Magnetic Resonance Coronary Angiography

Current Cardiology Reports. Jan, 2003  |  Pubmed ID: 12493161

Magnetic resonance coronary angiography (MRCA) has witnessed tremendous technical advances over the past decade. Although high-quality images of the coronary arteries have been demonstrated, this imaging modality is not performed routinely today. The fundamental properties of the coronary arteries deterring noninvasive imaging are well known. This article provides an overview of the developmental efforts to overcome these challenges, and highlights key technical and clinical advances. The future prospect of MRCA depends on clinical implementation of the technique. In order to meet this challenge, the following issues must be addressed: contrast- and signal-to-noise ratio, temporal and spatial resolution, and scan protocol.

Spiral Magnetic Resonance Coronary Angiography with Rapid Real-time Localization

Journal of the American College of Cardiology. Apr, 2003  |  Pubmed ID: 12679213

A spiral high-resolution coronary artery imaging sequence (SH) interfaced with real-time localization system (RT) has been developed. A clinical study of 40 patients suspected of coronary artery disease (CAD) was conducted. Segmented k-space acquisition techniques have dominated magnetic resonance coronary angiography (MRCA) over the last decade. Although a recent multicenter trial using this technique demonstrated encouraging results, the technique was hampered by low specificity. Spiral k-space acquisition had demonstrated several advantages for MRCA. Therefore, a first clinical trial implementing spiral high-resolution coronary imaging sequence with real-time localization (SH-RT) was performed.A clinical study of 40 patients suspected of CAD undergoing X-ray angiography was conducted to analyze the clinical reliability of this novel imaging system. The SH-RT had been designed to exploit the unique capability of two imaging sequences. The RT allowed a rapid localization of the coronary arteries. Then SH achieved multislice acquisition during a short breath-hold with submillimeter resolution. The MRCA data were analyzed for scan time, anatomic coverage, image quality, and accuracy in detecting CAD. In 40 subjects, SH achieved 0.7 to 0.9 mm resolution with 14-heartbeat breath-holds. Excellent or good image quality was achieved in 78% (263/337) of the coronary segments. Blinded consensus reading among three observers generated sensitivity of 76% and specificity of 91% in the detection of CAD compared with X-ray angiography. The MRCA imaging sequence implementing a novel spiral k-space acquisition technique enabled rapid and reliable imaging of the CAD in submillimeter resolution with short breath-holds.

A Visual Approach for the Accurate Determination of Echocardiographic Left Ventricular Ejection Fraction by Medical Students

Journal of the American Society of Echocardiography : Official Publication of the American Society of Echocardiography. Aug, 2003  |  Pubmed ID: 12878991

Previously published reports show that there is significant intraobserver, interobserver, and interinstitutional variability in the determination of left ventricular (LV) ejection fraction (EF) by echocardiography. With the increased deployment of echocardiography (eg, handheld devices), there exists a need for developing a simple, intuitive approach for evaluating LVEF that allows a wider range of physicians to accurately and rapidly determine LVEF.

Developmental Endothelial Locus-1 (Del-1), a Novel Angiogenic Protein: Its Role in Ischemia

Circulation. Mar, 2004  |  Pubmed ID: 14981004

Developmentally regulated endothelial locus-1 (Del-1) is an extracellular matrix protein that is expressed by endothelial cells during embryological vascular development. We speculated that Del-1 may be reexpressed in ischemia and may be involved in endogenous angiogenesis.

Spiral Magnetic Resonance Coronary Angiography--direct Comparison of 1.5 Tesla Vs. 3 Tesla

Journal of Cardiovascular Magnetic Resonance : Official Journal of the Society for Cardiovascular Magnetic Resonance. 2004  |  Pubmed ID: 15646891

MR coronary angiography (MRCA) has been demonstrated successfully at 3 Tesla (T). However, the advantages remain unclear. No systematic comparison of MRCA between 1.5 T and 3 T has been performed. Therefore, anatomic coverage, image quality, signal-to-noise ratio (SNR), contrast-to-noise ration (CNR), and susceptibility artifacts were compared in 23 subjects.

Dynamic Real-time Architecture in Magnetic Resonance Coronary Angiography--a Prospective Clinical Trial

Journal of Cardiovascular Magnetic Resonance : Official Journal of the Society for Cardiovascular Magnetic Resonance. 2004  |  Pubmed ID: 15646892

A dynamic real-time (dRT) architecture has been developed to address limitations in magnetic resonance coronary angiography (MRCA). A prospective clinical trial of 45 patients suspected of coronary artery disease was conducted to determine clinical utility of this integrated real-time system.

