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>3.0.co;2-z

Cited by 35 publications

(13 citation statements)

References 34 publications

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“…The iron-oxide-labeled cells remain observable for longer than those labeled with Mn[19], [20]. On the other hand, Mn 2+ has been proposed as a cell viability indicator for cardiac applications because Mn only accumulates in living cells[35], [46]. In addition, (depending on the concentration) Mn 2+ mainly positively enhances the exact site of the transplanted cells without image distortion due to susceptibility differences in T 1 -weighted MRI.…”

Section: Discussionmentioning

confidence: 99%

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In Vivo Tracking of Transplanted Mononuclear Cells Using Manganese-Enhanced Magnetic Resonance Imaging (MEMRI)

Odaka¹,

Aoki²,

Moriya

et al. 2011

PLoS ONE

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BackgroundTransplantation of mononuclear cells (MNCs) has previously been tested as a method to induce therapeutic angiogenesis to treat limb ischemia in clinical trials. Non-invasive high resolution imaging is required to track the cells and evaluate clinical relevance after cell transplantation. The hypothesis that MRI can provide in vivo detection and long-term observation of MNCs labeled with manganese contrast-agent was investigated in ischemic rat legs.Methods and FindingsThe Mn-labeled MNCs were evaluated using 7-tesla high-field magnetic resonance imaging (MRI). Intramuscular transplanted Mn-labeled MNCs were visualized with MRI for at least 7 and up to 21 days after transplantation in the ischemic leg. The distribution of Mn-labeled MNCs was similar to that of 111In-labeled MNCs measured with single-photon emission computed tomography (SPECT) and DiI-dyed MNCs with fluorescence microscopy. In addition, at 1–2 days after transplantation the volume of the site injected with intact Mn-labeled MNCs was significantly larger than that injected with dead MNCs, although the dead Mn-labeled MNCs were also found for approximately 2 weeks in the ischemic legs. The area covered by CD31-positive cells (as a marker of capillary endothelial cells) in the intact Mn-MNCs implanted site at 43 days was significantly larger than that at a site implanted with dead Mn-MNCs.ConclusionsThe present Mn-enhanced MRI method enabled visualization of the transplanted area with a 150–175 µm in-plane spatial resolution and allowed the migration of labeled-MNCs to be observed for long periods in the same subject. After further optimization, MRI-based Mn-enhanced cell-tracking could be a useful technique for evaluation of cell therapy both in research and clinical applications.

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Section: Discussionmentioning

confidence: 99%

“…The fact that Mn 2+ can enter properly functioning cells has led to work aimed at developing Mn 2+ or Mn-dipyridoxyl-diphosphate (Mn-DPDP) as cell viability indicators for cardiac applications[35]. Mn 2+ has also been applied to immunocyte labeling in vitro and the toxicity, immunoreactivity, and relaxivity for MRI have been tested[36].…”

Section: Introductionmentioning

confidence: 99%

In Vivo Tracking of Transplanted Mononuclear Cells Using Manganese-Enhanced Magnetic Resonance Imaging (MEMRI)

Odaka¹,

Aoki²,

Moriya

et al. 2011

PLoS ONE

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“…Mn toxicity has been identified through overexposure of Mn in occupational (e.g., welders and smelters), environmental, medical and dietary routes [6,8,12]. It has been noted that Mn causes toxic effect mainly in the CNS and lungs, as well as in heart, liver, and reproductive organs and during embryonic stage [4,7,13,14,15,16,17,18,19,20,21]. Some countries use anti-knock agent methylcyclopentadienyl manganese tricarbonyl as a fuel additive, which could increase Mn overexposure to human [22,23].…”

Section: Introductionmentioning

confidence: 99%

Polyphenolic Extract of Euphorbia supina Attenuates Manganese-Induced Neurotoxicity by Enhancing Antioxidant Activity through Regulation of ER Stress and ER Stress-Mediated Apoptosis

