Mid-diastolic left ventricular volume and mass: Normal values for coronary computed tomography angiography.

BACKGROUND: The adoption of prospectively ECG-triggered acquisition coronary computed tomography angiography (CTA) has resulted in the inability to measure left ventricle (LV) end-diastolic volume and LV ejection fraction. However other prognostic measures such as LV mass and LV mid-diastolic volume (LVMDV) can still be assessed. The objective of this study is to establish normal reference values for LVMDV and LV mass. METHODS: Left ventricular mid-diastolic volumes and LV mass were prospectively measured in 2647 consecutive 'normal' patients undergoing prospectively ECG-triggered coronary CTA. Patients with known coronary artery disease (prior myocardial infarction or prior revascularization), heart failure, congenital heart disease, heart transplant or prior cardiac surgery were excluded. Commercially available software was used to calculate the LVMDV and LV mass. RESULTS: Among the 2647 patient cohort (mean age = 58 years, 54% men), the mean LVMDV indexed for body surface area was 57.5 ± 15.3 mL/m2 and 64.5 ± 20.2 mL/m2 for women and men, respectively. The mean indexed LV mass was 52.2 ± 10.9 g/m2 for women and 63.6 ± 13.7 g/m2 for men. Indexed LVMDV decreased with increasing age. The presence of hypertension, diabetes and obstructive coronary artery disease did not have a clinically relevant impact on these values. Age and sex specific upper limits of normal were defined. CONCLUSION: We establish normal reference ranges for LVMDV and LV mass using prospectively ECG-triggered coronary CTA. These benchmarks may identify patients at increased risk of adverse events, supporting the potential for clinical reporting of these metrics.

Regenerative cell imaging in cardiac repair.

Heart disease continues to be a leading cause of death in the Western world. Although strides have been made in prevention and management of coronary artery disease, lost myocardium after an ischemic event remains at the core of the morbidity and the mortality. Poor regenerative capacity of the myocardium has led to the study of cell-based therapies to restore anatomical, functional, and viable myocardium. To that end, stem cells are undifferentiated cells that are self-renewing, clonogenic, and pluripotent and therefore ideal for the restorative job. However, to refine the technique of cell-based therapy, in vivo molecular assessment is imperative to monitor cell survival and their effect on myocardial restoration. Direct imaging of the behaviour of cells after implantation into living subjects can offer great insight into their mechanisms of action, and their therapeutic efficacy. In this article we explore current knowledge of various imaging modalities that have been used to assess in vivo cellular and molecular events after administration of stem cells in injured myocardium. The goal of the article is to provide a comprehensive overview of the literature, highlight various imaging modalities, and suggest some of the key concepts on the horizon in cardiac stem cell imaging.

Evolution of right ventricular function post-acute ST elevation myocardial infarction.

PURPOSE: To characterize the evolution of right ventricular (RV) function post-myocardial infarction (MI), to describe the culprit vessel involved with RV injury and to assess the concordance between RV injury on magnetic resonance imaging (MRI) and RV infarct on electrocardiogram (EKG). MATERIALS AND METHODS: Thirty-one patients underwent cardiovascular magnetic resonance (CMR) examinations at three time frames post-ST elevation MI (STEMI). RESULTS: Of those with an initial normal scan, RV function did not significantly change over time (60.6 ± 6.3, 57.8 ± 6.0, 55.4 ± 5.7, P > 0.05). However, in those whose RVEF (RV ejection fraction) was initially low, it significantly increased from the first scan to the third scan (46.2 ± 3.6, 50 ± 6.6, 51.3 ± 5.2, P < 0.01). Post-hoc testing revealed a significant difference between the 48-hour and the 6-month scan, and between the 48-hour and the 3-week scan; however, there was no significant difference between the 3-week and 6-month scans. Interestingly, 23% of patients with low RVEF at baseline had the left anterior descending (LAD) as the culprit vessel. Only 15% of the low RVEF at baseline group were classified as having an RVMI by EKG criteria. CONCLUSIONS: The optimal timepoint to assess for RV injury via CMR may be 3 weeks post-acute MI. Standard EKG criteria may underestimate RV injury when compared to CMR.

Correlation of late gadolinium enhancement MRI and quantitative T2 measurement in cardiac sarcoidosis.

