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ABSTRACT: Background- Accurate characterization of the longitudinal trends of myocardial edema and hemorrhage has been previously limited by subjective qualitative methods. We aimed to prospectively characterize the evolution of myocardial edema and hemorrhage post acute myocardial infarction using quantitative measures. Methods and Results- Sixty-two patients were enrolled post primary percutaneous coronary intervention and underwent cardiovascular magnetic resonance on a 1.5-T scanner at 48 hours, 3 weeks, and 6 months. Myocardial edema and hemorrhage were assessed by T2 and T2* mapping, respectively, in both infarct segment (IS) and remote segment (RS). At 48 hours, T2 is higher in IS compared with RS (56.7 ms versus 43.4 ms; P<0.01). At 3 weeks T2 remains higher in IS compared with RS (51.8 ms versus 39.5 ms; P<0.01), and subsequently equalizes by 6 months (39.8 ms versus 39.5 ms; P=nonsignificant). T2 is also increased in RS at day 2 versus 3 weeks (43.4 ms versus 39.5 ms; P<0.01). At 48 hours T2* was reduced in IS compared with RS (32.4 ms versus 37.4 ms; P<0.01). At 3 weeks (IS, 37.7 ms versus RS, 38.4 ms; P=nonsignificant) and 6 months (IS, 37.3 ms versus RS, 38.2 ms; P=nonsignificant), T2* values were equal in both segments. Conclusions- Quantification of myocardial edema and hemorrhage by T2 and T2* mapping is feasible post acute myocardial infarction and demonstrates that hemorrhage resolves faster than edema. Noninfarcted segments can also demonstrate edema in the acute phase possibly due to global hyperemia.
Circulation Cardiovascular Imaging 06/2012; 5(5):566-72. · 5.94 Impact Factor
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ABSTRACT: Currently, the use of cine magnetic resonance imaging (MRI) to identify cardiac quiescent periods relative to the electrocardiogram (ECG) signal is insufficient for producing submillimeter-resolution coronary MR angiography (MRA) images. In this work, the authors perform a time series comparison between tissue Doppler echocardiograms of the interventricular septum (IVS) and concurrent biplane x-ray angiograms. Our results indicate very close agreement between the diastasis gating windows identified by both the IVS and x-ray techniques.
Seven cath lab patients undergoing diagnostic angiograms were simultaneously scanned during a breath hold by ultrasound and biplane x-ray for six to eight heartbeats. The heart rate of each patient was stable. Dye was injected into either the left or right-coronary vasculature. The IVS was imaged using color tissue Doppler in an apical four-chamber view. Diastasis was estimated on the IVS velocity curve. On the biplane angiograms, proximal, mid, and distal regions were identified on the coronary artery (CA). Frame by frame correlation was used to derive displacement, and then velocity, for each region. The quiescent periods for a CA and its subsegments were estimated based on velocity. Using Pearson's correlation coefficient and Bland-Altman analysis, the authors compared the start and end times of the diastasis windows as estimated from the IVS and CA velocities. The authors also estimated the vessel blur across the diastasis windows of multiple sequential heartbeats of each patient.
In total, 17 heartbeats were analyzed. The range of heart rate observed across patients was 47-79 beats per minute (bpm) with a mean of 57 bpm. Significant correlations (R > 0.99; p < 0.01) were observed between the IVS and x-ray techniques for the identification of the start and end times of diastasis windows. The mean difference in the starting times between IVS and CA quiescent windows was -12.0 ms. The mean difference in end times between IVS and CA quiescent windows was -3.5 ms. In contrast, the correlation between RR interval and both the start and duration of the x-ray gating windows were relatively weaker: R = 0.63 (p = 0.13) and R = 0.86 (p = 0.01). For IVS gating windows, the average estimated vessel blurs during single and multiple heartbeats were 0.5 and 0.66 mm, respectively. For x-ray gating windows, the corresponding values were 0.26 and 0.44 mm, respectively.