Positive Contrast Magnetic Resonance Imaging of Cells Labeled with Magnetic Nanoparticles

Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. May, 2005  |  Pubmed ID: 15844142

Contrast agents incorporating superparamagnetic iron-oxide nanoparticles have shown promise as a means to visualize labeled cells using MRI. Labeled cells cause significant signal dephasing due to the magnetic field inhomogeneity induced in water molecules near the cell. With the resulting signal void as the means for detection, the particles behave as a negative contrast agent, which can suffer from partial-volume effects. In this paper, a new method is described for imaging labeled cells with positive contrast. Spectrally selective RF pulses are used to excite and refocus the off-resonance water surrounding the labeled cells so that only the fluid and tissue immediately adjacent to the labeled cells are visible in the image. Phantom, in vitro, and in vivo experiments show the feasibility of the new method. A significant linear correlation (r = 0.87, P < 0.005) between the estimated number of cells and the signal was observed.

Early Diagnosis of Hemochromatosis-related Cardiomyopathy with Magnetic Resonance Imaging

Journal of Cardiovascular Magnetic Resonance : Official Journal of the Society for Cardiovascular Magnetic Resonance. 2005  |  Pubmed ID: 16136860

The hallmark of hemochromatosis is the deposition of iron in multiple tissue types, most notably the skin, liver, pancreas, thyroid, and heart. Definitive diagnosis of iron deposition generally requires invasive methods, such as direct tissue biopsy. We describe a 40 year-old woman with end-stage liver disease secondary to hereditary hemochromatosis and alcohol abuse, who was referred to the cardiology service as part of an evaluation for orthotopic liver transplant. The patient had no cardiac history but a dobutamine stress echocardiogram, performed as a portion of the pre-operative cardiac evaluation, could not be completed due to intermittent, supraventricular tachycardia. Additional cardiac testing, including electrocardiography and resting echocardiography, raised suspicion for cardiomyopathy related to hemochromatosis but was non-diagnostic. Cardiac magnetic resonance (MR) of this patient revealed deposition of iron in the myocardium and established the diagnosis of hemachromatosis-related cardiomyopathy. These findings suggest that cardiac MR may be more sensitive than other non-invasive, diagnostic tools in the initial evaluation of hemochromatosis-related cardiomyopathy and may be used as an alternative to myocardial biopsy. We propose that conventional T1- and T2-weighted spin echo MR sequences can be used routinely as non-invasive modalities to assess the presence of iron deposition in the tissues of patients with hemochromatosis.

High-resolution Real-time Spiral MRI for Guiding Vascular Interventions in a Rabbit Model at 1.5 T

Journal of Magnetic Resonance Imaging : JMRI. Nov, 2005  |  Pubmed ID: 16217745

To study the feasibility of a combined high spatial and temporal resolution real-time spiral MRI sequence for guiding coronary-sized vascular interventions.

Noninvasive Assessment of Coronary Vasodilation Using Magnetic Resonance Angiography

Journal of the American College of Cardiology. Jan, 2005  |  Pubmed ID: 15629383

The purpose of this study was to investigate the use of coronary magnetic resonance angiography (MRA) for assessing human epicardial coronary artery vasodilation.

Magnetic Resonance Criteria for Future Trials of Cardiac Resynchronization Therapy

Journal of Cardiovascular Magnetic Resonance : Official Journal of the Society for Cardiovascular Magnetic Resonance. 2005  |  Pubmed ID: 16353444

Current patient selection criteria for Cardiac Resynchronization Therapy (CRT), an efficacious treatment for heart failure, include no measure of disconjugate cardiac contractility other than prolonged QRS on electrocardiogram. Using cardiac magnetic resonance imaging, we examined the roles of cardiac asymmetry, asynchrony, and circumferential strain in DCC with the principal aim of generating a robust numerical index for use in future trials of CRT. Standard cardiac magnetic resonance imaging was done on a GE 1.5 Tesla Signa LX MRI clinical scanner (GE Healthcare, Milwaukee, WI, USA) and analyzed by MASS Analysis (MEDIS, Leiden, The Netherlands). The methods were evaluated in eleven patients with advanced heart failure due to ischemic and non-ischemic cardiomyopathy, who did not qualify under current criteria for CRT, five CRT candidates pre-op and eleven normal subjects. Using t-test and standardized differences (SD = sd/diff, Power (N) = number of patients to reach p < .05) we determined efficacy. Indices of asymmetry and asynchrony (Ism and Isn, respectively) could be measured with accuracy and provided excellent statistical power when used as surrogate markers to delineate heart failure and CRT patients from control subjects. Asymmetry and asynchrony in heart contraction are both critical components of dilated cardiomyopathy that can be improved by CRT. Magnetic resonance asynchrony is efficacious in screening patients and should now be compared with recently published echocardiography data to improve outcome for this costly but valuable therapy.