PURPOSE: To investigate the potentially improved detection and quantification of cardiac involvement using novel late-gadolinium-enhancement (LGE) cardiac magnetic resonance imaging (MRI) and quantitative T2 measurement to achieve better myocardial tissue characterization in systemic sarcoidosis. MATERIALS AND METHODS: Twenty-eight patients with systemic sarcoidosis underwent a cardiac magnetic resonance imaging (CMR) study on a 1.5T system. Precontrast CMR included left ventricular (LV) and right ventricular (RV) function and quantitative T2 measurement. Postcontrast LGE-MRI included inversion-recovery fast-gradient-echo (IR-FGRE) and multicontrast late-enhancement imaging (MCLE). RESULTS: LV functional parameters were normal in all patients (LVEF=61.2±8.5%) including with cardiac involvement (LVEF=59.4±12.1%) and without (LVEF=61.7±7.5%) while the average RV function was comparatively decreased (RVEF=48.0±6.6%, P<0.0001). 21.4% of patients had cardiac involvement showing patchy or multiple focal hyperenhancement patterns in LV free wall, papillary muscles (PM), or interventricular septum. In two cases with PM involvement, the PM abnormal LGE foci were only observed on MCLE. For precontrast T2 measurements, a significantly decreased T2 measurement was observed in regions demonstrating LGE, compared to the LGE-negative group (focal LGE-positive regions vs. negative: 40.0±2.4 msec vs. 53.0±2.6 msec, P<0.0001). CONCLUSION: LGE-MRI can identify cardiac involvement in systemic sarcoidosis. MCLE might be more sensitive at detecting subtle myocardial lesion. The decreased T2 observed in cardiac sarcoid may reflect its inactive phase, thus might provide a noninvasive method for monitoring disease activity or therapy.

Comparison of the frequencies of myocardial edema determined by cardiac magnetic resonance in diabetic versus nondiabetic patients having percutaneous coronary intervention for ST elevation myocardial infarction.

The specific mechanisms by which diabetes may affect the myocardial tissue response to ischemia are unclear. Our objective was to prospectively quantify the degree of myocardial edema in diabetics versus nondiabetics with ST elevation myocardial infarction using cardiac magnetic resonance. Fifty-two patients (16 diabetics and 36 nondiabetics) were enrolled after primary percutaneous coronary intervention and underwent cardiac magnetic resonance on a 1.5-T scanner at 48 hours and 6 months. Myocardial edema was quantified using a T2 mapping technique, and infarct size and microvascular obstruction size were assessed by way of a contrast-enhanced T1-weighted inversion recovery gradient-echo sequence. The infarct segment T2 was elevated in diabetics compared with nondiabetics (59.0 ± 8.0 vs 50.8 ± 3.1 ms, p <0.001) at 48 hours. Multivariate analysis demonstrated that diabetes (p <0.001) and symptom-to-balloon time (p = 0.04) were independent predictors of the degree of acute myocardial edema. Infarct size was nonsignificantly higher in the diabetic group at 48 hours (26.9 ± 9.4% vs 20.1 ± 10.1% of myocardium, p = 0.07) and 6 months (17.1 ± 6.3% vs 13.4 ± 6.1% of myocardium, p = 0.09). Microvascular obstruction size was equivalent in both groups, and there was a trend toward lower myocardial salvage index in diabetics (34.2 ± 11.8 vs 49.6 ± 13.4, p = 0.08). In conclusion, diabetes is associated with increased myocardial edema in the acute phase after primary percutaneous coronary intervention. Our results offer insight into the complex processes that characterize myocardial tissue response to injury in diabetic patients.

Automatic functional analysis of left ventricle in cardiac cine MRI.

RATIONALE AND OBJECTIVES: A fully automated left ventricle segmentation method for the functional analysis of cine short axis (SAX) magnetic resonance (MR) images was developed, and its performance evaluated with 133 studies of subjects with diverse pathology: ischemic heart failure (n=34), non-ischemic heart failure (n=30), hypertrophy (n=32), and healthy (n=37). MATERIALS AND METHODS: The proposed automatic method locates the left ventricle (LV), then for each image detects the contours of the endocardium, epicardium, papillary muscles and trabeculations. Manually and automatically determined contours and functional parameters were compared quantitatively. RESULTS: There was no significant difference between automatically and manually determined end systolic volume (ESV), end diastolic volume (EDV), ejection fraction (EF) and left ventricular mass (LVM) for each of the four groups (paired sample t-test, α=0.05). The automatically determined functional parameters showed high correlations with those derived from manual contours, and the Bland-Altman analysis biases were small (1.51 mL, 1.69 mL, -0.02%, -0.66 g for ESV, EDV, EF and LVM, respectively). CONCLUSIONS: The proposed technique automatically and rapidly detects endocardial, epicardial, papillary muscles' and trabeculations' contours providing accurate and reproducible quantitative MRI parameters, including LV mass and EF.