In this study, the authors showed that IVS velocity can be used to identify periods of diastasis for coronary arteries. Despite variability in mid-diastolic rest positions over multiple steady rate heartbeats, vessel blurring of 0.5-1 mm was found to be achievable using the IVS gating technique. The authors envision this leading to a new cardiac gating system that, compared with conventional ECG gating, provides better resolution and shorter scan times for coronary MRA.
Medical Physics 06/2012; 39(6):3009-18. · 2.83 Impact Factor
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ABSTRACT: Thrombus aspiration (TA) has been shown to improve microvascular perfusion during primary percutaneous coronary intervention (PCI) for patients with ST-segment elevation myocardial infarction (STEMI). The objective of our study was to assess the relationship between TA and myocardial edema, myocardial hemorrhage, microvascular obstruction (MVO) and left ventricular remodeling in STEMI patients using cardiovascular magnetic resonance (CMR).
Sixty patients were enrolled post primary PCI and underwent CMR on a 1.5 T scanner at 48 hours and 6 months. Patients were retrospectively stratified into 2 groups: those that received TA (35 patients) versus that did not receive thrombus aspiration (NTA) (25 patients). Myocardial edema and myocardial hemorrhage were assessed by T2 and T2* quantification respectively. MVO was assessed via a contrast-enhanced T1-weighted inversion recovery gradient-echo sequence.
At 48 hours, infarct segment T2 (NTA 57.9 ms vs. TA 52.1 ms, p = 0.022) was lower in the TA group. Also, infarct segment T2* was higher in the TA group (NTA 29.3 ms vs. TA 37.8 ms, p = 0.007). MVO incidence was lower in the TA group (NTA 88% vs. TA 54%, p = 0.013).At 6 months, left ventricular end-diastolic volume index (NTA 91.9 ml/m2 vs. TA 68.3 ml/m2, p = 0.013) and left ventricular end systolic volume index (NTA 52.1 ml/m2 vs. TA 32.4 ml/m2, p = 0.008) were lower and infarct segment systolic wall thickening was higher in the TA group (NTA 3.5% vs. TA 74.8%, p = 0.003).
TA during primary PCI is associated with reduced myocardial edema, myocardial hemorrhage, left ventricular remodeling and incidence of MVO after STEMI.
Journal of Cardiovascular Magnetic Resonance 03/2012; 14:19. · 3.72 Impact Factor
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ABSTRACT: To investigate varied manifestations of persistent microvascular obstruction (PMO) and acute left ventricular (LV) remodeling in an experimental reperfused myocardial infarction (MI) using MRI.
In eleven Yorkshire pigs an acute MI was produced through a 90-minute balloon occlusion of the middle left anterior descending coronary artery, followed by reperfusion. All animals underwent MRI examinations on a 1.5T system including a SSFP functional study, first pass myocardial perfusion (FPMP), T1 preparation Look-Locker and delayed contrast-enhanced MRI (DE-MRI). Imaging was performed immediately post-intervention (day 0) and at days 7-9. In four animals a repeat MRI examination was performed at day 2 as well. Upon study completion, animals underwent histological analysis including infarct assessment with triphenyltetrazolium chloride (TTC).
Following reperfusion, Thrombolysis In Myocardial Infarction (TIMI) Flow grade 3 was achieved in all animals, demonstrated by repeat angiography following balloon deflation (day 0). Various MR appearances of PMO were noticed including predominance in the subendocardial region, a central core within the infarcted tissue and also multiple separate clusters. In ten of eleven animals PMO was demonstrated as a persistent hypo-enhanced area in FPMP and DE-MRI, and identified as bright regions in later T1 difference images. In one animal PMO was identified only at day 2. At day 7-9 PMO could be identified on early DE-MRI at 5-15 minutes post Gd injection but not on late DE-MRI and T1 difference images after 45-60 minutes post-contrast. A larger volume of PMO and MI at day 2 was noted in comparison to data from day 0 but the difference was not statistically significant. An increased end-diastolic LV volume (EDV) without changes in end-systolic LV volume (ESV) and LV mass at end-diastolic phase (LVM) was observed at day 7-9 in comparison to data from day 0. There was good correlation between the relative extent of persistent MO in the infarcted myocardium (% MO/MI) and EDV at day 7-9 (r=0.83, n=10, P=0.003). MI was confirmed in all animals by TTC staining and/or histology.
