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Biomedical subjects

Dara L Kraitchman

Publications and source records attributed to Dara L Kraitchman.

At least 19 recordsLinked to original sources

Real-time imaging of regional myocardial function using fast-SENC.

A technique for fast imaging of regional myocardial function using a spiral acquisition in combination with strain-encoded (SENC) magnetic resonance imaging (MRI) is presented in this paper. This technique, which is termed fast-SENC, enables scan durations as short as a single heartbeat. A reduced field of view (FOV) without foldover artifacts was achieved by localized SENC, which selectively excited the region around the heart. The two images required for SENC imaging (low- and high-tuning) were acquired in an interleaved fashion throughout the cardiac cycle to further shorten the scan time. Regional circumferential contraction and longitudinal shortening of both the left ventricle (LV) and right ventricle (RV) were examined in long- and short-axis views, respectively. The in vivo results obtained from five human subjects and five infarcted dogs are presented. The results of the fast-SENC technique in a single heartbeat acquisition were comparable to those obtained by conventional SENC in a long acquisition time. Therefore, fast-SENC may prove useful for imaging during stress or arrhythmia.

Animals↗

Measurement of kinetic parameters in skeletal muscle by magnetic resonance imaging with an intravascular agent.

The purpose of this work was to investigate the use of an intravascular contrast agent to determine perfusion kinetics in skeletal muscle. A two-compartment kinetic model was used to represent the flux of contrast agent between the intravascular space and extravascular extracellular space (EES). The relationship between the image signal-to-noise ratio (SNR) and errors in estimating permeability surface area product (Ktrans), interstitial volume (ve), and plasma volume (vp) for linear and nonlinear curve-fitting methods was estimated from Monte Carlo simulations. Similar results were obtained for both methods. For an image SNR of 60, the estimated errors in these parameters were 10%, 22%, and 17%, respectively. In vivo experiments were conducted in rabbits to examine physiological differences between these parameters in the soleus (SOL) and tibialis anterior (TA) muscles in the hind limb. Values for Ktrans were significantly higher in the SOL (3.2+/-0.9 vs. 2.0+/-0.5x10(-3) min-1), as were values for vp (3.4+/-0.8 vs. 2.1+/-0.7%). Differences in ve for the two muscles (8.7+/-2.2 vs. 8.5+/-1.6%) were not found to be significant. These results demonstrate that relevant physiological metrics can be calculated in skeletal muscle using MRI with an intravascular contrast agent.

Algorithms↗

Dynamic imaging of allogeneic mesenchymal stem cells trafficking to myocardial infarction.

BACKGROUND: Recent results from animal studies suggest that stem cells may be able to home to sites of myocardial injury to assist in tissue regeneration. However, the histological interpretation of postmortem tissue, on which many of these studies are based, has recently been widely debated. METHODS AND RESULTS: With the use of the high sensitivity of a combined single-photon emission CT (SPECT)/CT scanner, the in vivo trafficking of allogeneic mesenchymal stem cells (MSCs) colabeled with a radiotracer and MR contrast agent to acute myocardial infarction was dynamically determined. Redistribution of the labeled MSCs after intravenous injection from initial localization in the lungs to nontarget organs such as the liver, kidney, and spleen was observed within 24 to 48 hours after injection. Focal and diffuse uptake of MSCs in the infarcted myocardium was already visible in SPECT/CT images in the first 24 hours after injection and persisted until 7 days after injection and was validated by tissue counts of radioactivity. In contrast, MRI was unable to demonstrate targeted cardiac localization of MSCs in part because of the lower sensitivity of MRI. CONCLUSIONS: Noninvasive radionuclide imaging is well suited to dynamically track the biodistribution and trafficking of mesenchymal stem cells to both target and nontarget organs.

Animals↗

The effect of intra-aortic balloon counterpulsation on left ventricular functional recovery early after acute myocardial infarction: a randomized experimental magnetic resonance imaging study.