The effect of percutaneous coronary intervention of chronically totally occluded coronary arteries on left ventricular global and regional systolic function.

BACKGROUND: Percutaneous coronary intervention (PCI) is frequently attempted to open chronic total occlusions (CTOs) and restore epicardial coronary flow. Data suggest adverse outcomes in the case of PCI failure. We hypothesized that failure to open a CTO might adversely affect regional cardiac function and promote deleterious cardiac remodelling, and success would improve global and regional cardiac function assessed using cardiac magnetic resonance and velocity vector imaging. METHODS: Thirty patients referred for PCI to a CTO underwent cardiac magnetic resonance examination before and after the procedure. Left ventricular function and transmural extent of infarction was assessed in these patients. Regional cardiac function using Velocity Vector Imaging version 3.0.0 (Siemens) was assessed in 20 patients. RESULTS: Successful CTO opening (thrombolysis in myocardial infarction 3 flow) occurred in 63% of patients. Left ventricular ejection fraction significantly increased after successful PCI (50 ± 13% to 54 ± 11%; P < 0.01). Global longitudinal strain (GLS) fell significantly in the failed group (Δ = -25 ± 17%; P = 0.02) in contrast with successful PCI in which GLS did not change (Δ 20 ± 32%; P = 0.17). GLS rate followed a pattern similar to GLS (failed, Δ -30 ± 17%; P < 0.01 vs success Δ 25 ± 48%; P = 0.34). In contrast, radial and circumferential strain/strain rate were not different between groups after success/failed PCI. CONCLUSIONS: Regional cardiac function assessment using velocity vector imaging showed a significant decline in GLS and GLS rate in patients in whom PCI failed to open a CTO, with no change in global measures of cardiac function.

Quantification of fibrosis in infarcted swine hearts by ex vivo late gadolinium-enhancement and diffusion-weighted MRI methods.

Many have speculated that MRI signal characteristics can be used to identify regions of heterogeneous infarct associated with an arrhythmogenic substrate; however, direct evidence of this relationship is limited. The aim of this study was to demonstrate the remodelling characteristics of fibrosis by means of histology and high-resolution MR imaging. For this purpose, we performed whole-mount histology in heart samples (n = 9) collected from five swine at six weeks post-infarction and compared the extent of fibrosis in the infarcted areas delineated in these histological images with that obtained ex vivo by MRI using late gadolinium-enhancement (LGE) and diffusion-weighted imaging (DWI) methods. All MR images were obtained at a submillimetre resolution (i.e., voxel size of 0.6×0.6×1.2 mm(3)). Specifically, in the histology images, we differentiated moderate fibrosis (consisting of a mixture of viable and non-viable myocytes, known as border zone, BZ) from severe fibrosis (i.e., the dense scar). Correspondingly, tissue heterogeneities in the MR images were categorized by a Gaussian mixture model into healthy, BZ and scar. Our results showed that (a) both MRI methods were capable of qualitatively distinguishing sharp edges between dense scar and healthy tissue from regions of heterogeneous BZ; (b) the BZ and dense scar areas had intermediate-to-high increased values of signal intensity in the LGE images and of apparent diffusion coefficient in the DWI, respectively. In addition, as demonstrated by the Picrosirius Red and immunohistochemistry stains, the viable bundles in the BZ were clearly separated by thin collagen strands and had reduced expression of Cx43, whereas the core scar was composed of dense fibrosis. A quantitative analysis demonstrated that the comparison between BZ/scar extent in LGE and DWI to the corresponding areas identified in histology yielded very good correlations (i.e., for the scar identified by LGE, R(2) was 0.96 compared to R(2) = 0.93 for the scar identified in ADC maps, whereas the BZ had R(2) = 0.95 for the correlation between LGE and histology compared to R(2) = 0.91 obtained for ADC). This novel study represents an intermediate step in translating such research to the in vivo stages, as well as in establishing the best and most accurate MR method to help identify arrhythmia substrate in patients with structural heart disease.

Multi-contrast late enhancement CMR determined gray zone and papillary muscle involvement predict appropriate ICD therapy in patients with ischemic heart disease.