Images in Cardiovascular Medicine. Cardiac Magnetic Resonance Imaging for Myocarditis: Effective Use in Medical Decision Making

Circulation. Jun, 2006  |  Pubmed ID: 16754807

Collagen Matrices Enhance Survival of Transplanted Cardiomyoblasts and Contribute to Functional Improvement of Ischemic Rat Hearts

Circulation. Jul, 2006  |  Pubmed ID: 16820568

Cardiac cell transplantation is limited by poor graft viability. We aimed to enhance the survival of transplanted cardiomyoblasts using growth factor-supplemented collagen matrices.

Peri-infarct Ischemia Determined by Cardiovascular Magnetic Resonance Evaluation of Myocardial Viability and Stress Perfusion Predicts Future Cardiovascular Events in Patients with Severe Ischemic Cardiomyopathy

Journal of Cardiovascular Magnetic Resonance : Official Journal of the Society for Cardiovascular Magnetic Resonance. 2006  |  Pubmed ID: 17060098

We assessed whether cardiovascular magnetic resonance imaging (CMR) of peri-infarct ischemia provides prognostic information in severe ischemic cardiomyopathy (ICM) patients referred for revascularization.

Real-time Color-flow CMR in Adults with Congenital Heart Disease

Journal of Cardiovascular Magnetic Resonance : Official Journal of the Society for Cardiovascular Magnetic Resonance. 2006  |  Pubmed ID: 17060103

CMR is valuable in the evaluation of congenital heart disease (CHD). Traditional flow imaging sequences involve cardiac and respiratory gating, increasing scan time and susceptibility to arrhythmias. We studied a real-time color-flow CMR system for the detection of flow abnormalities in 13 adults with CHD. All 16 congenital flow abnormalities previously detected by echocardiography were visualized using color-flow CMR, including atrial septal defects (n = 4), ventricular septal defects (n = 9), aortic coarctation (n = 1), Blalock-Taussig shunt (n = 1) and Fontan shunt (n = 1). Real-time color-flow CMR can identify intra- and extra-cardiac flow abnormalities in adults with congenital heart disease.

Dual in Vivo Magnetic Resonance Evaluation of Magnetically Labeled Mouse Embryonic Stem Cells and Cardiac Function at 1.5 T

Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. Jan, 2006  |  Pubmed ID: 16315206

Cell therapy has demonstrated the potential to restore injured myocardium. A reliable in vivo imaging method to localize transplanted cells and monitor their restorative effects will enable a systematic investigation of this therapeutic modality. The dual MRI capability of imaging both magnetically labeled mouse embryonic stem cells (mESC) and their restorative effects on cardiac function in a murine model of acute myocardial infarction is demonstrated. Serial in vivo MR detection of transplanted mESC and monitoring of the mESC-treated myocardium was conducted over a 4-week period using a 1.5 T clinical scanner. During the 4-week duration, the mESC-treated myocardium demonstrated sustained improvement of the left ventricular (LV) ejection fraction and conservation of LV mass. Furthermore, no significant difference of their restorative effects on the cardiac function was created by the magnetic labeling of mESC. Thus, in vivo MRI enables simultaneous detection of transplanted mESC and their therapeutic effect on the injured myocardium.

Indirect Magnetic Resonance Lymphangiography to Assess Lymphatic Function in Experimental Murine Lymphedema

Lymphatic Research and Biology. 2006  |  Pubmed ID: 17394404

Recently, indirect magnetic resonance lymphangiography with gadolinium (Gd) has been demonstrated to offer the potential for safe, high-resolution visualization of the lymphatic vessels, in addition to the lymph nodes. In this study, the potential utility of indirect Gd contrast magnetic resonance imaging of lymphatic vascular function was investigated in the murine tail. Functional imaging of healthy mice is contrasted with the findings in experimentally-induced lymphatic vascular insufficiency.

