Avinash Kali

Detection of acute reperfusion myocardial hemorrhage with cardiac MR imaging: T2 versus T2.

PURPOSE To evaluate T2 and T2* changes in acute reperfused hemorrhagic and nonhemorrhagic myocardial infarctions and to determine which technique is more suitable in the detection of intramyocardial hemorrhage at 1.5 T. MATERIALS AND METHODS Patient studies were approved by the institutional review board and were HIPAA compliant. Patients (n = 14, three women) with first ST-elevation myocardial infarction underwent cardiac magnetic resonance (MR) imaging 3 days after angioplasty. T2* maps, T2 short inversion time inversion-recovery (STIR) images, and late gadolinium enhancement (LGE) images were acquired. Animal studies were approved by the institutional animal care and use committee. Canines (n = 20) were subjected to ischemia-reperfusion injury, and cardiac MR imaging was performed 5 days after reperfusion. T2* and T2 maps and T2 STIR and LGE images were acquired. Repeated-measures analysis of variance or the Friedman test was used to compare T2 and T2* changes in patients with hemorrhagic infarctions and those with nonhemorrhagic infarctions. RESULTS Relative to remote myocardium, mean T2* of hemorrhagic infarctions was 54% ± 13 (standard deviation) lower in patients (15.9 msec ± 4.5 vs 35.2 msec ± 2.1, P < .001) and 40% ± 10 lower in canines (23.0 msec ± 4.0 vs 39.3 msec ± 2.5, P < .001). Mean T2* of nonhemorrhagic infarctions was marginally elevated by 6% ± 2.5 (37.8 msec ± 2.5, P = .021) in patients and by 8% ± 5 (44.6 msec ± 4.8, P = .012) in canines. In contrast, mean T2 STIR signal intensity (SI) of both hemorrhagic infarctions and nonhemorrhagic infarctions was higher than that in remote myocardium both in patients (hemorrhagic: 37% ± 19, P < .001; nonhemorrhagic: 78% ± 27, P < .001) and in canines (hemorrhagic: 42% ± 22, P < .001; nonhemorrhagic: 65% ± 22, P < .001). Consistent with STIR SI findings, mean T2 of both hemorrhagic (62.0 msec ± 4.9) and nonhemorrhagic (71.7 msec ± 7.3) infarctions in canines was elevated relative to mean T2 of remote myocardium (52.1 msec ± 4.8) by 18% ± 9 and 38% ± 13, respectively (P < .001 for both). CONCLUSION T2* cardiac MR imaging is more suitable than T2 cardiac MR imaging in the detection and characterization of acute reperfusion myocardial hemorrhage. SUPPLEMENTAL MATERIAL http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13122397/-/DC1.

Chronic Manifestation of Postreperfusion Intramyocardial Hemorrhage as Regional Iron Deposition A Cardiovascular Magnetic Resonance Study With Ex Vivo Validation

