline group). A subset of 13 swine from the baseline group underwent stress ASL-CMR to assess vasodilator response. Fifteen swine were subjected to a 90-min left anterior descending (LAD) coronary artery occlusion followed by reperfusion. Resting ASL-CMR was performed post-AMI at 1-2 days (N = 9, of which 6 were from the baseline group), 1-2 weeks (N = 8, of which 4 were from the day 1-2 group), and 4 weeks (N = 4, of which 2 were from the week 1-2 group). Resting first-pass CMR and late gadolinium enhancement (LGE) were performed post-AMI for reference. RESULTS: At rest, regional MBF and physiological noise measured from ASL-CMR were 1.08 ± 0.62 and 0.15 ± 0.10 ml/g/min, respectively. Regional MBF increased to 1.47 ± 0.62 ml/g/min with dipyridamole vasodilation (P < 0.001). Significant reduction in MBF was found in the infarcted region 1-2 days, 1-2 weeks, and 4 weeks post-AMI compared to baseline (P < 0.03). This was consistent with perfusion deficit seen on first-pass CMR and with MVO seen on LGE. There were no significant differences between measured MBF in the remote regions pre and post-AMI (P > 0.60). CONCLUSIONS: ASL-CMR can assess vasodilator response in healthy swine and detect significant reduction in regional MBF at rest following AMI. ASL-CMR is an alternative to gadolinium-based techniques for assessment of MVO and microvascular integrity within infarcted, as well as salvageable and remote myocardium. This has the potential to provide early indications of adverse remodeling processes post-ischemia.

Cardiovascular magnetic resonance guided ablation and intra-procedural visualization of evolving radiofrequency lesions in the left ventricle.

BACKGROUND: Radiofrequency (RF) ablation has become a mainstay of treatment for ventricular tachycardia, yet adequate lesion formation remains challenging. This study aims to comprehensively describe the composition and evolution of acute left ventricular (LV) lesions using native-contrast cardiovascular magnetic resonance (CMR) during CMR-guided ablation procedures. METHODS: RF ablation was performed using an actively-tracked CMR-enabled catheter guided into the LV of 12 healthy swine to create 14 RF ablation lesions. T2 maps were acquired immediately post-ablation to visualize myocardial edema at the ablation sites and T1-weighted inversion recovery prepared balanced steady-state free precession (IR-SSFP) imaging was used to visualize the lesions. These sequences were repeated concurrently to assess the physiological response following ablation for up to approximately 3 h. Multi-contrast late enhancement (MCLE) imaging was performed to confirm the final pattern of ablation, which was then validated using gross pathology and histology. RESULTS: Edema at the ablation site was detected in T2 maps acquired as early as 3 min post-ablation. Acute T2-derived edematous regions consistently encompassed the T1-derived lesions, and expanded significantly throughout the 3-h period post-ablation to 1.7 ± 0.2 times their baseline volumes (mean ± SE, estimated using a linear mixed model determined from n = 13 lesions). T1-derived lesions remained approximately stable in volume throughout the same time frame, decreasing to 0.9 ± 0.1 times the baseline volume (mean ± SE, estimated using a linear mixed model, n = 9 lesions). CONCLUSIONS: Combining native T1- and T2-based imaging showed that distinctive regions of ablation injury are reflected by these contrast mechanisms, and these regions evolve separately throughout the time period of an intervention. An integrated description of the T1-derived lesion and T2-derived edema provides a detailed picture of acute lesion composition that would be most clinically useful during an ablation case.

MRI for peripheral artery disease: Introductory physics for vascular physicians.

Magnetic resonance imaging (MRI) has advanced significantly in the past decade and provides a safe and non-invasive method of evaluating peripheral artery disease (PAD), with and without using exogenous contrast agents. MRI offers a promising alternative for imaging patients but the complexity of MRI can make it less accessible for physicians to understand or use. This article provides a brief introduction to the technical principles of MRI for physicians who manage PAD patients. We discuss the basic principles of how MRI works and tailor the discussion to how MRI can evaluate anatomic characteristics of peripheral arterial lesions.

Multicontrast reconstruction using compressed sensing with low rank and spatially varying edge-preserving constraints for high-resolution MR characterization of myocardial infarction.