In Vitro Comparison of the Biological Effects of Three Transfection Methods for Magnetically Labeling Mouse Embryonic Stem Cells with Ferumoxides

Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. Jun, 2007  |  Pubmed ID: 17534917

In vivo MRI of stem cells (SCs) is an emerging application to evaluate the role of cell therapy in restoring the injured myocardium. The high spatial and temporal resolution combined with iron-oxide-based intracellular labeling techniques will provide a sensitive, noninvasive, dual imaging modality for both cells and myocardium. In order to facilitate this novel imaging approach, much effort has been directed towards developing efficient transfection methods. While techniques utilizing poly-L-lysine (PLL), protamine sulfate (PS), and electroporation (ELP) have been proposed, the fundamental biological effects of these methods on mouse embryonic SCs (mESC) have not been investigated systematically. In this study a longitudinal in vitro evaluation of cellular viability, apoptosis, proliferation, and cardiac differentiation of magnetically labeled mESC was conducted. No significant difference was seen in these biological parameters among the three transfection methods. However, cardiac differentiation was most attenuated by ELP, and iron uptake was most effective by PS.

Magnetic Resonance Imaging of Progressive Cardiomyopathic Changes in the Db/db Mouse

American Journal of Physiology. Heart and Circulatory Physiology. May, 2007  |  Pubmed ID: 17122193

The db/db mouse is a well-established model of diabetes. Previous reports have documented contractile dysfunction (i.e., cardiomyopathy) in these animals, although the extant literature provides limited insights into cardiac structure and function as they change over time. To better elucidate the natural history of cardiomyopathy in db/db mice, we performed cardiac magnetic resonance (CMR) scans on these animals. CMR imaging was conducted with a 4.7-T magnet on female db/db mice and control db/+ littermates at 5, 9, 13, 17, and 22 wk of age. Gated gradient echo sequences were used to obtain cineographic short-axis slices from apex to base. From these images left ventricular (LV) mass (LVM), wall thickness, end-diastolic volume (LVEDV), and ejection fraction (LVEF) were determined. Additionally, cardiac [(18)F]fluorodeoxyglucose ([(18)F]FDG) PET scanning, pressure-volume loops, and real-time quantitative PCR on db/db myocardium were performed. Relative to control, db/db mice developed significant increases in LVM and wall thickness as early as 9 wk of age. LVEDV diverged slightly later, at 13 wk. Interestingly, compared with the baseline level, LVEF in the db/db group did not decrease significantly until 22 wk. Additionally, [(18)F]FDG metabolic imaging showed a 40% decrease in glucose uptake in db/db mice. Furthermore, contractile dysfunction was observed in 15-wk db/db mice undergoing pressure-volume loops. Finally, real-time quantitative PCR revealed an age-dependent recapitulation of the fetal gene program, consistent with a myopathic process. In summary, as assessed by CMR, db/db mice develop characteristic structural and functional changes consistent with cardiomyopathy.

Cardiovascular MRI for Stem Cell Therapy

Current Cardiology Reports. Mar, 2007  |  Pubmed ID: 17362684

Stem cell therapy may provide an alternative therapeutic option for severe congestive heart failure (CHF). Despite the promise generated by this novel approach, precise in vivo monitoring of the transplanted cells and of subsequent myocardial restoration remains a challenge. The development of a sensitive, noninvasive imaging technology to track stem cells while assessing cardiac function is critical to monitor therapeutic efficacy. In vivo cardiovascular MRI of stem cells is an emerging application to identify, localize, and monitor stem cells while simultaneously evaluating the restoration of the injured myocardium following stem cell therapy. Furthermore, advances in scanner technology, pulse sequence design, and associated hardware have resulted in real-time guidance of catheter-based intervention to deliver cells accurately to the regions of myocardial injury. These capabilities have positioned MRI as the primary comprehensive imaging modality to monitor cell therapy.

Multimodality Evaluation of the Viability of Stem Cells Delivered into Different Zones of Myocardial Infarction

Circulation. Cardiovascular Imaging. Jul, 2008  |  Pubmed ID: 19808509

We tested the hypothesis that multimodality imaging of mouse embryonic stem cells (mESCs) provides accurate assessment of cellular location, viability, and restorative potential after transplantation into different zones of myocardial infarction.

Human ESC Vs. IPSC-pros and Cons

Journal of Cardiovascular Translational Research. Jun, 2008  |  Pubmed ID: 20559900

Comparison of Reporter Gene and Iron Particle Labeling for Tracking Fate of Human Embryonic Stem Cells and Differentiated Endothelial Cells in Living Subjects