Background— Intramyocardial hemorrhage frequently accompanies large reperfused myocardial infarctions. However, its influence on the makeup and the ensuing effect on the infarcted tissue during the chronic phase remain unexplored. Methods and Results— Patients (n=15; 3 women), recruited after successful percutaneous coronary intervention for first segment–elevation myocardial infarction, underwent cardiovascular magnetic resonance imaging on day 3 and month 6 after percutaneous coronary intervention. Patients with hemorrhagic (Hemo+) infarctions, as determined by T2* cardiovascular magnetic resonance on day 3 (n=11), showed persistent T2* losses colocalized with scar tissue on the follow-up scans, suggesting chronic iron deposition. T2* values of Hemo+ territories were significantly higher than nonhemorrhagic (Hemo−) and remote territories (P<0.001); however, T2* values of nonhemorrhagic (Hemo−) and remote territories were not different (P=0.51). Canines (n=20) subjected to ischemia-reperfusion injury (n=14) underwent cardiovascular magnetic resonance on days 3 and 56 after ischemia-reperfusion injury. Similarly, sham-operated animals (Shams; n=3) were imaged using cardiovascular magnetic resonance at similar time points. Subsequently, hearts were explanted and imaged ex vivo, and samples of Hemo+, Hemo−, remote, and Sham myocardium were isolated and stained. The extent of iron deposition ([Fe]) within each sample was measured using mass spectrometry. Hemo+ infarcts showed significant T2* losses compared with the other (control) groups (P<0.001), and Perls stain confirmed localized iron deposition. Mean [Fe] of Hemo+ was nearly an order of magnitude greater than that of the control groups (P<0.001), but no significant differences were observed among the control groups. A strong linear relationship was observed between log(T2*) and −log([Fe]); R 2=0.7 and P<0.001. The monoclonal antibody Mac387 stains, along with Perls stains, showed preferential localization of newly recruited macrophages at the site of chronic iron deposition. Conclusions— Hemorrhagic myocardial infarction can lead to iron depositions within the infarct zones, which can be a source of prolonged inflammatory burden in the chronic phase of myocardial infarction.Background— Intramyocardial hemorrhage frequently accompanies large reperfused myocardial infarctions. However, its influence on the makeup and the ensuing effect on the infarcted tissue during the chronic phase remain unexplored. Methods and Results— Patients (n=15; 3 women), recruited after successful percutaneous coronary intervention for first segment–elevation myocardial infarction, underwent cardiovascular magnetic resonance imaging on day 3 and month 6 after percutaneous coronary intervention. Patients with hemorrhagic (Hemo+) infarctions, as determined by T2* cardiovascular magnetic resonance on day 3 (n=11), showed persistent T2* losses colocalized with scar tissue on the follow-up scans, suggesting chronic iron deposition. T2* values of Hemo+ territories were significantly higher than nonhemorrhagic (Hemo−) and remote territories ( P <0.001); however, T2* values of nonhemorrhagic (Hemo−) and remote territories were not different ( P =0.51). Canines (n=20) subjected to ischemia-reperfusion injury (n=14) underwent cardiovascular magnetic resonance on days 3 and 56 after ischemia-reperfusion injury. Similarly, sham-operated animals (Shams; n=3) were imaged using cardiovascular magnetic resonance at similar time points. Subsequently, hearts were explanted and imaged ex vivo, and samples of Hemo+, Hemo−, remote, and Sham myocardium were isolated and stained. The extent of iron deposition ([Fe]) within each sample was measured using mass spectrometry. Hemo+ infarcts showed significant T2* losses compared with the other (control) groups ( P <0.001), and Perls stain confirmed localized iron deposition. Mean [Fe] of Hemo+ was nearly an order of magnitude greater than that of the control groups ( P <0.001), but no significant differences were observed among the control groups. A strong linear relationship was observed between log(T2*) and −log([Fe]); R 2=0.7 and P <0.001. The monoclonal antibody Mac387 stains, along with Perls stains, showed preferential localization of newly recruited macrophages at the site of chronic iron deposition. Conclusions— Hemorrhagic myocardial infarction can lead to iron depositions within the infarct zones, which can be a source of prolonged inflammatory burden in the chronic phase of myocardial infarction.

Determination of location, size, and transmurality of chronic myocardial infarction without exogenous contrast media by using cardiac magnetic resonance imaging at 3 T.

Background—Late-gadolinium–enhanced (LGE) cardiac MRI (CMR) is a powerful method for characterizing myocardial infarction (MI), but the requisite gadolinium infusion is estimated to be contraindicated in ≈20% of patients with MI because of end-stage chronic kidney disease. The purpose of this study is to investigate whether T1 CMR obtained without contrast agents at 3 T could be an alternative to LGE CMR for characterizing chronic MIs using a canine model of MI. Methods and Results—Canines (n=29) underwent CMR at 7 days (acute MI [AMI]) and 4 months (chronic MI [CMI]) after MI. Infarct location, size, and transmurality measured by using native T1 maps and LGE images at 1.5 T and 3 T were compared. Resolution of edema between AMI and CMI was examined with T2 maps. T1 maps overestimated infarct size and transmurality relative to LGE images in AMI (P=0.016 and P=0.007, respectively), which was not observed in CMI (P=0.49 and P=0.81, respectively) at 3 T. T1 maps underestimated infarct size and transmurality relative to LGE images in AMI and CMI (P<0.001) at 1.5 T. Relative to the remote territories, T1 of the infarcted myocardium was increased in CMI and AMI (P<0.05), and T2 of the infarcted myocardium was increased in AMI (P<0.001) but not in CMI (P>0.20) at both field strengths. Histology showed extensive replacement fibrosis within the CMI territories. CMI detection sensitivity and specificity of T1 CMR at 3 T were 95% and 97%, respectively. Conclusions—Native T1 maps at 3 T can determine the location, size, and transmurality of CMI with high diagnostic accuracy. Patient studies are necessary for clinical translation.