A variable MR appearance of persistent microvascular obstruction is observed during a short time course MRI study of reperfused acute MI. Acute negative LV remodeling was closely related to the relative extent of persistent microvascular obstruction within the infarct myocardium.
Quantitative imaging in medicine and surgery. 03/2012; 2(1):12-20.
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Journal of Cardiovascular Magnetic Resonance 02/2012; 14 Suppl 1:O105. · 3.72 Impact Factor
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Journal of Cardiovascular Magnetic Resonance 02/2012; 14 Suppl 1:P29. · 3.72 Impact Factor
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Mihaela Pop,
Maxime Sermesant,
Garry Liu,
Jatin Relan,
Tommaso Mansi,
Alan Soong,
Jean-Marc Peyrat,
Michael V Truong,
Paul Fefer,
Elliot R McVeigh,
Herve Delingette, Alexander J Dick,
Nicholas Ayache,
Graham A Wright
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ABSTRACT: Cardiac computer models can help us understand and predict the propagation of excitation waves (i.e., action potential, AP) in healthy and pathologic hearts. Our broad aim is to develop accurate 3D MR image-based computer models of electrophysiology in large hearts (translatable to clinical applications) and to validate them experimentally. The specific goals of this paper were to match models with maps of the propagation of optical AP on the epicardial surface using large porcine hearts with scars, estimating several parameters relevant to macroscopic reaction-diffusion electrophysiological models. We used voltage-sensitive dyes to image AP in large porcine hearts with scars (three specimens had chronic myocardial infarct, and three had radiofrequency RF acute scars). We first analyzed the main AP waves' characteristics: duration (APD) and propagation under controlled pacing locations and frequencies as recorded from 2D optical images. We further built 3D MR image-based computer models that have information derived from the optical measures, as well as morphologic MRI data (i.e., myocardial anatomy, fiber directions and scar definition). The scar morphology from MR images was validated against corresponding whole-mount histology. We also compared the measured 3D isochronal maps of depolarization to simulated isochrones (the latter replicating precisely the experimental conditions), performing model customization and 3D volumetric adjustments of the local conductivity. Our results demonstrated that mean APD in the border zone (BZ) of the infarct scars was reduced by ~13% (compared to ~318 ms measured in normal zone, NZ), but APD did not change significantly in the thin BZ of the ablation scars. A generic value for velocity ratio (1:2.7) in healthy myocardial tissue was derived from measured values of transverse and longitudinal conduction velocities relative to fibers direction (22 cm/s and 60 cm/s, respectively). The model customization and 3D volumetric adjustment reduced the differences between measurements and simulations; for example, from one pacing location, the adjustment reduced the absolute error in local depolarization times by a factor of 5 (i.e., from 58 ms to 11 ms) in the infarcted heart, and by a factor of 6 (i.e., from 60 ms to 9 ms) in the heart with the RF scar. Moreover, the sensitivity of adjusted conductivity maps to different pacing locations was tested, and the errors in activation times were found to be of approximately 10-12 ms independent of pacing location used to adjust model parameters, suggesting that any location can be used for model predictions.
Medical image analysis 12/2011; 16(2):505-23. · 3.09 Impact Factor
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Transplantation 07/2011; 92(2):e6-e7. · 4.00 Impact Factor
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ABSTRACT: Left ventricular remodeling as a result of acute myocardial infarction (AMI) is associated with significant morbidity, leading to cardiovascular dysfunction, disability, and death. Despite successful revascularization, coronary vasodilatory dysfunction has been shown in infarcted and remote myocardium of patients following AMI. Our study explored the utility of a T(2)-based blood-oxygen-level-dependent approach in probing regional and longitudinal fluctuations in vasodilatory function in a porcine model of AMI at 3 T. Ten pigs underwent MRI in control state and at day 2, weeks 1-6 following 90 min occlusion followed by reperfusion. The remote myocardium exhibited vasodilatory dysfunction at weeks 1 and 2 that gradually recovered, whereas the infarct zone showed no vasodilatory alterations. Our study suggests that microvascular alterations occurring in infarcted and remote myocardium after AMI might serve as an indicator of adverse left ventricular remodeling. The blood-oxygen-level-dependent technique using quantitative T(2) could potentially be a useful noninvasive tool to evaluate novel therapeutic strategies aimed at limiting vasoconstriction and improving coronary flow reserve after AMI.