Bahar

Lee

Bhattarai

et al. 2017

IJMS

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Manganese (Mn) is an important trace element present in human body, which acts as an enzyme co-factor or activator in various metabolic reactions. While essential in trace amounts, excess levels of Mn in human brain can produce neurotoxicity, including idiopathic Parkinson’s disease (PD)-like extrapyramidal manganism symptoms. This study aimed to investigate the protective role of polyphenolic extract of Euphorbia supina (PPEES) on Mn-induced neurotoxicity and the underlying mechanism in human neuroblastoma SKNMC cells and Sprague-Dawley (SD) male rat brain. PPEES possessed significant amount of total phenolic and flavonoid contents. PPEES also showed significant antioxidant activity in 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging and reducing power capacity (RPC) assays. Our results showed that Mn treatment significantly reduced cell viability and increased lactate dehydrogenase (LDH) level, which was attenuated by PPEES pretreatment at 100 and 200 µg/mL. Additionally, PPEES pretreatment markedly attenuated Mn-induced antioxidant status alteration by resolving the ROS, MDA and GSH levels and SOD and CAT activities. PPEES pretreatment also significantly attenuated Mn-induced mitochondrial membrane potential (ΔΨm) and apoptosis. Meanwhile, PPEES pretreatment significantly reversed the Mn-induced alteration in the GRP78, GADD34, XBP-1, CHOP, Bcl-2, Bax and caspase-3 activities. Furthermore, administration of PPEES (100 and 200 mg/kg) to Mn exposed rats showed improvement of histopathological alteration in comparison to Mn-treated rats. Moreover, administration of PPEES to Mn exposed rats showed significant reduction of 8-OHdG and Bax immunoreactivity. The results suggest that PPEES treatment reduces Mn-induced oxidative stress and neuronal cell loss in SKNMC cells and in the rat brain. Therefore, PPEES may be considered as potential treat-ment in Mn-intoxicated patients.

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“…Unlike gadolinium, a paramagnetic lanthanide ion approved for clinical use, manganese is an endogenous constituent and behaves like a calcium ion analogue that often acts as a regulatory cofactor in a number of important enzymes and receptors [3]. Its unique biological properties have lent themselves to various applications in functional and molecular imaging, most notably in imaging the liver [4], brain function [5], myocardial viability [6], and, more recently, cancer cells [7], [8]. In virtually all applications, the standard protocol is a T 1 -weighted pulse sequence to obtain positive signal contrast in areas of Mn accumulation.…”

Section: Introductionmentioning

confidence: 99%

Ultrashort Echo Time for Improved Positive-Contrast Manganese-Enhanced MRI of Cancer

Nofiele

Cheng

2013

PLoS ONE

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ObjectiveManganese (Mn) is a positive magnetic resonance imaging (MRI) contrast agent that has been used to obtain physiological, biochemical, and molecular biological information. There is great interest to broaden its applications, but a major challenge is to increase detection sensitivity. Another challenge is distinguishing regions of Mn-related signal enhancement from background tissue with inherently similar contrast. To overcome these limitations, this study investigates the use of ultrashort echo time (UTE) and subtraction UTE (SubUTE) imaging for more sensitive and specific determination of Mn accumulation.Materials and MethodsSimulations were performed to investigate the feasibility of UTE and SubUTE for Mn-enhanced MRI and to optimize imaging parameters. Phantoms containing aqueous Mn solutions were imaged on a MRI scanner to validate simulations predictions. Breast cancer cells that are very aggressive (MDA-MB-231 and a more aggressive variant LM2) and a less aggressive cell line (MCF7) were labeled with Mn and imaged on MRI. All imaging was performed on a 3 Tesla scanner and compared UTE and SubUTE against conventional T 1-weighted spoiled gradient echo (SPGR) imaging.ResultsSimulations and phantom imaging demonstrated that UTE and SubUTE provided sustained and linearly increasing positive contrast over a wide range of Mn concentrations, whereas conventional SPGR displayed signal plateau and eventual decrease. Higher flip angles are optimal for imaging higher Mn concentrations. Breast cancer cell imaging demonstrated that UTE and SubUTE provided high sensitivity, with SubUTE providing background suppression for improved specificity and eliminating the need for a pre-contrast baseline image. The SubUTE sequence allowed the best distinction of aggressive breast cancer cells.ConclusionsUTE and SubUTE allow more sensitive and specific positive-contrast detection of Mn enhancement. This imaging capability can potentially open many new doors for Mn-enhanced MRI in vascular, cellular, and molecular imaging.

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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 35 publications

References 34 publications

In Vivo Tracking of Transplanted Mononuclear Cells Using Manganese-Enhanced Magnetic Resonance Imaging (MEMRI)

In Vivo Tracking of Transplanted Mononuclear Cells Using Manganese-Enhanced Magnetic Resonance Imaging (MEMRI)

Polyphenolic Extract of Euphorbia supina Attenuates Manganese-Induced Neurotoxicity by Enhancing Antioxidant Activity through Regulation of ER Stress and ER Stress-Mediated Apoptosis

Ultrashort Echo Time for Improved Positive-Contrast Manganese-Enhanced MRI of Cancer

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