AIMS: We sought to determine whether intra-aortic balloon pump (IABP) counterpulsation improves the recovery of left ventricular (LV) systolic function after reperfused acute myocardial infarction (AMI). METHODS AND RESULTS: Fourteen dogs underwent 90-min coronary artery occlusion followed by reperfusion. Seven animals were randomized to IABP counterpulsation immediately after reperfusion. Tagged, cine, and contrast-enhanced magnetic resonance imaging were used for regional and global LV functional assessment and MI characterization, respectively. Image acquisition was performed at 1 h, 6 h, and 24 h after reperfusion, during which the IABP device was paused. Animals randomized to IABP demonstrated an earlier improvement of LV ejection fraction when compared with controls (25+/-3 vs. 25+/-2% at 1 h, P=0.91; 36+/-3 vs. 26+/-2% at 6 h, P=0.015; and 38+/-3 vs. 35+/-1% at 24 h, P=0.34). Regional functional analyses revealed the same behaviour among non-infarcted risk regions, i.e., earlier circumferential systolic strain improvement in the IABP group than in controls (-5.4+/-0.4 vs. -5.3+/-0.5% at 1 h, P=0.86; -12.1+/-1.0 vs. -6.0+/-0.4% at 6 h, P<0.001; and -13.9+/-1.1% vs. -12.8+/-0.6% at 24 h, P=0.40). Importantly, however, the degree of LV functional recovery 24 h after reperfusion was similar whether IABP counterpulsation was used or not. CONCLUSION: IABP counterpulsation accelerates but does not significantly improve the recovery of LV systolic function after reperfused AMI.

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Enhanced viability imaging: improved contrast in myocardial delayed enhancement using dual inversion time subtraction.

In delayed contrast-enhanced MRI for the assessment of myocardial viability, the TI time in a gated inversion-recovery segmented gradient echo sequence is usually selected to null signal from normal myocardium. Although this TI time generates good contrast between the enhancing infarcted tissue and normal myocardium, there is usually less contrast between the infarct and the blood pool. A subtractive technique utilizing two acquisitions at a long and short TI time is proposed to improve the delineation between infarct-blood and infarct-myocardium. The concept was demonstrated in six mongrel dogs with reperfused myocardial infarction. Infarct-normal myocardium contrast (signal difference) using the proposed enhanced viability imaging (ENVI) technique was 142 +/- 50% (P < 0.001) that of standard magnitude inversion recovery (IR), while at the same TI time for the primary image, infarct-blood contrast, was 247 +/- 136% (P < 0.002) that of magnitude IR. Accounting for increased noise due to the subtraction, signal difference-to-noise ratios (SDNR) did not show a significant change for infarct-myocardium but infarct-blood SDNR for ENVI was 174 +/- 105% that of magnitude-IR (P < 0.03). Thus, marked improvement in the delineation of the infarcted zone was noted over a range of TI times.

Animals↗

Feasibility of integrating high-spatial-resolution 3D breath-hold coronary MR angiography with myocardial perfusion and viability examinations.

The study was institutional review board approved and Health Insurance Portability and Accountability Act compliant. All subjects provided informed consent. Three-dimensional breath-hold coronary magnetic resonance (MR) angiography with use of steady-state free precession was performed in 12 patients up to 20 minutes after 0.2 mmol gadolinium-based contrast material per kilogram of body weight was administered. Within 24 heartbeats, a spatial resolution of up to 1.0 x 1.2 x 2.0 mm was achieved. Sixty-five (82%) of the 79 visualized coronary artery segments had a grade of 3 or 4 on a four-point scale of depiction in which grade 4 indicated excellent depiction. Twenty-seven percent (n = 21) of the 79 segments were assigned a grade of 4; 56% (n = 44), a grade of 3; 16% (n = 13), a grade of 2; and 1% (n = 1), a grade of 1. Coronary MR angiography performed as part of a first-pass myocardial perfusion and viability assessment MR imaging examination is feasible and does not involve additional imaging time.

