Novel double contrast MRI technique for intramyocardial detection of percutaneously transplanted autologous cells

Baklanov, Dmitri; deMuinck, Ebo D.; Thompson, Craig A.; Pearlman, Justin D.

doi:10.1002/mrm.20292

Cited by 19 publications

(18 citation statements)

References 9 publications

(10 reference statements)

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“…Magnetic resonance imaging (MRI) has been used to track cells longitudinally following direct intramyocardial injection (9,16) and acutely following intracoronary infusion (4). However, the intracoronary route, by its very nature, results in a more diffuse and less dense distribution of cells, which will be more difficult to visualize.…”

mentioning

confidence: 99%

Long-term tracking of bone marrow progenitor cells following intracoronary injection post-myocardial infarction in swine using MRI

Graham

Foltz

Vaags

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

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Magnetic resonance imaging (MRI) can track progenitor cells following direct intramyocardial injection. However, in the vast majority of post-myocardial infarction (MI) clinical trials, cells are delivered by the intracoronary (IC) route, which results in far greater dispersion within the myocardium. Therefore, we assessed whether the more diffuse distribution of cells following IC delivery could be imaged longitudinally with MRI. In 11 pigs (7 active, 4 controls), MI was induced by 90-min balloon occlusion of the left anterior descending coronary artery. Seven (0) days [median (interquartile range)] following MI, bone marrow progenitor cells (BMCs) were colabeled with an iron-fluorophore and a cell viability marker and delivered to the left anterior descending coronary artery distal to an inflated over-the-wire percutaneous transluminal coronary angioplasty balloon. T2*-weighted images were used to assess the location of the magnetically labeled cells over a 6-wk period post-MI. Immediately following cell delivery, hypointensity characteristic of the magnetic label was observed in the infarct border rather than within the infarct itself. At 6 wk, the cell signal hypointensity persisted, albeit with significantly decreased intensity. BMC delivery resulted in significant improvement in infarct volume and ejection fraction (EF): infarct volume in cell-treated animals decreased from 7.1 Ϯ 1.5 to 4.9 Ϯ 1.0 ml (P Ͻ 0.01); infarct volume in controls was virtually unchanged at 4.64 Ϯ 2.1 to 4.39 Ϯ 2.1 ml (P ϭ 0.7). EF in cell-treated animals went from 30.4 Ϯ 5.2% preinjection to 34.5 Ϯ 2.5% 6 wk postinjection (P ϭ 0.013); EF in control animals went from 34.3 Ϯ 4.7 to 31.9 Ϯ 6.8% (P ϭ 0.5). Immunohistochemical analysis revealed intracellular colocalization of the iron fluorophore and cell viability dye with the labeled cells continuing to express the same surface markers as at baseline. MRI can track the persistence and distribution of magnetically labeled BMCs over a 6-wk period following IC delivery. Signal hypointensity declines with time, particularly in the first week following delivery. These cells maintain their original phenotype during this time course. Delivery of these cells appears safe and results in improvement in infarct size and left ventricular ejection fraction. magnetic resonance imaging; myocardial infarction ATHEROSCLEROTIC CORONARY ARTERY disease is widely prevalent and is the commonest cause of premature death in the developed world (21). In patients surviving myocardial infarction (MI), progressive left ventricular (LV) dilation and reduced ejection fraction are major determinants of the development of heart failure and poor long-term survival. Recent studies have assessed the administration of bone marrow progenitor cells (BMCs) as a means of improving cardiac function post-MI and preventing deleterious negative LV remodeling (3,22,24,25,29). Clinical studies have shown that administration of these cells is safe, but their efficacy varies widely, a finding that may largely be explained by differ...