Stem Cells (Dayton, Ohio). Apr, 2008  |  Pubmed ID: 18218820

Human embryonic stem (hES) cells are pluripotent stem cells capable of self-renewal and differentiation into virtually all cell types. Thus, they hold tremendous potential as cell sources for regenerative therapies. The concurrent development of accurate, sensitive, and noninvasive technologies capable of monitoring hES cells engraftment in vivo can greatly expedite basic research prior to future clinical translation. In this study, hES cells were stably transduced with a lentiviral vector carrying a novel double-fusion reporter gene that consists of firefly luciferase and enhanced green fluorescence protein. Reporter gene expression had no adverse effects on cell viability, proliferation, or differentiation to endothelial cells (human embryonic stem cell-derived endothelial cells [hESC-ECs]). To compare the two popular imaging modalities, hES cells and hESC-ECs were then colabeled with superparamagnetic iron oxide particles before transplantation into murine hind limbs. Longitudinal magnetic resonance (MR) imaging showed persistent MR signals in both cell populations that lasted up to 4 weeks. By contrast, bioluminescence imaging indicated divergent signal patterns for hES cells and hESC-ECs. In particular, hESC-ECs showed significant bioluminescence signals at day 2, which decreased progressively over the following 4 weeks, whereas bioluminescence signals from undifferentiated hES cells increased dramatically during the same period. Post-mortem histology and immunohistochemistry confirmed teratoma formation after injection of undifferentiated hES cells but not hESC-ECs. From these data taken together, we concluded that reporter gene is a better marker for monitoring cell viability, whereas iron particle labeling is a better marker for high-resolution detection of cell location by MR. Furthermore, transplantation of predifferentiated rather than undifferentiated hES cells would be more suited for avoiding teratoma formation.

Quantitative Characterization of Myocardial Infarction by Cardiovascular Magnetic Resonance Predicts Future Cardiovascular Events in Patients with Ischemic Cardiomyopathy

Journal of Cardiovascular Magnetic Resonance : Official Journal of the Society for Cardiovascular Magnetic Resonance. 2008  |  Pubmed ID: 18400089

Cardiovascular magnetic resonance (CMR) can provide quantitative data of the myocardial tissue utilizing high spatial and temporal resolution along with exquisite tissue contrast. Previous studies have correlated myocardial scar tissue with the occurrence of ventricular arrhythmia. This study was conducted to evaluate whether characterization of myocardial infarction by CMR can predict cardiovascular events in patients with ischemic cardiomyopathy (ICM).

Noninvasive Assessment of Coronary Vasodilation Using Cardiovascular Magnetic Resonance in Patients at High Risk for Coronary Artery Disease

Journal of Cardiovascular Magnetic Resonance : Official Journal of the Society for Cardiovascular Magnetic Resonance. 2008  |  Pubmed ID: 18513419

Impaired coronary vasodilation to both endothelial-dependent and endothelial-independent stimuli have been associated with atherosclerosis. Direct measurement of coronary vasodilation using x-ray angiography or intravascular ultrasound is invasive and, thus, not appropriate for asymptomatic patients or for serial follow-up. In this study, high-resolution coronary cardiovascular magnetic resonance (CMR) was used to investigate the vasodilatory response to nitroglycerine (NTG) of asymptomatic patients at high risk for CAD.

Multimodal Evaluation of in Vivo Magnetic Resonance Imaging of Myocardial Restoration by Mouse Embryonic Stem Cells

The Journal of Thoracic and Cardiovascular Surgery. Oct, 2008  |  Pubmed ID: 18954646

Mouse embryonic stem cells have demonstrated potential to restore infarcted myocardium after acute myocardial infarction. Although the underlying mechanism remains controversial, magnetic resonance imaging has provided reliable in vivo assessment of functional recovery after cellular transplants. Multimodal comparison of the restorative effects of mouse embryonic stem cells and mouse embryonic fibroblasts was performed to validate magnetic resonance imaging data and provide mechanistic insight.

In Vivo Serial Evaluation of Superparamagnetic Iron-oxide Labeled Stem Cells by Off-resonance Positive Contrast

Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. Dec, 2008  |  Pubmed ID: 19030159

MRI is emerging as a diagnostic modality to track iron-oxide-labeled stem cells. This study investigates whether an off-resonance (OR) pulse sequence designed to generate positive contrast at 1.5T can assess the location, quantity, and viability of delivered stem cells in vivo. Using mouse embryonic stem cell transfected with luciferase reporter gene (luc-mESC), multimodality validation of OR signal was conducted to determine whether engraftment parameters of superparamagnetic iron-oxide labeled luc-mESC (SPIO-luc-mESC) could be determined after cell transplantation into the mouse hindlimb. A significant increase in signal- and contrast-to-noise of the SPIO-luc-mESC was achieved with the OR technique when compared to a gradient recalled echo (GRE) sequence. A significant correlation between the quantity of SPIO-luc-mESC and OR signal was observed immediately after transplantation (R(2) = 0.74, P < 0.05). The assessment of transplanted cell viability by bioluminescence imaging (BLI) showed a significant increase of luciferase activities by day 16, while the MRI signal showed no difference. No significant correlation between BLI and MRI signals of cell viability was observed. In conclusion, using an OR sequence the precise localization and quantitation of SPIO-labeled stem cells in both space and time were possible. However, the OR sequence did not allow evaluation of cell viability.