Adult↗

Accurate and objective infarct sizing by contrast-enhanced magnetic resonance imaging in a canine myocardial infarction model.

OBJECTIVES: To identify an accurate and reproducible method to define myocardial infarct (MI) size, we conducted a study in a closed-chest canine model of acute myocardial infarction, in which MI size was measured using different thresholding techniques and by imaging at different delay times after contrast administration. BACKGROUND: The MI size by contrast-enhanced magnetic resonance imaging (CE-MRI) is directly related to long-term prognosis. However, previous measurements were done using nonuniform methods and tended to overestimate nonviable areas. METHODS: Thirteen animals underwent 90 min of coronary artery occlusion, followed by reperfusion. The CE-MRI data were acquired within 24 h after reperfusion and compared with triphenyltetrazolium chloride pathology. In the first nine animals, images were obtained approximately 15 min after gadolinium diethylene triamine penta-acetic acid (Gd-DTPA) using an inversion-recovery gradient-echo pulse sequence. To identify the most accurate method, MI size by CE-MRI was measured visually and by semi-automatic thresholding techniques, using different criteria. In four additional animals, images were acquired every 6 min until 30 min after Gd-DTPA. RESULTS: Postmortem MI size was 13.5 +/- 2.6% of left ventricular volume. Semi-automatic techniques, using full-width at half-maximum (FWHM) criterion, correlated best with postmortem data (r(2) = 0.94, p < 0.001; results confirmed by Bland-Altman plots). Using FWHM, there was no difference in MI size between different delay times after contrast (15.2 +/- 2.9% to 14.5 +/- 4.2% at 6 and 30 min, respectively; p = NS). CONCLUSIONS: When an objective technique is used to define MI size by CE-MRI, accurate infarct size measurements can be obtained from images obtained up to 30 min after contrast administration.

Animals↗

Late systolic onset of regional LV relaxation demonstrated in three-dimensional space by MRI tissue tagging.

Left ventricular (LV) relaxation entails myocardial deformation that induces LV filling. Yet, the precise mechanisms of the earliest changes in tissue properties that characterize myocardial relaxation remain incompletely understood. Ten healthy volunteers (seven males), 25-43 yr, underwent tagged and cine MRI with high temporal resolution (25-35 ms). Normal strains including radial (E(rr)), circumferential (E(cc)), and longitudinal (E(ll)) strains, shear strains including E(cl) (circumferential-longitudinal), E(cr) (circumferential-radial), and E(rl) (radial-longitudinal), and principal strains (E(1), E(2), and E(3)) were calculated using a displacement field-fitting method. Temporal changes in angular strains indicative of shear and torsion release and normal strains were studied during late systole and early relaxation. The onset of individual relaxation strains was heterogeneous relative to LV filling. Shear strains (E(cr), E(rl), and E(cl)) and radial thinning were first to develop. Times of onset of E(cr), E(rl), E(cl), and E(rr) occurred 108, 93, 67, and 73 ms before aortic valve closure, respectively. E(ll), E(cc), and LV volume change commenced significantly later after the onset of diastolic shear strains and radial thinning. The onset of E(cc), E(ll), and LV volume change was noted 38 ms before aortic valve closure (P < or = 0.05 relative to the onset of shear strains and E(rr)). Myocardial relaxation is characterized by a three-dimensional unfolding deformation that includes release of torsion, shear, and radial thinning beginning before aortic valve closure. This unfolding pattern precedes longitudinal and circumferential elongation and may facilitate early diastolic filling.

Adult↗

Reduction of "no-reflow" phenomenon by intra-aortic balloon counterpulsation in a randomized magnetic resonance imaging experimental study.