Magnetic Resonance in Medicine 05/2011; 66(6):1739-47. · 2.96 Impact Factor
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ABSTRACT: Pathophysiological responses after acute myocardial infarction include edema, hemorrhage, and microvascular obstruction along with cellular damage. The in vivo evolution of these processes simultaneously throughout infarct healing has not been well characterized. The purpose of our study was to quantitatively monitor the time course of these mechanisms by MRI in a porcine model of myocardial infarction. Ten pigs underwent MRI before coronary occlusion with subgroups studied at day 2 and weeks 1, 2, 4, and 6 post-infarction. Tissue characterization was performed using quantitative T2 and T2* maps to identify edema and hemorrhage, respectively. Contrast-enhanced MRI was used for infarct/ microvascular obstruction delineation. Inflammation was reflected by T2 fluctuations, however at day 2, edema and hemorrhage had counter-acting effects on T2. Hemorrhage (all forms) and mineralization (calcium) could be identified by T2* in the presence of edema. Simultaneous resolution of microvascular obstruction and T2* abnormality suggested that the two phenomenon were closely associated during the healing process. Our study demonstrates that quantitative T2 and T2* mapping techniques allow regional, longitudinal, and cross-subject comparisons and give insights into histological and tissue remodeling processes. Such in vivo characterization will be important in grading severity and evaluating treatment strategies for myocardial infarction, potentially improving clinical outcomes.
Magnetic Resonance in Medicine 02/2011; 66(4):1129-41. · 2.96 Impact Factor
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ABSTRACT: In utero hematopoietic cell transplantation offers a means of early intervention for the treatment of diseases before birth. Delivery of cells to the yolk sac is a minimally invasive approach that results in low levels of chimerism. However, there is little information on the optimal doses, timing of delivery, and migration of transplanted cells from the yolk sac into the fetus.
Varying cell doses of mesenchymal stromal cells or bone marrow mononuclear cells labeled with fluorescent supraparamagnetic iron oxide nanoparticles and a fluorescent intracellular dye, 5- and 6-([(4-chloromethyl)benzoyl]-amino) tetramethylrhodamine, were transplanted under ultrasound guidance to the yolk sacs of day 25 or day 35 canine fetuses. Ex vivo whole body fluorescence imaging and microscopy of tissue sections were correlated with the presence of iron oxide in injected and control fetuses.
Day 25 and day 35 recipients showed similar survival rates after injection of cells into yolk sacs, although increased fetal morality was associated with cell doses greater than 10 cells/kg to day 25 fetuses. The fluorescence and iron oxide signals were predominantly localized to the abdominal regions, with no fluorescence visible in yolk sacs. Microscopy of tissues revealed colocalization of fluorophore with iron oxide in donor cells detected in the fetal livers and bone marrow of recipients 7 and 17 days after receiving mesenchymal stromal cells or bone marrow mononuclear cells.
These studies demonstrated that cells injected into the yolk sacs of early gestation canine fetuses migrate to recipient hematopoietic tissues. Thus, yolk sac injection offers a safe and effective approach for engraftment of cells to fetal hematopoietic tissues.