Comparison of Optical Bioluminescence Reporter Gene and Superparamagnetic Iron Oxide MR Contrast Agent As Cell Markers for Noninvasive Imaging of Cardiac Cell Transplantation

Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging. May-Jun, 2009  |  Pubmed ID: 19034584

In this study, we compared firefly luciferase (Fluc) reporter gene and superparamagnetic iron oxide (Feridex) as cell markers for longitudinal monitoring of cardiomyoblast graft survival using optical bioluminescence imaging (BLI) and magnetic resonance imaging (MRI), respectively.

Imaging Survival and Function of Transplanted Cardiac Resident Stem Cells

Journal of the American College of Cardiology. Apr, 2009  |  Pubmed ID: 19341866

The goal of this study is to characterize resident cardiac stem cells (CSCs) and investigate their therapeutic efficacy in myocardial infarction by molecular imaging methods.

Self-refocused Spatial-spectral Pulse for Positive Contrast Imaging of Cells Labeled with SPIO Nanoparticles

Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. Jul, 2009  |  Pubmed ID: 19449385

MRI has been used extensively to noninvasively track the location of cells labeled with superparamagnetic iron-oxide nanoparticles (SPIOs) in vivo. Typically, SPIOs are employed as a negative contrast agent which makes it difficult to differentiate labeled cells from extraneous sources of inhomogeneity and actual voids in the image. As a result, several novel approaches have been put forth to obtain positive contrast from SPIOs. One technique proposed by Cunningham et al. utilizes spectrally selective pulses to excite and refocus spins in the vicinity of the SPIOs. Although the frequency selectivity of this technique provides effective positive contrast, the lack of slice selectivity results in interfering signal from sources of off-resonance outside the slice of interest. We have developed a self-refocused spatial-spectral (SR-SPSP) pulse to achieve slice-selective spin-echo imaging of off-resonant spins. Using a self-refocused pulse affords flexibility in echo-time selection since the spin echo may be placed at any time after the end of the pulse. The spatial selectivity achieved by the SR-SPSP RF pulse eliminates background signal from out-of-slice regions and reduces the on-resonant water suppression requirements. Phantom and in vivo data demonstrate that positive contrast and slice-selectivity are achieved using this novel RF pulse.

Manganese-guided Cellular MRI of Human Embryonic Stem Cell and Human Bone Marrow Stromal Cell Viability

Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. Oct, 2009  |  Pubmed ID: 19526508

This study investigated the ability of MnCl(2) as a cellular MRI contrast agent to determine the in vitro viability of human embryonic stem cells (hESC) and human bone marrow stromal cells (hBMSC). Basic MRI parameters including T(1) and T(2) values of MnCl(2)-labeled hESC and hBMSC were measured and viability signal of manganese (Mn(2+))-labeled cells was validated. Furthermore, the biological activity of Ca(2+)-channels was modulated utilizing both Ca(2+)-channel agonist and antagonist to evaluate concomitant signal changes. Metabolic effects of MnCl(2)-labeling were also assessed using assays for cell viability, proliferation, and apoptosis. Finally, in vivo Mn(2+)-guided MRI of the transplanted hESC was successfully achieved and validated by bioluminescence imaging.

Magnetic Resonance Imaging of Human Embryonic Stem Cells

Current Protocols in Stem Cell Biology. Aug, 2009  |  Pubmed ID: 19653198

Magnetic resonance imaging (MRI) may emerge as an ideal non-invasive imaging modality to monitor stem cell therapy in the failing heart. This imaging modality generates any arbitrary tomographic view at high spatial and temporal resolution with exquisite intrinsic tissue contrast. This capability enables robust evaluation of both the cardiac anatomy and function. Traditionally, superparamagnetic iron oxide nanoparticle (SPIO) has been widely used for cellular MRI due to SPIO's ability to enhance sensitivity of MRI by inducing remarkable hypointense, negative signal, "blooming effect" on T2*-weighted MRI acquisition. Recently, manganese chloride (MnCl(2)) has been reported by our laboratory for its ability as a contrast agent to track biological activity of viable cells. Hyperintense, positive signals can be achieved from the Mn(2+)-labeled stem cells on T1-weighted MRI acquisition. Cytotoxicity is a potential drawback of Mn(2+) labeling of the cells. However, in our laboratory the labeling method has been optimized to minimize cytotoxic effects. This article describes two different magnetic labeling methods of human embryonic stem cells (hESC) using SPIO and MnCl(2).