OBJECTIVES: Intra-aortic balloon counterpulsation (IABC) can improve post-myocardial infarction (MI) outcomes, but the mechanisms of such effect remain unclear. We hypothesized that IABC augmentation reduces the extent of microvascular obstruction after acute infarction. BACKGROUND: Microvascular obstruction or "no-reflow" (MO) has been shown to negatively influence left ventricular (LV) remodeling after myocardial infarction (MI). METHODS: Seventeen dogs underwent 90 min of coronary artery occlusion followed by reperfusion. Animals were then randomized to either IABC (n = 9) or control (n = 8); IABC augmentation was performed for 24 h after MI. Microvascular obstruction and infarct size by first-pass and delayed contrast-enhanced magnetic resonance imaging (MRI) were measured at 1 and 24 h after reperfusion and compared with postmortem infarct size and MO by microspheres. RESULTS: Microvascular obstruction by MRI, expressed as percent LV mass, decreased significantly in IABC (4.9 +/- 2.2% to 3.6 +/- 1.5%) and increased in controls (3.4 +/- 0.5% to 4.9 +/- 1.1% from 1 to 24 h, respectively; p < 0.001). Similar results were found for MO defined by microspheres. In the control group, MO increased significantly, during 24 h of study (from 8.8 +/- 1.7% to 43.2 +/- 11.1% of infarcted myocardium; p < 0.05), whereas not important change was observed in the IABC group (from 21.3 +/- 7.1% to 25.8 +/- 14.7%; p < 0.05 vs. control at 24 h). Infarct size, measured by MRI, increased in both groups (13.2 +/- 1.8 to 15.5 +/- 2.1 from 1 to 24 h, respectively; p < 0.05). CONCLUSIONS: Intra-aortic balloon counterpulsation augmentation performed after reperfusion improves myocardial perfusion at the tissue level, and reduces the extent of no-reflow caused by microvascular obstruction.

Animals↗

Iron oxide MR contrast agents for molecular and cellular imaging.

Molecular and cellular MR imaging is a rapidly growing field that aims to visualize targeted macromolecules or cells in living organisms. In order to provide a different signal intensity of the target, gadolinium-based MR contrast agents can be employed although they suffer from an inherent high threshold of detectability. Superparamagnetic iron oxide (SPIO) particles can be detected at micromolar concentrations of iron, and offer sufficient sensitivity for T2(*)-weighted imaging. Over the past two decades, biocompatible particles have been linked to specific ligands for molecular imaging. However, due to their relatively large size and clearance by the reticuloendothelial system (RES), widespread biomedical molecular applications have yet to be implemented and few studies have been reproduced between different laboratories. SPIO-based cellular imaging, on the other hand, has now become an established technique to label and detect the cells of interest. Imaging of macrophage activity was the initial and still is the most significant application, in particular for tumor staging of the liver and lymph nodes, with several products either approved or in clinical trials. The ability to now also label non-phagocytic cells in culture using derivatized particles, followed by transplantation or transfusion in living organisms, has led to an active research interest to monitor the cellular biodistribution in vivo including cell migration and trafficking. While most of these studies to date have been mere of the 'proof-of-principle' type, further exploitation of this technique will be aimed at obtaining a deeper insight into the dynamics of in vivo cell biology, including lymphocyte trafficking, and at monitoring therapies that are based on the use of stem cells and progenitors.

Animals↗

Feridex labeling of mesenchymal stem cells inhibits chondrogenesis but not adipogenesis or osteogenesis.