Transplantation 02/2011; 91(7):723-30. · 4.00 Impact Factor
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ABSTRACT: We hypothesized that multicontrast late-enhancement (MCLE) MRI would improve the identification of papillary muscle involvement (PM-MI) in patients with myocardial infarction (MI), compared with conventional late gadolinium enhancement (LGE) MRI using the inversion recovery fast gradient echo (IR-FGRE) technique. Cardiac LGE-MRI studies using both MCLE and IR-FGRE pulse sequences were performed on a 1.5 Tesla (T) MRI system in 23 patients following MI. In all patients, PM-MI was confirmed by the diagnostic criteria as outlined below: (a) the increased signal intensity of PM was the same or similar to that of adjacent hyper-enhanced left ventricular (LV) infarct segments; and (b) the hyper-enhanced PM region was limited to the PM area defined by precontrast cine images of steady-state free precession (SSFP). Visual contrast score was rated according to the differentiation between LV blood pool and hyper-enhanced infarct myocardium. Quantitative contrast-noise ratios (CNR) of infarct relative to blood pool and viable myocardium were also measured on MCLE and IR-FGRE images. Of these 23 patients, 13 studies demonstrated primarily involvement of the territories of the right coronary (RCA, 8 patients) and/or left circumflex (LCX, 5 patients) arteries and 10 involved the territories of left anterior descending artery (LAD) with some LCX involvement. Although both IR-FGRE and MCLE determined the presence and extent of LV MI, better visual contrast scores were achieved in MCLE (2.9 ± 0.3) compared with IR-FGRE (1.6 ± 0.8, P < 0.001). The CNRs of infarct relative to LV blood pool showed a significant statistical difference (n = 23, P < 0.00001) between MCLE (16.2 ± 7.2) and IR-FGRE images (4.8 ± 4.1), which is consistent with the result of visual contrast scores between infarct and LV blood pool. The CNRs of infarct versus viable myocardium did not demonstrate a significant statistical difference (n = 23, P = 0.61) between MCLE (14.4 ± 7.0) and IR-FGRE images (13.6 ± 6.1). MCLE clearly demonstrated PM-MI in all cases (100%, 23/23) while only 39% (9/23) could be visualized on the corresponding IR-FGRE images. In conclusion, MCLE imaging provides better contrast between blood pool and infarct myocardium, thus improving the determination of PM-MI.
Journal of Magnetic Resonance Imaging 01/2011; 33(1):211-6. · 2.70 Impact Factor
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Nigel R Munce,
Bradley H Strauss,
Xiuling Qi,
Max J Weisbrod,
Kevan J Anderson,
General Leung,
John D Sparkes,
Julia Lockwood,
Ronen Jaffe,
Jagdish Butany,
Aaron A Teitelbaum,
Beiping Qiang, Alexander J Dick,
Graham A Wright
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ABSTRACT: The purpose of this study was to characterize the 3-dimensional structure of intravascular and extravascular microvessels during chronic total occlusion (CTO) maturation in a rabbit model.
Intravascular microchannels are an important component of a CTO and may predict guidewire crossability. However, temporal changes in the structure and geographic localization of these microvessels are poorly understood.
A total of 39 occlusions were created in a rabbit femoral artery thrombin model. Animals were sacrificed at 2, 6, 12, and 24 weeks (n > or =8 occlusions per time point). The arteries were filled with a low viscosity radio-opaque polymer compound (Microfil) at 150 mm Hg pressure. Samples were scanned in a micro-computed tomography system to obtain high-resolution volumetric images. Analysis was performed in an image processing package that allowed for labeling of multiple materials.
Two distinct types of microvessels were observed: circumferentially oriented "extravascular" and longitudinally oriented "intravascular" microvessels. Extravascular microvessels were evident along the entire CTO length and maximal at the 2-week time point. There was a gradual and progressive reduction in extravascular microvessels over time, with very minimal microvessels evident beyond 12 weeks. In contrast, intravascular microvessel formation was delayed, with peak vascular volume at 6 weeks, followed by modest reductions at later time points. Intravascular microvessel formation was more prominent in the body compared with that in the proximal and distal ends of the CTO. Sharply angulated connections between the intravascular and extravascular microvessels were present at all time points, but most prominent at 6 weeks. At later time points, the individual intravascular microvessels became finer and more tortuous, although the continuity of these microvessels remained constant beyond 2 weeks.