Free-breathing, motion-corrected, highly efficient whole heart T2 mapping at 3T with hybrid radial-cartesian trajectory.

To develop and test a time‐efficient, free‐breathing, whole heart T2 mapping technique at 3.0T.

Iron Deposition following Chronic Myocardial Infarction as a Substrate for Cardiac Electrical Anomalies: Initial Findings in a Canine Model

Purpose Iron deposition has been shown to occur following myocardial infarction (MI). We investigated whether such focal iron deposition within chronic MI lead to electrical anomalies. Methods Two groups of dogs (ex-vivo (n = 12) and in-vivo (n = 10)) were studied at 16 weeks post MI. Hearts of animals from ex-vivo group were explanted and sectioned into infarcted and non-infarcted segments. Impedance spectroscopy was used to derive electrical permittivity () and conductivity (). Mass spectrometry was used to classify and characterize tissue sections with (IRON+) and without (IRON-) iron. Animals from in-vivo group underwent cardiac magnetic resonance imaging (CMR) for estimation of scar volume (late-gadolinium enhancement, LGE) and iron deposition (T2*) relative to left-ventricular volume. 24-hour electrocardiogram recordings were obtained and used to examine Heart Rate (HR), QT interval (QT), QT corrected for HR (QTc) and QTc dispersion (QTcd). In a fraction of these animals (n = 5), ultra-high resolution electroanatomical mapping (EAM) was performed, co-registered with LGE and T2* CMR and were used to characterize the spatial locations of isolated late potentials (ILPs). Results Compared to IRON- sections, IRON+ sections had higher, but no difference in. A linear relationship was found between iron content and (p<0.001), but not (p = 0.34). Among two groups of animals (Iron (<1.5%) and Iron (>1.5%)) with similar scar volumes (7.28%±1.02% (Iron (<1.5%)) vs 8.35%±2.98% (Iron (>1.5%)), p = 0.51) but markedly different iron volumes (1.12%±0.64% (Iron (<1.5%)) vs 2.47%±0.64% (Iron (>1.5%)), p = 0.02), QT and QTc were elevated and QTcd was decreased in the group with the higher iron volume during the day, night and 24-hour period (p<0.05). EAMs co-registered with CMR images showed a greater tendency for ILPs to emerge from scar regions with iron versus without iron. Conclusion The electrical behavior of infarcted hearts with iron appears to be different from those without iron. Iron within infarcted zones may evolve as an arrhythmogenic substrate in the post MI period.

Correlation of Scar in Cardiac MRI and High‐Resolution Contact Mapping of Left Ventricle in a Chronic Infarct Model

Endocardial mapping for scars and abnormal electrograms forms the most essential component of ventricular tachycardia ablation. The utility of ultra‐high resolution mapping of ventricular scar was assessed using a multielectrode contact mapping system in a chronic canine infarct model.

Iron-Sensitive Cardiac Magnetic Resonance Imaging for Prediction of Ventricular Arrhythmia Risk in Patients With Chronic Myocardial Infarction Early Evidence

Background—Recent canines studies have shown that iron deposition within chronic myocardial infarction (CMI) influences the electric behavior of the heart. To date, the link between the iron deposition and malignant ventricular arrhythmias in humans with CMI is unknown. Methods and Results—Patients with CMI (n=94) who underwent late-gadolinium-enhanced cardiac magnetic resonance imaging before implantable cardioverter-defibrillator implantation for primary and secondary preventions were retrospectively analyzed. The predictive values of hypointense cores (HIC) in balanced steady-state free precession images and conventional cardiac magnetic resonance imaging and ECG malignant ventricular arrhythmia parameters for the prediction of primary combined outcome (appropriate implantable cardioverter-defibrillator therapy, survived cardiac arrest, or sudden cardiac death) were studied. The use of HIC within CMI on balanced steady-state free precession as a marker of iron deposition was validated in a canine MI model (n=18). Nineteen patients met the study criteria with events occurring at a median of 249 (interquartile range of 540) days after implantable cardioverter-defibrillator placement. Of the 19 patients meeting the primary end point, 18 were classified as HIC+, whereas only 1 was HIC−. Among the cohort in whom the primary end point was not met, there were 28 HIC+ and 47 HIC− patients. Receiver operating characteristic curve analysis demonstrated an additive predictive value of HIC for malignant ventricular arrhythmias with an increased area under the curve of 0.87 when added to left ventricular ejection fraction (left ventricular ejection fraction alone, 0.68). Both cardiac magnetic resonance imaging and histological validation studies performed in canines demonstrated that HIC regions in balanced steady-state free precession images within CMI likely result from iron depositions. Conclusions—Hypointense cores within CMI on balanced steady-state free precession cardiac magnetic resonance imaging can be used as a marker of iron deposition and yields incremental information toward improved prediction of malignant ventricular arrhythmias.