BACKGROUND: Myocardial infarct heterogeneity indices including peri-infarct gray zone are predictors for spontaneous ventricular arrhythmias events after ICD implantation in patients with ischemic heart disease. In this study we hypothesize that the extent of peri-infarct gray zone and papillary muscle infarct scores determined by a new multi-contrast late enhancement (MCLE) method may predict appropriate ICD therapy in patients with ischemic heart disease. METHODS: The cardiovascular magnetic resonance (CMR) protocol included LV functional parameter assessment and late gadolinium enhancement (LGE) CMR using the conventional method and MCLE post-contrast. The proportion of peri-infarct gray zone, core infarct, total infarct relative to LV myocardium mass, papillary muscle infarct scores, and LV functional parameters were statistically compared between groups with and without appropriate ICD therapy during follow-up. RESULTS: Twenty-five patients with prior myocardial infarct for planned ICD implantation (age 64±10 yrs, 88% men, average LVEF 26.2±10.4%) were enrolled. All patients completed the CMR protocol and 6-46 months follow-up at the ICD clinic. Twelve patients had at least one appropriate ICD therapy for ventricular arrhythmias at follow-up. Only the proportion of gray zone measured with MCLE and papillary muscle infarct scores demonstrated a statistically significant difference (P < 0.05) between patients with and without appropriate ICD therapy for ventricular arrhythmias; other CMR derived parameters such as LVEF, core infarct and total infarct did not show a statistically significant difference between these two groups. CONCLUSIONS: Peri-infarct gray zone measurement using MCLE, compared to using conventional LGE-CMR, might be more sensitive in predicting appropriate ICD therapy for ventricular arrhythmia events. Papillary muscle infarct scores might have a specific role for predicting appropriate ICD therapy although the exact mechanism needs further investigation.

MRI manifestations of persistent microvascular obstruction and acute left ventricular remodeling in an experimental reperfused myocardial infarction.

PURPOSE: To investigate varied manifestations of persistent microvascular obstruction (PMO) and acute left ventricular (LV) remodeling in an experimental reperfused myocardial infarction (MI) using MRI. METHODS: 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). RESULTS: 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. CONCLUSION: 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.

Ultrasound-guided identification of cardiac imaging windows.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Characterizing myocardial edema and hemorrhage using quantitative T2 and T2* mapping at multiple time intervals post ST-segment elevation myocardial infarction.

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.

Thrombus aspiration during primary percutaneous coronary intervention is associated with reduced myocardial edema, hemorrhage, microvascular obstruction and left ventricular remodeling.

BACKGROUND: 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). METHODS: 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. RESULTS: 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). CONCLUSION: TA during primary PCI is associated with reduced myocardial edema, myocardial hemorrhage, left ventricular remodeling and incidence of MVO after STEMI.

Imaging the failing right ventricle.

PURPOSE OF REVIEW: This article will review the noninvasive modalities currently available for imaging the right ventricle, including two-dimensional echocardiography, cardiac magnetic resonance (CMR), multidetector computed tomography (MDCT), radionuclide ventriculography (RNV) and PET. RECENT FINDINGS: Improvements in established imaging techniques, as well as development of newer imaging modalities, have shed light on the right ventricle's adaptation to pressure and volume overload states and have allowed better prognostication in patients with right ventricular failure (RVF). SUMMARY: As therapies are developed to alter the natural history of RVF, a better understanding of the imaging modalities for the assessment of right ventricular morphology and function is needed. This review will provide an approach to investigating the patient with suspected RVF and highlight the strengths and weakness of each imaging modality.

Construction of 3D MR image-based computer models of pathologic hearts, augmented with histology and optical fluorescence imaging to characterize action potential propagation.

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.

Myocardial BOLD imaging at 3 T using quantitative T2: application in a myocardial infarct model.

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.

Quantitative tracking of edema, hemorrhage, and microvascular obstruction in subacute myocardial infarction in a porcine model by MRI.

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.

Migration of cells from the yolk sac to hematopoietic tissues after in utero transplantation of early and mid gestation canine fetuses.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Papillary muscle involvement in myocardial infarction: initial results using multicontrast late-enhancement MRI.

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.

Intravascular and extravascular microvessel formation in chronic total occlusions a micro-CT imaging study.

OBJECTIVES: 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. BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Differences are present in the temporal and geographic patterns of intravascular and extravascular microvessel formation during CTO maturation.