Differences are present in the temporal and geographic patterns of intravascular and extravascular microvessel formation during CTO maturation.
JACC. Cardiovascular imaging 08/2010; 3(8):797-805. · 14.29 Impact Factor
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ABSTRACT: Myocardial hypoperfusion following percutaneous coronary intervention, termed "no-reflow", may be initiated by distal coronary embolization. This study examined the effects of distal embolization on the extent and timing of inflammation and platelet activation in an experimental model of coronary no-reflow.
A no-reflow model was established in 9 Yorkshire pigs by injecting incremental doses of biologically inert polystyrene microspheres into the left anterior descending artery every 20 minutes via a transit catheter. A control group included 3 pigs that received corresponding intra-coronary boluses of normal saline. At predefined time points, coronary sinus blood samples were drawn and immediately analyzed by flow cytometry analysis for a panel of white blood cell and platelet activation markers, and the inflammatory cytokine TNFalpha.
No-reflow was achieved after delivery of 1,169,000+/-303,000 (range: 680,000 to 2,600,000) microspheres. In the distal embolization group, there were significant increases above baseline values in polymorphonuclear-platelet aggregates (146%-218%), in monocyte-platelet aggregates (51%-94%) and in TNFalpha levels (54%-84%) at multiple time points prior to no- reflow (15% cumulative dose and higher). For Annexin A5, there was a significant increase at 52% of cumulative dose (177% above baseline). Controls only showed one significant increase above baseline value for polymorphonuclear-platelet aggregates at the time of the last injection.
Widespread activation of interacting inflammatory and coagulation pathways following microsphere embolization occurred prior to the onset of angiographic no-reflow. This activation pattern cannot be attributed to prolonged coronary sinus instrumentation. Interactions between white blood cells (polymorphonuclears and monocytes) and platelets likely play an important role in the pathogenesis of no-reflow following distal embolization and may represent important therapeutic targets.
Thrombosis Research 07/2010; 126(1):50-5. · 2.44 Impact Factor
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John J Graham,
Warren D Foltz,
Andrea K Vaags,
Michael R Ward,
Yuesong Yang,
Kim A Connelly,
Ram Vijayaraghavan,
Jay S Detsky,
Margaret R Hough,
Duncan J Stewart,
Graham A Wright, Alexander J Dick
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ABSTRACT: Magnetic resonance imaging (MRI) can track progenitor cells following direct intramyocardial injection. However, in the vast majority of post-myocardial infarction (MI) clinical trials, cells are delivered by the intracoronary (IC) route, which results in far greater dispersion within the myocardium. Therefore, we assessed whether the more diffuse distribution of cells following IC delivery could be imaged longitudinally with MRI. In 11 pigs (7 active, 4 controls), MI was induced by 90-min balloon occlusion of the left anterior descending coronary artery. Seven (0) days [median (interquartile range)] following MI, bone marrow progenitor cells (BMCs) were colabeled with an iron-fluorophore and a cell viability marker and delivered to the left anterior descending coronary artery distal to an inflated over-the-wire percutaneous transluminal coronary angioplasty balloon. T2*-weighted images were used to assess the location of the magnetically labeled cells over a 6-wk period post-MI. Immediately following cell delivery, hypointensity characteristic of the magnetic label was observed in the infarct border rather than within the infarct itself. At 6 wk, the cell signal hypointensity persisted, albeit with significantly decreased intensity. BMC delivery resulted in significant improvement in infarct volume and ejection fraction (EF): infarct volume in cell-treated animals decreased from 7.1 +/- 1.5 to 4.9 +/- 1.0 ml (P < 0.01); infarct volume in controls was virtually unchanged at 4.64 +/- 2.1 to 4.39 +/- 2.1 ml (P = 0.7). EF in cell-treated animals went from 30.4 +/- 5.2% preinjection to 34.5 +/- 2.5% 6 wk postinjection (P = 0.013); EF in control animals went from 34.3 +/- 4.7 to 31.9 +/- 6.8% (P = 0.5). Immunohistochemical analysis revealed intracellular colocalization of the iron fluorophore and cell viability dye with the labeled cells continuing to express the same surface markers as at baseline. MRI can track the persistence and distribution of magnetically labeled BMCs over a 6-wk period following IC delivery. Signal hypointensity declines with time, particularly in the first week following delivery. These cells maintain their original phenotype during this time course. Delivery of these cells appears safe and results in improvement in infarct size and left ventricular ejection fraction.