Persistent Microvascular Obstruction After Myocardial Infarction Culminates in the Confluence of Ferric Iron Oxide Crystals, Proinflammatory Burden, and Adverse Remodeling.

Background—Emerging evidence indicates that persistent microvascular obstruction (PMO) is more predictive of major adverse cardiovascular events than myocardial infarct (MI) size. But it remains unclear how PMO, a phenomenon limited to the acute/subacute period of MI, drives adverse remodeling in chronic MI setting. We hypothesized that PMO resolves into chronic iron crystals within MI territories, which in turn are proinflammatory and favor adverse remodeling post-MI. Methods and Results—Canines (n=40) were studied with cardiac magnetic resonance imaging to characterize the spatiotemporal relationships among PMO, iron deposition, infarct resorption, and left ventricular remodeling between day 7 (acute) and week 8 (chronic) post-MI. Histology was used to assess iron deposition and to examine relationships between iron content with macrophage infiltration, proinflammatory cytokine synthesis, and matrix metalloproteinase activation. Atomic resolution transmission electron microscopy was used to determine iron crystallinity, and energy-dispersive X-ray spectroscopy was used to identify the chemical composition of the iron composite. PMO with or without reperfusion hemorrhage led to chronic iron deposition, and the extent of this deposition was strongly related to PMO volume (r>0.8). Iron deposits were found within macrophages as aggregates of nanocrystals (≈2.5 nm diameter) in the ferric state. Extent of iron deposits was strongly correlated with proinflammatory burden, collagen-degrading enzyme activity, infarct resorption, and adverse structural remodeling (r>0.5). Conclusions—Crystallized iron deposition from PMO is directly related to proinflammatory burden, infarct resorption, and adverse left ventricular remodeling in the chronic phase of MI in canines. Therapeutic strategies to combat adverse remodeling could potentially benefit from taking into account the chronic iron-driven inflammatory process.

Assessment of Myocardial Reactivity to Controlled Hypercapnia with Free-breathing T2-prepared Cardiac Blood Oxygen Level–Dependent MR Imaging

PURPOSE To examine whether controlled and tolerable levels of hypercapnia may be an alternative to adenosine, a routinely used coronary vasodilator, in healthy human subjects and animals. MATERIALS AND METHODS Human studies were approved by the institutional review board and were HIPAA compliant. Eighteen subjects had end-tidal partial pressure of carbon dioxide (PetCO2) increased by 10 mm Hg, and myocardial perfusion was monitored with myocardial blood oxygen level-dependent (BOLD) magnetic resonance (MR) imaging. Animal studies were approved by the institutional animal care and use committee. Anesthetized canines with (n = 7) and without (n = 7) induced stenosis of the left anterior descending artery (LAD) underwent vasodilator challenges with hypercapnia and adenosine. LAD coronary blood flow velocity and free-breathing myocardial BOLD MR responses were measured at each intervention. Appropriate statistical tests were performed to evaluate measured quantitative changes in all parameters of interest in response to changes in partial pressure of carbon dioxide. RESULTS Changes in myocardial BOLD MR signal were equivalent to reported changes with adenosine (11.2% ± 10.6 [hypercapnia, 10 mm Hg] vs 12% ± 12.3 [adenosine]; P = .75). In intact canines, there was a sigmoidal relationship between BOLD MR response and PetCO2 with most of the response occurring over a 10 mm Hg span. BOLD MR (17% ± 14 [hypercapnia] vs 14% ± 24 [adenosine]; P = .80) and coronary blood flow velocity (21% ± 16 [hypercapnia] vs 26% ± 27 [adenosine]; P > .99) responses were similar to that of adenosine infusion. BOLD MR signal changes in canines with LAD stenosis during hypercapnia and adenosine infusion were not different (1% ± 4 [hypercapnia] vs 6% ± 4 [adenosine]; P = .12). CONCLUSION Free-breathing T2-prepared myocardial BOLD MR imaging showed that hypercapnia of 10 mm Hg may provide a cardiac hyperemic stimulus similar to adenosine.

