Paramagnetic contrast agents in nuclear magnetic resonance medical imaging

Agents useful for influencing the relaxation times in NMR diagnostics, contain at least one paramagnetic, physiologically compatible complex salt comprising a chelate from an open-chain or cyclic complex-forming compound containing organic nitrogen, phosphorus, oxygen and/or sulfur, and a complexed ion of the lanthanide elements of atomic number 57-70 or of the transition metals of atomic numbers 21-29, 42 and 44, and, optionally, an inorganic or organic base or acid, wherein said chelate complex is bound to a biomolecule.

Method of enhancing NMR imaging using chelated paramagnetic ions bound to biomolecules

Determination of myocardial infarct size is important for clinical management of patients with ischemic heart disease and for research on limiting infarct size. Nuclear magnetic resonance (NMR) imaging permits tomographic depiction of the distribution of mobile tissue protons. NMR images have demonstrated high spatial resolution and contrast. To evaluate the potential of this technique in measuring myocardial infarct size, NMR imaging was performed in six canine hearts excised 24 hours after circumflex coronary artery ligation. Before sacrifice, the dogs received i.v. manganous chloride (0.05 mmol/kg). After NMR imaging, the heart were sectioned and the myocardial slices were stained with triphenyl tetrazolium chloride. The pathologically determined infarct size was compared with the infarct size measured by NMR imaging. The correlation was good (regression line slope 1.06; r = 0.94). We conclude that NMR imaging with paramagnetic contrast agents can be used to determine infarct size in excised hearts.

Quantification of experimental myocardial infarction using nuclear magnetic resonance imaging and paramagnetic ion contrast enhancement in excised canine hearts.

The use of manganese-based MRI contrast materials, either manganese salts or chelates, has spanned the entire timeframe of cardiac MRI. However interest in Mn compounds for cardiac MRI has been sporadic because of concerns over cardiotoxicity associated with significant concentration of free Mn2+ and notable success of gadolinium chelates in cardiac application. Initial strategies to overcome cardiotoxicity included chelation of Mn2+ to reduce the concentration of the free ion in vivo, and addition of Ca2+ in combination with Mn2+ to competitively reduce binding of Mn2+ to Ca2+ channels in the heart. Both approaches met with mixed success, but were subsequently discontinued in favor of gadolinium-based approaches. However Mn2+-based media potentially offer unique advantages for characterizing heart pathology over conventional Gd-based contrast media because Mn2+ is taken up by heart cells and retained for hours. Cellular uptake occurs through calcium channels so contrast on delayed images may be interpreted according to regional or global functional status. Since Mn2+ is retained in the heart, Mn-based media can be administered outside the magnet and the contrast pattern measured hours later to provide assessment of uptake. A key issue is whether sufficient accumulation of Mn2+ in heart cells for imaging can occur without cardiotoxicity, and findings to date indicate this is possible. This review examines the current status of Mn2+-enhanced MRI of heart with particular focus on the hypothesis that Mn2+ uptake can be interpreted in terms of heart function.

Applications of manganese-enhanced magnetic resonance imaging (MEMRI) to imaging of the heart

The objective of this study was to determine and compare if MR contrast agents distributed into various compartments can provide estimation of fractional distribution volume (FDV) in normal and infarcted myocardium using inversion recovery echo-planar MR imaging (IR EPI). Three different types of MR agents were investigated: (a) an extracellular agent, GdDTPA-BMA (0.1 mmol/kg); (b) an intravascular agent, GdDTPA-albumin (0.025 mmol/kg); and (c) an intracellular agent, manganese chloride (0.025 mmol/kg). The null point was determined from a series of IR EPI images in which TI was varied. Temporal changes in ΔR1 (ΔR1 = 1/T1post-1/T1pre) were measured during the initial 29–59 min after administration. Rats (n = 24) were subjected to 1-h coronary artery occlusion/reperfusion. Histochemical staining confirmed the presence and location of infarction. GdDTPA-BMA caused increase in ΔR1 of infarction < blood < < normal myocardium. ΔR1 ratios were 1.55 ± 0.08 for infarction and 0.33 ± 0.03 for normal myocardium, consistent with FDV of 0.82 ± 0.04 and 0.18 ± 0.01. The fractional distribution of this agent in normal myocardium approximated the extracellular space of myocardium. GdDTPA-albumin caused increase in ΔR1 of blood < < infarction < < normal myocardium. ΔR1 ratio in normal, but not infarcted, myocardium was constant at 0.10 ± 0.02 and approximated fractional blood volume. MnCl2 caused equivalent increase in ΔR1 of normal and infarcted myocardium. ΔR1 of normal myocardium did not change overtime, whereas ΔR1 of blood rapidly decreased, leading to overestimation of FDV in normal and infarcted myocardium. In conclusion, extracellular, intravascular and intracellular MR contrast agents exhibited different T1-relaxation kinetics in both normal and infarcted myocardium. Constant ΔR1 ratio (myocardium/blood) after administration of MR contrast agent is a prerequisite for estimation of FDV of MR contrast agent in myocardium.

T1-relaxation kinetics of extracellular, intracellular and intravascular MR contrast agents in normal and acutely reperfused infarcted myocardium using echo-planar MR imaging.

Manganese, a trace metal, is known to localize in mitochondria. Because mitochondria are abundant in heart muscle, the possible utility of radioactive manganese as a myocardial imaging agent was examined in 25 rats and six dogs. Myocardial uptake of Mn-54 in rats was found to exceed that of thallium-201; myocardium-to-blood ratios averaged 306:1 versus 48:1 for Tl-201. In the dog, uptake of Mn-54 by ischemic myocardium was reduced by 17-75% compared with normal myocardium. Thus, radioactive manganese appears promising as an intravenous myocardial imaging agent, and might be useful in studying the function of myocardial mitochondria by external imaging.

http://jnm.snmjournals.org/content/18/9/933.full.pdf

Tissue distribution studies with radioactive manganese: a potential agent for myocardial imaging.

Manganese, a trace metal, is known to localize in mitochondria. Because mitochondria are abundant in heart muscle, the possible utility of radioactive manganese as a myocardial imaging agent was examined in 25 rats and six dogs. Myocardial uptake of Mn-54 in rats was found to exceed that of thallium-201; myocardium-to-blood ratios averaged 306:1 versus 48:1 for Tl-201. In the dog, uptake of Mn-54 by ischemic myocardium was reduced by 17 to 75% compared with normal myocardium. Thus, radioactive manganese appears promising as an intravenous myocardial imaging agent, and might be useful in studying the function of myocardial mitochondria by external imaging.

Tissue distribution studies with radioactive manganese: a potential agent for myocardial imaging. [/sup 54/Mn, rats, dogs, /sup 201/Tl]

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Tissue distribution studies with radioactive manganese: a potential agent for myocardial imaging.

Tissue distribution studies with radioactive manganese: a potential agent for myocardial imaging. [/sup 54/Mn, rats, dogs, /sup 201/Tl]