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confidence: 99%

Long-term tracking of bone marrow progenitor cells following intracoronary injection post-myocardial infarction in swine using MRI

Graham

Foltz

Vaags

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

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“…Cellular MRI has emerged as a prime candidate to achieve this (Rogers et al, 2006). However, signal reduction induced by SPIO-based contrast media may deter the unambiguous detection of labeled cells from background tissue comprised of an inherently low signal or signal void (Baklanov, 2004;Cunningham et al, 2005). The attainment of composite contrast properties, using a mixture of SPIO and Gd-DTPA agents, can greatly aid the elimination of this prospect through the use of differential contrast weightings.…”

Section: Discussionmentioning

confidence: 99%

Composite MR contrast agents for conditional cell‐labeling

Marzelli

Fischer²,

Kim³

et al. 2008

Int J Imaging Syst Tech

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Gadolinium-chelates (Gd-DTPA) and superparamagnetic particles of iron oxide (SPIO) are two commonly used MR contrast agents that exhibit inherently different relaxation properties. These two agents have been used to label cells ex-vivo to generate signal contrast with respect to background tissue when introduced to a tissue-of-interest. Assuming minimal mutual interaction between these two agents, we were motivated to investigate the creation of composite relaxation properties by mixing the two in aqueous solutions for conditioning cell labeling. Concentration-dependent relaxivity coefficients were first obtained from each contrast agent, independently, in saline solution at 3 Tesla. These coefficients were then used to predict both the R(1) and R(2) relaxation rates of a composite contrast agent using a linear model combining the effects of both contrast media. The predicted relaxation rates were experimentally confirmed from 25 composite solutions (combinations of SPIO-concentration ranging from 0 to 1 mug/mL and Gd-DTPA-concentration ranging from 0 to 0.20 mM). We show that the combination of SPIO and Gd-DTPA in an aqueous solution exhibits unique and predictable relaxivity properties that are unattainable via the individual use of either agent. The method may be applied to create 'user-tunable' contrast conditions for the visualization of magnetically labeled cells in the context of cell replacement therapy.

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“…The feasibility of visualizing SPIO-labeled cells has also been investigated after intra-vessel delivery. Hypointense signals could be detected in the infarct zone after intracoronary infusion but not after intravenous administration of Feridex-labeled cells [87,88] (Fig. 3).…”

Section: Cardiac Mri For Cell Traffickingmentioning

confidence: 94%

Cell therapy in myocardial infarction: emphasis on the role of MRI

Bogaert

2007

Eur Radiol

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Despite tremendous progress in myocardial infarct (MI) treatment, mortality rates remain substantial. Permanent loss of cardiomyocytes after ischemic injury, results in irreversible loss of myocardial contractility, reduction in ventricular performance, and may initiate the development of dilated heart failure. The discovery that pluripotent progenitor cells bear the capacity to differentiate to mature cardiac cells raised the hope of cell-based regenerative medicine. Engraftment of stem cells in the damaged myocardium, repair and functional improvement appeared suddenly a nearby reality. Promising results in animal models, and preliminary studies reporting the feasibility and safety of adult stem cell therapy in MI patients led to the first double-blinded randomized, placebo-controlled trials. The initial great enthusiasm for this paradigm shift in MI treatment has been tempered by the mainly negative or modestly positive study findings. Before new, larger clinical trials can be initiated, a number of critical questions and issues need to be considered starting with a scrutinized analysis of currently available data to extending our knowledge of the mechanism of scarless myocardial regeneration. Cardiac cell therapy necessitates a multidisciplinary approach, whereby imaging, in particular MRI, and the input of the imaging specialist is crucial to the success of cardiac cell regenerative medicine. MRI is an appealing technique for cell trafficking depicting engraftment, differentiation and survival. Endomyocardial cell administration can be achieved safely with MR fluoroscopy and MRI is without any doubt the most accurate and reproducible technique to measure study end-points.

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Novel double contrast MRI technique for intramyocardial detection of percutaneously transplanted autologous cells

Cited by 19 publications

References 9 publications

Long-term tracking of bone marrow progenitor cells following intracoronary injection post-myocardial infarction in swine using MRI

Long-term tracking of bone marrow progenitor cells following intracoronary injection post-myocardial infarction in swine using MRI

Composite MR contrast agents for conditional cell‐labeling

Cell therapy in myocardial infarction: emphasis on the role of MRI

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