Contrast-free T1 mapping at 3T can characterize chronic myocardial infarctions with high diagnostic accuracy

Background Characterizing myocardial infarctions (MIs) on the basis of LGE CMR requires gadolinium infusion, which poses limitations in certain patient populations and imaging workflow. We hypothesized that T1 differences between MI and remote territories at 3T would enable reliable characterization of chronic MI. Methods Canines (n = 29) underwent CMR at 7 days (acute) and 4 months (chronic) following reperfused MIs at 3T (n = 19) and 1.5T (n = 10). Contrast-free T1 maps (MOLLI; 8 TIs with 2 inversion blocks of 3+5 images; minimum TI = 110 ms; ΔTI = 80 ms; TR/TE = 2.2/1.1 ms) and LGE images (IR-prepared FLASH; TI optimized to null remote myocardium; TR/TE = 3.5/1.75 ms) were acquired. MI location, size and transmurality were determined using Mean+5SD criterion relative to remote myocardium. T2 maps (T2-prepared SSFP; T2 preparation times = 0, 24 and 55 ms; TR/TE = 2.8/1.4 ms) were acquired to compare acute and chronic MIs. Commonly used imaging parameters were slice thickness = 6 mm and spatial resolution = 1.3 × 1.3 mm 2. Histological validation was sought to confirm the presence of replacement fibrosis within the chronic infarct zones. Results Contrast-free T1 maps and LGE images of a representative mid-ventricular slice, along with AHA 17-segment bulls-eye plots depicting the MI size and transmurality acquired from a canine scanned imaged 4 months post-MI at 3T are shown in Figure 1. Bland-Altman plots, linear regression plots and receiver-operating characteristic curve comparing T1 maps and LGE images for measuring infarct volume (IV, %LV) and transmurality (IT) in the chronic phase at 3T are also shown. At 3T, T1 maps and LGE images were not different for measuring IV (5.6 ± 3.7% vs. 5.5 ± 3.7%; p = 0.61) and IT (44 ± 15% vs. 46 ± 15%; p = 0.81) in the chronic phase, but were significantly different in the acute phase (IS: 13.3 ± 8.4% vs. 11.6 ± 6.8%, p = 0.007 and IT: 64 ± 19% vs. 56 ± 17%, p = 0.007). At 1.5T, IV and IT were significantly underestimated by T1 maps relative to LGE images during acute (IS: 9.4 ± 5.6% vs. 15.5 ± 9.4%, p < 0.001 and IT: 59 ± 5% vs. 76 ± 6%, p < 0.001) and chronic phases (IS: 2.1 ± 1.2% vs. 4.8 ± 1.8%, p < 0.001 and IT: 47 ± 7% vs. 66 ± 9%, p < 0.001). At 3T and 1.5T, T1 values of the MI remained elevated in both acute (3T: p < 0.001; 1.5T: p < 0.001) and chronic phases (3T: p < 0.001; 1.5T: p = 0.037) compared to remote myocardium (Table 1). At both 3T and 1.5T, relative to the remote myocardium, T2 values of the MI were elevated in the acute phase (p < 0.001 for both cases), but were not different in the chronic phase (3T: p = 0.19, 1.5T: p = 0.55). Ex-vivo TTC and Elastinmodified Masson’s Trichrome (EMT) stainings (Figure 1) confirmed extensive replacement fibrosis within the MI territories at 4 months post MI. Sensitivity and specificity of contrast-free T1 maps at 3T for detecting chronic MIs were 95% and 97%, respectively. Conclusions Contrast-free T1 maps at 3T can determine the location, size and transmurality of chronic MIs with high diagnostic accuracy.