Magnetic resonance (MR) tracking of superparamagnetic iron oxide (SPIO)-labeled cells is a relatively new technique to non-invasively determine the biodistribution and migration of transplanted stem cells. A number of studies have recently reported encouraging results in the use of bone marrow-derived mesenchymal stem cells (MSCs) for repair of a variety of tissues. For MR tracking of SPIO-labeled MSCs, it is important to determine the effect that the magnetic labeling procedure may have on the differentiation capacity of labeled MSCs. Human MSCs were labeled with poly-L-lysine (PLL)-coated Feridex, with Feridex being an FDA-approved SPIO formulation in an off-label application, and assayed for cellular differentiation using five different assays. As compared with unlabeled controls, labeled MSCs exhibited an unaltered viability, proliferated similarly, and underwent normal adipogenic and osteogenic differentiation. However, there was a marked inhibition of chondrogenesis. The blocking of chondrogenic activity was mediated by the Feridex, rather than by the transfection agent (PLL). This is the first report showing Feridex blocking of cellular differentiation down a specific pathway (while not affecting viability and proliferation), and caution should thus be exercised when using Feridex-labeled MSCs for chondrogenic MR tracking studies. On the other hand, no detrimental effects of Feridex-labeling are anticipated for MR-guided osteogenic or adipogenic transplantation studies.

Adipocytes↗

Persistent diastolic dysfunction despite complete systolic functional recovery after reperfused acute myocardial infarction demonstrated by tagged magnetic resonance imaging.

AIMS: This study was designed to characterise both the systolic and diastolic mechanical properties of regions with different degrees of myocardial ischaemic injury after reperfused acute myocardial infarction (AMI). METHODS AND RESULTS: Fourteen dogs underwent 90-min coronary artery occlusion followed by reperfusion. Image acquisition was performed 24 h after reperfusion using three techniques: tagged, first-pass perfusion and delayed-enhancement magnetic resonance imaging (MRI). Systolic circumferential strain and both systolic and diastolic strain rates were calculated in 30 segments/animal. Transmural AMI segments displayed reduced systolic contractility when compared to subendocardial AMI segments (systolic strain = -2.5 +/- 0.5% versus -6.0 +/- 0.9%, P < 0.01 and systolic strain rate = -0.11 +/- 0.12 versus -0.82 +/- 0.16 s(-1), P < 0.01), and both exhibited significant systolic and diastolic dysfunction compared to remote. Moreover, AMI segments presenting with microvascular obstruction ("no-reflow") displayed further compromise of systolic and diastolic regional function (P < 0.05 for both). Importantly, risk region segments only exhibited diastolic impairment (diastolic strain rate = 1.62 +/- 0.14 versus 2.99 +/- 0.13 s(-1), P < 0.001), but not systolic dysfunction compared to remote 24 h after reperfusion. CONCLUSION: Reversibly injured regions can demonstrate persistent diastolic dysfunction despite complete systolic functional recovery after reperfused AMI. Moreover, the presence of no-reflow entails profound systolic and diastolic dysfunction. Finally, tagged magnetic resonance imaging (MRI) strain rate analysis provides detailed mechanical characterisation of regions with different degrees of myocardial ischaemic injury.

Animals↗

Monitoring cell therapy using iron oxide MR contrast agents.

Given the remarkable progress that has recently been obtained in animal studies, the clinical use of stem and progenitor cells to correct or replace defective cell populations may soon become a reality. In order to develop effective cell therapies, the location and distribution of these cells must be determined in a non-invasive manner. Magnetic resonance (MR) tracking of magnetically labeled cells following transplantation or transfusion may fulfill this requirement. Indeed, a series of recent studies indicate that MRI cell tracking has great potential for further evaluation and optimization of cell therapy. Due to its biocompatibility and strong effects on T2(*) relaxation, iron oxide nanoparticles appear to be the contrast agent of choice, and several methods now exist to shuttle sufficient amount of these compounds into cells. Most of the tracking work has been carried out in disease models of the central nervous system, but, recently, the infarcted heart has also received attention. With its excellent spatial resolution and the ability to track labeled cells over prolonged periods of time, MR monitoring of cell therapy is likely to become an important technique in the foreseeable future.

Animals↗

In vivo magnetic resonance imaging of mesenchymal stem cells in myocardial infarction.