Nasal Continuous Positive Airway Pressure Improves Myocardial Perfusion Reserve and Endothelial-dependent Vasodilation in Patients with Obstructive Sleep Apnea

Journal of Cardiovascular Magnetic Resonance : Official Journal of the Society for Cardiovascular Magnetic Resonance. 2010  |  Pubmed ID: 20815898

Obstructive sleep apnea (OSA) has been associated with cardiovascular disease (CVD), but whether OSA is an independent risk factor for CVD is controversial. The purpose of this study is to determine if patients with OSA have subclinical cardiovascular disease that is detectable by multi-modality cardiovascular imaging and whether these abnormalities improve after nasal continuous positive airway pressure (nCPAP).

Positive Contrast with Alternating Repetition Time SSFP (PARTS): a Fast Imaging Technique for SPIO-labeled Cells

Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. Feb, 2010  |  Pubmed ID: 20099331

There has been recent interest in positive-contrast MRI methods for noninvasive tracking of cells labeled with superparamagnetic iron-oxide nanoparticles. Low-tip-angle balanced steady-state free precession sequences have been used for fast, high-resolution, and flow-insensitive positive-contrast imaging; however, the contrast can be compromised by the limited suppression of the on-resonant and fat signals. In this work, a new technique that produces positive contrast with alternating repetition time steady-state free precession is proposed to achieve robust background suppression for a broad range of tissue parameters. In vitro and in vivo experiments demonstrate the reliability of the generated positive contrast. The results indicate that the proposed method can enhance the suppression level by up to 18 dB compared with conventional balanced steady-state free precession.

Molecular Imaging of Stem Cell Transplantation in Myocardial Disease

Current Cardiovascular Imaging Reports. Feb, 2010  |  Pubmed ID: 20396619

Stem cell therapy has been heralded as a novel therapeutic option for cardiovascular disease. In vivo molecular imaging has emerged as an indispensible tool in investigating stem cell biology post-transplantation into the myocardium and in evaluating the therapeutic efficacy. This review highlights the features of each molecular imaging modality and discusses how these modalities have been applied to evaluate stem cell therapy.

Quantitative Tissue Characterization of Infarct Core and Border Zone in Patients with Ischemic Cardiomyopathy by Magnetic Resonance is Associated with Future Cardiovascular Events

Journal of the American College of Cardiology. Jun, 2010  |  Pubmed ID: 20538171

This study evaluates how characterization of tissue heterogeneity of myocardial infarction by cardiovascular magnetic resonance (CMR) is associated with cardiovascular events (CVE) in patients with ischemic cardiomyopathy (ICM).

RevaTen Platelet-rich Plasma Improves Cardiac Function After Myocardial Injury

Cardiovascular Revascularization Medicine : Including Molecular Interventions. May-Jun, 2011  |  Pubmed ID: 21122486

Cell therapy is an exciting area of investigation for repair of injured myocardial tissue. Platelet-rich plasma (PRP) is an autologous fractionation of whole blood containing high concentrations of growth factors including vascular endothelial growth factor and insulin-like growth factor, among many others. PRP has been shown to safely and effectively enhance healing of musculoskeletal tissue primarily by reparative cell signaling. Despite a growing body of evidence on PRP's safety and efficacy, limited studies have been performed using PRP in cardiovascular tissues. Utilizing a murine myocardial permanent ligation and ischemia/reperfusion model, this study sought to determine whether RevaTen PRP (Menlo Park, CA, USA), a proprietary formulation of PRP, improves cardiac function as measured by left ventricular ejection fraction (LVEF).