AJP Heart and Circulatory Physiology 04/2010; 299(1):H125-33. · 3.71 Impact Factor
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ABSTRACT: Despite the widespread use of pharmacological and/or interventional reperfusion therapies, recovery of cardiac function in myocardial infarction (MI) patients is often modest or even absent. Unlike classical pharmacological treatments, the use of progenitor cells could potentially restore functional tissue in regions that otherwise would form only scar. However, a major limitation of autologous cell therapy is the deleterious influence of age and cardiac risk factors on progenitor cell activity.
The ENACT-AMI trial is a phase IIb, double-blind, randomized placebo-controlled trial, using transplantation of autologous early endothelial progenitor cells (EPCs) for patients who have suffered large MI. Circulating mononuclear cells (MNCs) are obtained by apheresis and subjected to differential culture for 3 days to select a population of highly regenerative, endothelial-like, culture modified MNCs (E-CMMs), often referred to as "early EPCs." A total of 99 patients will be randomized to placebo (Plasma-Lyte A), autologous E-CMMs, or E-CMMs transfected with human endothelial nitric oxide synthase delivered by coronary injection into the infarct-related artery. The primary efficacy end point is change from baseline to 6 months in global left ventricular ejection fraction by cardiac MRI; secondary endpoints include regional wall motion, wall thickening, infarct volume, time to clinical worsening, and quality of life.
This will be the first clinical trial to include a strategy designed to enhance the function of autologous progenitor cells by overexpressing endothelial nitric oxide synthase, and the first to use combination gene and cell therapy for the treatment of cardiac disease.
American heart journal 03/2010; 159(3):354-60. · 4.65 Impact Factor
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ABSTRACT: To determine the accuracy of multicontrast late enhancement imaging (MCLE) in the assessment of myocardial viability and wall motion compared to the conventional wall motion and viability cardiac magnetic resonance imaging (MRI) pulse sequences.
Forty-one patients with suspected myocardial infarction were studied. Patients underwent assessment of cardiac function with cine steady-state free-precession (SSFP), followed by late gadolinium enhancement (LGE) imaging using inversion recovery gradient echo scanning (IR-GRE) sequence and MCLE. MCLE was compared to cine SSFP in the assessment of wall motion, ejection fraction (EF), left ventricular (LV) mass, LV end-diastolic volume (EDV), and to IR-GRE for measuring infarct size.
MCLE, IR-GRE, and SSFP imaging demonstrated excellent agreement in the assessment of EF, LV infarct size, and LV mass (r > 0.95, P < 0.001 for all measures), as well as in the assessment of wall motion (kappa statistic 0.75).
MCLE provided coregistered images for the assessment of viability and wall motion without loss of accuracy in the assessment of quantitative cardiac parameters. MCLE provides accurate quantitative cardiac assessment with reduced scan times compared to the conventional sequences and thus may be used as an alternative to conventional cine SSFP and IR-GRE imaging.
Journal of Magnetic Resonance Imaging 10/2009; 30(4):771-7. · 2.70 Impact Factor
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ABSTRACT: Delayed enhancement MRI (DE-MRI) can be used to identify myocardial infarct (MI). Classification of MI into the infarct core and heterogeneous periphery (called the gray zone) on conventional inversion-recovery gradient echo (IR-GRE) DE-MRI images has been related to inducibility for ventricular tachycardia. However, this classification is sensitive to image noise, depends on the signal intensity characteristics in a remote region of myocardium, and requires manual contours of the endocardial border. Image analysis and fuzzy clustering techniques were developed to analyze images acquired using a multicontrast delayed enhancement (MCDE) sequence in order characterize the infarct zones. The MCDE analysis is automated and uses data fitting of signal intensities acquired at multiple inversion times. In a study of 15 patients with chronic MI, the gray zones derived from IR-GRE and MCDE images were comparable. The variability in the gray zone size associated with random noise and operator input was significantly reduced using the MCDE-based analysis compared to the IR-GRE-based analysis. In summary, the MCDE approach yields a more reproducible measure of the infarct core and gray zones on any given data set.
