Myocardial manganese elevation and proton relaxivity enhancement with manganese dipyridoxyl diphosphate. Ex vivo assessments in normally perfused and ischemic guinea pig hearts

Brurok, Heidi; Skoglund, Trine; Berg, Kirsti; Skarra, Sissel; Karlsson, Jan; Jynge, Per

doi:10.1002/(sici)1099-1492(199910)12:6<364::aid-nbm585>3.3.co;2-q

Cited by 20 publications

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“…35 Furthermore, MnDPDP has been successfully utilized for imaging cardiac ischemia. 34,[36][37][38] It is interesting to note that much of the Mn 2þ in MnDPDP comes off the chelate slowly after administration, 39 which implies some of the tissue enhancement detected with MnDPDP was due to Mn 2þ .…”

Section: Manganese Is An Intracellular Contrast Agentsupporting

confidence: 63%

Manganese‐enhanced magnetic resonance imaging (MEMRI): methodological and practical considerations

et al. 2004

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Manganese-enhanced MRI (MEMRI) is being increasingly used for MRI in animals due to the unique T 1 contrast that is sensitive to a number of biological processes. Three specific uses of MEMRI have been demonstrated: to visualize activity in the brain and the heart; to trace neuronal specific connections in the brain; and to enhance the brain cytoarchitecture after a systemic dose. Based on an ever-growing number of applications, MEMRI is proving useful as a new molecular imaging method to visualize functional neural circuits and anatomy as well as function in the brain in vivo. Paramount to the successful application of MEMRI is the ability to deliver Mn 2þ to the site of interest at an appropriate dose and in a time-efficient manner. A major drawback to the use of Mn 2þ as a contrast agent is its cellular toxicity. Therefore, it is critical to use as low a dose as possible. In the present work the different approaches to MEMRI are reviewed from a practical standpoint. Emphasis is given to the experimental methodology of how to achieve significant, yet safe, amounts of Mn 2þ to the target areas of interest.

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Section: Manganese Is An Intracellular Contrast Agentsupporting

confidence: 63%

Manganese‐enhanced magnetic resonance imaging (MEMRI): methodological and practical considerations

et al. 2004

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“…Work has been performed demonstrating that MEMRI may be useful to report on cell viability [10,11]. The activity of brain and heart has been monitored with MEMRI due to the ability of Mn 2+ to enter excitable cells on voltage gated calcium channels [12][13][14][15][16].…”

Section: Introductionsupporting

confidence: 93%

“…Manganese dipyridoxaldiphosphate (MnDPDP) is presently FDA approved for liver imaging for negative enhancement of tumors in the liver [33]. In addition, there has been much work demonstrating the usefulness of MnDPDP for imaging cardiac ischemia [10,11,28,34]. While a detailed description of work with MnDPDP is beyond the scope of this review, it is interesting to note that much of the Mn 2+ comes off of the chelate slowly after administration [35].…”

Section: Systemic Administration Of Manganese Leads To Useful Mri Conmentioning

confidence: 99%

“…There has been some work imaging the heart after intravenous administration of Mn 2+ in order to compare to MnDPDP [10,11,28]. The normal heart rapidly uptakes Mn 2+ and it can be predicted that low flow regions of the heart would take up less Mn 2+ leading to an indicator of ischemia.…”

Section: Systemic Administration Of Mnmentioning

confidence: 99%

“…Indeed. MEMRI has been used to detect ischemia in both the intact and perfused rat and guinea pig heart [10,11,28]. Recently, this type of work was extended to the dog heart [42].…”

Section: Systemic Administration Of Mnmentioning

confidence: 99%

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Manganese Enhanced Magnetic Resonance Imaging

Lee¹,

Koretsky²

2004

CPB

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Abstract:Manganese is an essential metal that participates as a co-factor in a number of critical biological functions such as electron transport, detoxification of free radicals, and synthesis of neurotransmitters. Like other heavy metals, high concentrations of manganese are toxic. For example, chronic overexposure to manganese leads to movement disorders. In order to maintain this balance between being an essential participant in enzyme function and being a toxic heavy metal, a rich biology has evolved to transport and store manganese. Paramagnetic forms of manganese ions are potent MRI relaxation agents. Indeed, Mn 2+ was the first contrast agent proposed for use in MRI. Recently, there is renewed interest in combining the strong MRI relaxation effects of Mn 2+ with its unique biology in order to expand the range of information that can be measured by MRI. Manganese Enhanced MRI is being developed to give unique tissue contrast, assess tissue viability, act as a surrogate marker of calcium influx into cells and trace neuronal connections. In this article we review recent work and point out prospects for the future uses of manganese enhanced MRI.