A Molecular MRI Probe to Detect Treatment of Cardiac Apoptosis in Vivo

Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. Oct, 2011  |  Pubmed ID: 21360750

Cell death by apoptosis is critical in myocardial diseases, and noninvasive detection of early, reversible apoptosis might be useful clinically. Exogenous Annexin-V (ANX) protein binds membrane phosphatidylserine, which is externalized in early apoptosis. A molecular MRI probe was constructed with superparamagnetic iron oxide (SPIO) conjugated to recombinant human ANX (ANX-SPIO). Apoptosis was induced with doxorubicin, a cardiotoxic cancer drug, in culture in neonatal rat ventricular myocytes, cardiac fibroblasts, and mesenchymal stem cells, and in vivo in the mouse heart. ANX-SPIO was validated using T2*-weighted 3T MRI. ANX-SPIO produced T2* signal loss, reflecting iron content, that correlated highly with independent apoptosis markers; bound with high affinity to apoptotic myocytes by competition assay (Ki 69 nM); detected apoptosis in culture much earlier than did TUNEL stain; and revealed fibroblast resistance to apoptosis. With apoptosis in vivo, ANX-SPIO produced diffuse myocardial T2* signal loss that correlated with increased iron stain and caspase activity. Treatment with an alpha-1-adrenergic agonist in vivo reversed apoptosis and eliminated the ANX-SPIO MRI signal. It is concluded that cardiac MRI of ANX-SPIO detects early, nonischemic cardiac apoptosis in culture and in vivo, and can identify reversibly injured cardiac cells in diseased hearts, when treatment is still possible.

In Vivo Molecular MRI of Cell Survival and Teratoma Formation Following Embryonic Stem Cell Transplantation into the Injured Murine Myocardium

Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. Nov, 2011  |  Pubmed ID: 21604295

Embryonic stem cells (ESCs) have shown the potential to restore cardiac function after myocardial injury. Superparamagnetic iron oxide nanoparticles (SPIO) have been widely employed to label ESCs for cellular MRI. However, nonspecific intracellular accumulation of SPIO limits long-term in vivo assessment of the transplanted cells. To overcome this limitation, a novel reporter gene (RG) has been developed to express antigens on the ESC surface. By employing SPIO-conjugated monoclonal antibody against these antigens (SPIO-MAb), the viability of transplanted ESCs can be detected in vivo. This study aims to develop a new molecular MRI method to assess in vivo ESC viability, proliferation, and teratoma formation. The RG is designed to express 2 antigens (hemagglutinin A and myc) and luciferase on the ESC surface. The two antigens serve as the molecular targets for SPIO-MAb. The human and mouse ESCs were transduced with the RG (ESC-RGs) and transplanted into the peri-infarct area using the murine myocardial injury model. In vivo MRI was performed following serial intravenous administration of SPIO-MAb. Significant hypointense signal was generated from the viable and proliferating ESCs and subsequent teratoma. This novel molecular MRI technique enabled in vivo detection of early ESC-derived teratoma formation in the injured murine myocardium.

Dual Manganese-enhanced and Delayed Gadolinium-enhanced MRI Detects Myocardial Border Zone Injury in a Pig Ischemia-reperfusion Model

Circulation. Cardiovascular Imaging. Sep, 2011  |  Pubmed ID: 21719779

Gadolinium (Gd)-based delayed-enhancement MRI (DEMRI) identifies nonviable myocardium but is nonspecific and may overestimate nonviable territory. Manganese (Mn(2+))-enhanced MRI (MEMRI) denotes specific Mn(2+) uptake into viable cardiomyocytes. We performed a dual-contrast myocardial assessment in a porcine ischemia-reperfusion (IR) model to test the hypothesis that combined DEMRI and MEMRI identifies viable infarct border zone (BZ) myocardium in vivo.

Theranostic Effect of Serial Manganese-enhanced Magnetic Resonance Imaging of Human Embryonic Stem Cell Derived Teratoma

Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. Dec, 2011  |  Pubmed ID: 22190225

Although human embryonic stem cell (hESC) hold therapeutic potential, teratoma formation has deterred clinical translation. Manganese (Mn(2+) ) enters metabolically active cells through voltage-gated calcium channels and subsequently, induces T(1) shortening. We hypothesized that serial manganese-enhanced MRI would have theranostic effect to assess hESC survival, teratoma formation, and hESC-derived teratoma reduction through intracellular accumulation of Mn(2+) . Firefly luciferase transduced hESCs (hESC-Lucs) were transplanted into severe combined immunodeficient mouse hindlimbs to form teratoma. The chemotherapy group was injected with MnCl(2) intraperitoneally three times a week. The control group was given MnCl(2) only prior to manganese-enhanced MRI. Longitudinal evaluation by manganese-enhanced MRI and bioluminescence imaging was performed. The chemotherapy group showed significant reduction in the teratoma volume and luciferase activity at weeks 6 and 8. Histology revealed increased proportion of dead cells and caspase 3 positive cells in the chemotherapy group. Systemic administration of MnCl(2) enabled simultaneous monitoring and elimination of hESC-derived teratoma cells by higher intracellular accumulation of Mn(2+) . Magn Reson Med, 2011. © 2011 Wiley Periodicals, Inc.