IEEE transactions on medical imaging. 10/2009; 28(10):1606-14.
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ABSTRACT: Takotsubo cardiomyopathy often presents to the cardiac catheterization laboratory masquerading as acute ST-elevation myocardial infarction (STEMI). Some of these patients present in shock secondary to dynamic left ventricular outflow tract (LVOT) obstruction. The typical patient is an elderly, hypertensive female with sigmoid deformity of the intraventricular septum. The management of hemodynamic instability in these patients is different from patients with STEMI. While hemodynamic instability in the setting of STEMI is usually treated with inotropic agents and intraaortic balloon counterpulsation, these therapies can increase LVOT pressure gradients in patients with takotsubo cardiomyopathy and lead to deepening of shock and worse outcomes. Thus accurate diagnosis and correct management are essential to prevent mortality in these patients, who will usually go on to have good long-term outcomes. This case report and literature review addresses the clinical characteristics, outcome, and management of these patients.
Journal of Interventional Cardiology 08/2009; 22(5):444-52. · 1.18 Impact Factor
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Ronen Jaffe,
General Leung,
Nigel R Munce,
Amandeep S Thind,
Howard Leong-Poi,
Kevan J T Anderson,
Xiuling Qi,
Judy Trogadis,
Ariella Nadler,
Davida Shiff,
Jamie Saperia,
Julia Lockwood,
Chaim Jacobs,
Beiping Qiang,
Aaron Teitelbaum, Alexander J Dick,
John D Sparkes,
Jagdish Butany,
Graham A Wright,
Bradley H Strauss
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ABSTRACT: We sought to perform the first systematic study of the natural history of chronic total arterial occlusions (CTOs) in an experimental model.
Angioplasty of CTOs has low success rates. The structural and perfusion changes during CTO maturation, which may adversely affect angioplasty outcome, have not been systematically studied.
Occlusions were created in 63 rabbit femoral arteries by thrombin injection. Histology, contrast-enhanced magnetic resonance imaging, relative blood volume (RBV) index, and micro-computed tomography imaging were analyzed at 2, 6, 12, and 18 to 24 weeks.
Early changes were characterized by an acute inflammatory response and negative arterial remodeling, with >70% reduction of arterial cross-sectional area (CSA) from 2 to 6 weeks. Intraluminal neovascularization of the CTO occurred with a 2-fold increase in total (media + intima) microvessel CSA from 2 to 6 weeks (0.014 +/- 0.002 mm2 to 0.023 +/- 0.005 mm2, p = 0.0008) and a 3-fold increase in RBV index (5.1 +/- 1.9% to 16.9 +/- 2.7%, p = 0.0008). However at later time periods, there were significant reductions in both RBV (3.5 +/- 1.1%, p < 0.0001) and total microvessel CSA (0.017 +/- 0.002 mm2, p = 0.011). Micro-computed tomography imaging demonstrated a corkscrew-like recanalization channel at the proximal end at 6 weeks that regressed at later time points. These vascular changes were accompanied by a marked decrease in proteoglycans and accumulation of a collagen-enriched extracellular matrix, particularly at the entrance ("proximal fibrous cap").
This study is the first to systematically analyze compositional changes occurring during CTO maturation, which may underlie angioplasty failure. Negative remodeling, regression of intraluminal channels, and CTO perfusion, together with the accumulation of dense collagen, may represent important targets for novel therapeutic interventions.
Journal of the American College of Cardiology 04/2009; 53(13):1148-58. · 14.16 Impact Factor