PURPOSE: To enable robust reconstruction for highly accelerated three-dimensional multicontrast late enhancement imaging to provide improved MR characterization of myocardial infarction with isotropic high spatial resolution. THEORY AND METHODS: A new method using compressed sensing with low rank and spatially varying edge-preserving constraints (CS-LASER) is proposed to improve the reconstruction of fine image details from highly undersampled data. CS-LASER leverages the low rank feature of the multicontrast volume series in MR relaxation and integrates spatially varying edge preservation into the explicit low rank constrained compressed sensing framework using weighted total variation. With an orthogonal temporal basis pre-estimated, a multiscale iterative reconstruction framework is proposed to enable the practice of CS-LASER with spatially varying weights of appropriate accuracy. RESULTS: In in vivo pig studies with both retrospective and prospective undersamplings, CS-LASER preserved fine image details better and presented tissue characteristics with a higher degree of consistency with histopathology, particularly in the peri-infarct region, than an alternative technique for different acceleration rates. An isotropic resolution of 1.5 mm was achieved in vivo within a single breath-hold using the proposed techniques. CONCLUSION: Accelerated three-dimensional multicontrast late enhancement with CS-LASER can achieve improved MR characterization of myocardial infarction with high spatial resolution. Magn Reson Med 78:598-610, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Real-time MRI guidance of cardiac interventions.

Cardiac magnetic resonance imaging (MRI) is appealing to guide complex cardiac procedures because it is ionizing radiation-free and offers flexible soft-tissue contrast. Interventional cardiac MR promises to improve existing procedures and enable new ones for complex arrhythmias, as well as congenital and structural heart disease. Guiding invasive procedures demands faster image acquisition, reconstruction and analysis, as well as intuitive intraprocedural display of imaging data. Standard cardiac MR techniques such as 3D anatomical imaging, cardiac function and flow, parameter mapping, and late-gadolinium enhancement can be used to gather valuable clinical data at various procedural stages. Rapid intraprocedural image analysis can extract and highlight critical information about interventional targets and outcomes. In some cases, real-time interactive imaging is used to provide a continuous stream of images displayed to interventionalists for dynamic device navigation. Alternatively, devices are navigated relative to a roadmap of major cardiac structures generated through fast segmentation and registration. Interventional devices can be visualized and tracked throughout a procedure with specialized imaging methods. In a clinical setting, advanced imaging must be integrated with other clinical tools and patient data. In order to perform these complex procedures, interventional cardiac MR relies on customized equipment, such as interactive imaging environments, in-room image display, audio communication, hemodynamic monitoring and recording systems, and electroanatomical mapping and ablation systems. Operating in this sophisticated environment requires coordination and planning. This review provides an overview of the imaging technology used in MRI-guided cardiac interventions. Specifically, this review outlines clinical targets, standard image acquisition and analysis tools, and the integration of these tools into clinical workflow. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2017;46:935-950.

Puncturing Plaques.

PURPOSE: To test and validate magnetic resonance imaging (MRI) sequences for peripheral artery lesion characterization and relate the MRI characteristics to the amount of force required for a guidewire to puncture peripheral chronic total occlusions (CTOs) as a surrogate for immediate failure of endovascular therapy. METHODS: Diseased superficial femoral, popliteal, and tibial artery segments containing 55 atherosclerotic lesions were excised from the amputated limbs of 7 patients with critical limb ischemia. The lesions were imaged at high resolution (75 µm3 voxels) with T2-weighted (T2W) and ultrashort echo time (UTE) sequences on a 7-T MR scanner. The MR images (n=15) were validated with micro-computed tomography and histology. CTOs (n=40) were classified by their MR signal characteristics as "soft" (signals indicating fat, thrombus, microchannels, or loose fibrous tissue), "hard" (collagen and/or speckled calcium signals), or "calcified" (calcified nodule signals). A 2-kg load cell advanced the back end of a 0.035-inch stiff guidewire at a fixed displacement rate (0.05 mm/s) through the CTOs, and the forces required to cross each lesion were measured. RESULTS: T2W images showed fat as hyperintense and hardened tissue as hypointense. Calcium and thrombus appeared as a signal void in conventional MRI sequences but were easily identified in UTE images (thrombus was hyperintense and calcium hypointense). MRI accurately differentiated "hard," "soft," and "calcified" CTOs based on associated guidewire puncture force. The guidewire could not enter "calcified" CTOs (n=6) at all. "Hard" CTOs (n=9) required a significantly higher (p<0.001) puncture force of 1.71±0.51 N vs 0.43±0.36 N for "soft" CTOs (n=25). CONCLUSION: MRI characteristics of PAD lesions correlate with guidewire puncture forces, an important aspect of crossability. Future work will determine if clinical MR scanners can be used to predict success in peripheral vascular interventions.