The MR contrast properties of a series of structurally dissimilar low molecular weight (LMW) gadolinium (Gd) and dysprosium (Dy) chelates have been investigated under controlled experimental conditions in various in vitro test systems. Relaxation analysis (water, pH = 5.8, 37 degrees C, .47 T) demonstrated the high dipolar relaxation efficacy of the tested Gd chelates. The T1 and T2 relaxivities of both metal chelate series decreased with decreasing hydration number, confirming the strong correlation between metal chelate structure and dipolar relaxivity. Susceptibility-induced T2 relaxation, commonly known as the susceptibility effect, is modulated primarily by the magnetic susceptibility and compartmentalization of the contrast agent. The influence of these parameters on the susceptibility effect of Dy diethylenetriamine penta-acetic acid bis-methylamide (DTPA-BMA) and GdDTPA-BMA was investigated in two-compartment in vitro models. In red blood cell suspensions (45% hematocrit, 37 degrees C, .47 T, 2 and 3 mM metal ion concentration), the T2 relaxation efficacy of DyDTPA-BMA was markedly improved due to susceptibility effects that were shown to depend on compartmentalization. As the relaxation ability of GdDTPA-BMA was modulated by the dipolar interactions, compartmentalization was not a prerequisite for its T2 relaxation efficacy. In a coaxial glass system with no intercompartmental water exchange, which eliminated the dipolar relaxation mechanism, DyDTPA-BMA was shown to be the most efficient susceptibility agent because of its higher magnetic susceptibility. The reported one- and two-compartment model studies have demonstrated the different mechanism of action of LMW Gd- and Dy-based contrast agents. Gd chelates are predominantly dipolar relaxation enhancers, whereas Dy chelates are efficient susceptibility agents only in compartmentalized systems.
Purpose: To examine the changes in the longitudinal relaxation times (⌬R1) induced in pig myocardium and blood following injections of 5, 10, and 15 mol mangafodipir trisodium (Mn-DPDP) or MnCl 2 /kg of body weight (b.w.). Materials and Methods:Twelve pigs were divided into two groups, one group receiving MnCl 2 and the other receiving Mn-DPDP. Three consecutive doses of contrast agent (5, 10, and 15 mol/kg of b.w.) were injected in each animal with a 40-minute time interval between each dose. Measurements of T 1 in blood and myocardium were made 5, 15, 25, and 35 minutes after each injection. Additionally, relaxivity measurements in blood samples were performed.Results: An increase in myocardial R1 was observed for both contrast agents at all concentration levels tested. This increase peaked 5 minutes after injection and then declined. An increase could still be detected 35 minutes after injection. The effect was larger when using MnCl 2 than when using Mn-DPDP. Conclusion:The dissociation kinetics of Mn 2ϩ from the DPDP ligand limits the relaxation increase of Mn-DPDP relative to that of MnCl 2. On the other hand, the toxicity of MnCl 2 may exclude it from clinical use.
NC100150-enhanced MRA has the potential for quantification of carotid stenoses and provides an alternative to DSA. The optimal dose of NC100150 was 5-6 mg Fe/kg.
PURPOSE: Gadofluorine M with a fluorescent dye (GdFMCy3) is a lipophilic paramegnetic contrast agent that is readily absorbed by cultured cells. We hypothesized that this agent would be superior to iron oxide based techniques for cell tracking post cell transplantation. METHODS: Embryonic Stem Cell derived cardiac progenitor cells (ES-CPCs) were generated using previously established methods and incubated for 12 hours with 5 mM GdFMCy3, or transfected with iron oxide using published protocols. Cell survival was >95% for cells incubated with both GdFMCy3 and iron. 500,000 cells labelled with GdFMCy3, iron oxide or control (no contrast agent) were directly injected into the myocardium of mice (n=5/group). Mice were scanned over a two week interval post injection at 9.4T using gated T1-weighted sequences (GdFMCy3), T2* weighted GRE sequences (iron oxide) or the positive contrast sequence GRASP (iron oxide). Mice were sacrificed and the hearts sectioned for microscopy. Perl staining and fluorescence microscopy were used to identify iron oxide and GdFMCy3 within the myocardium, respectively. RESULTS: GdFMCy3 labelled cells were successfully identified in vivo at 9.4T (figure panel B). Good correlation between MRI and histology was observed for both cell labels (figure ). Contrast to noise ratios were significantly higher in the GdFMCy3 group relative to the iron oxide group (figure ). CONCLUSIONS: GdFM-Cy3 is readily taken up by stem cells and easily identified by both MRI and fluorescence microscopy. Given its superior contrast to noise ratio GdFM-Cy3 may be an excellent alternative to iron oxide for in vivo detection and tracking of transplanted cells.
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