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Relaxation enhancing properties of MnDPDP in human myocardium

Skjold

Vangberg

Kristoffersen

et al. 2004

Magnetic Resonance Imaging

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Purpose:To assess magnitude and duration of changes in myocardial longitudinal relaxation rate (R 1 ) in humans following infusion of the manganese (Mn) releasing contrast agent MnDPDP (Mn-dipyridoxyl-diphosphate). Materials and Methods:Fifteen healthy volunteers were divided into three groups. After initial myocardial and liver R 1 measurements using an inversion recovery (IR) turbo fast low-angle shot (FLASH) sequence at 1.5 Tesla, the groups were given different doses of intravenous MnDPDP: 5, 10 and 15 mol/kg body weight, respectively, over 30 minutes. R 1 measurements were then repeated at 1, 2, 4, 8, and 24 hours after the infusion ended. Results:The left ventricular wall R 1 prevalue was 0.98 second -1 (Ϯ0.04). R 1 increased on average (all 15 subjects) 0.41 second -1 (Ϯ0.09). The increase was present one hour after the end of the infusion, remained relatively constant the next two hours, and then declined gradually. After 24 hours, there was still a moderate R 1 elevation present, with an average R 1 -value of 1.16 (Ϯ0.05). There were only small differences in myocardial R 1 responses between the three doses investigated, which was contrasted by a marked dose-response in liver tissue. Conclusion:MnDPDP gave a significant and prolonged rise in myocardial R 1 even at a dose of 5 mol/kg. The R 1 -values in the myocardium did not increase linearly with higher doses. THE USE OF manganese-containing contrast agents in magnetic resonance imaging (MRI) for the study of the myocardium has been debated for several years. The background for this interest in manganese is that myocardial cells actively accumulate manganese ions (Mn 2ϩ ) through voltage-dependent slow calcium channels in the cell membrane (1-4). This has raised the question of whether intracellular manganese can be used as a contrast agent for MRI-based myocardial viability diagnosis.Thus far, several research groups have studied myocardial effects of manganese in MRI. Early studies showed that manganese contrast could be used to demarcate infarcted regions in animal hearts, first in excised hearts (5,6), and later on in images obtained with live animals (7-9). The accumulated manganese led to markedly increased longitudinal relaxation rates (R 1 ) in normal myocardium (3,8 -11). Theoretically, the relationship between the concentration of contrast agent in a tissue and the corresponding R 1 should be close to linear. Southon et al (11) demonstrated a steady increase in myocardial R 1 in pigs with intravenous doses of manganese dipyridoxyl diphosphate (MnDPDP) up to 20 mol/kg. Both Bremerich et al (8) and Wendland et al (9) found that R 1 -values increased with increasing doses of MnDPDP in rat myocardium. Both studies used doses of 25, 50, and 100 mol/kg, given over 1.5 and 3 minutes, respectively. Both showed an initial higher rise in R 1 in infarcted myocardium 5-10 minutes after the infusions than in normal myocardium. However, these initial high R 1 -values in infarcted myocardium decreased with time, while normal myocardium had a steady increa...

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Myocardial manganese elevation and proton relaxivity enhancement with manganese dipyridoxyl diphosphate. Ex vivo assessments in normally perfused and ischemic guinea pig hearts

Cited by 20 publications

References 0 publications

Manganese‐enhanced magnetic resonance imaging (MEMRI): methodological and practical considerations

Manganese‐enhanced magnetic resonance imaging (MEMRI): methodological and practical considerations

Manganese Enhanced Magnetic Resonance Imaging

Relaxation enhancing properties of MnDPDP in human myocardium

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