BACKGROUND: We investigated the potential of magnetic resonance imaging (MRI) to track magnetically labeled mesenchymal stem cells (MR-MSCs) in a swine myocardial infarction (MI) model. METHODS AND RESULTS: Adult farm pigs (n=5) were subjected to closed-chest experimental MI. MR-MSCs (2.8 to 16x107 cells) were injected intramyocardially under x-ray fluoroscopy. MRIs were obtained on a 1.5T MR scanner to demonstrate the location of the MR-MSCs and were correlated with histology. Contrast-enhanced MRI demonstrated successful injection in the infarct and serial MSC tracking was demonstrated in two animals. CONCLUSIONS: MRI tracking of MSCs is feasible and represents a preferred method for studying the engraftment of MSCs in MI.

Animals↗

Quantitative ischemia detection during cardiac magnetic resonance stress testing by use of FastHARP.

BACKGROUND: Because ECG alterations caused by ischemia cannot be reliably detected in the high-field MRI environment, detection of wall motion abnormalities is often used to ensure patient safety during stress testing. However, an experienced observer is needed to detect these abnormalities. In this study, we investigate the use of fast harmonic phase (FastHARP) MRI for the quantitative, operator-independent detection of the onset of ischemia during acute coronary occlusion. METHODS AND RESULTS: Eight mongrel dogs underwent an acute 2-minute closed-chest coronary artery occlusion while continuous FastHARP images were acquired. Full regional wall strain was determined every other heartbeat in a single short-axis imaging slice. After 5 minutes of reperfusion, a second 2-minute ischemic episode was induced during the acquisition of conventional cine wall-motion images. The time at which ECG alterations were observed during the first ischemic period was recorded. The time from occlusion to the detection of ischemia, based on a consensus of 2 blinded observers, was determined for MRI. No significant ischemia was present in 2 animals. In the remaining animals, the onset of ischemia was detected significantly earlier by FastHARP than by cine MRI (9.5+/-5 versus 33+/-14 seconds, P<0.01). HARP ischemia detection preceded ECG changes, on average, by 54 seconds. CONCLUSIONS: The rapid acquisition and detection of induced ischemia with FastHARP MRI shows promise as a nonsubjective method to diagnose significant coronary lesions during MR stress testing.

Animals↗

Effects of nonionic intravenous contrast agents at PET/CT imaging: phantom and canine studies.

PURPOSE: To investigate the effects of intravenous contrast agents on quantitative values obtained with a combined positron emission tomographic (PET) and computed tomographic (CT) scanner by using several phantoms and a dog. MATERIALS AND METHODS: Fluorine 18 fluorodeoxyglucose (FDG) was mixed with different concentrations of contrast agent with the same syringe (phantom 1), and the phantom was scanned. After image reconstruction with various attenuation maps, radioactivity concentrations were compared. Then, FDG solutions with (phantom 2) or surrounded by (phantom 3) various concentrations of contrast agent were scanned repeatedly, and radioactivity concentration was compared. Finally, PET and CT with and without contrast agent were performed in a dog. PET images were reconstructed by using different attenuation maps, and radioactivity concentrations were compared. The radioactivity concentration on germanium 68 (68Ge)-based corrected images was regarded as standard, and percentage bias, defined as difference divided by measured activity of 68Ge-based corrected images, was assessed. The relationship between the concentration of contrast agent and the percentage bias was assessed with the Pearson coefficient r, and the significance of correlations was evaluated with the Fisher z test. RESULTS: All phantom studies demonstrated that presence of a contrast agent resulted in overestimation of emission data. CT numbers showed a strong positive correlation with the percentage bias in phantoms 2 (r = 0.999) and 3 (r = 0.987); the maximum percentage bias at 1,360 HU reached approximately 45%. These effects were independent of FDG concentration. In a canine model, presence of a contrast agent also increased emission activity, but the percentage bias was less than 15% in the liver and smaller in all other organs except the kidney (26%). CONCLUSION: High concentrations of a contrast agent caused considerable overestimation of apparent tracer activity in phantom studies; however, the emission bias was relatively modest in vivo, except in areas with very high contrast agent concentrations.

Animals↗