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

Silva, Afonso C.; Lee, Jun Young; Aoki, Ichio; Koretsky, Alan P.

doi:10.1002/nbm.945

Cited by 454 publications

(512 citation statements)

References 58 publications

(104 reference statements)

Supporting

Mentioning

487

Contrasting

Unclassified

Order By: Relevance

“…This design allows Mn 2+ to reach a stable distribution as previously published by others and our laboratory [28,29]. The period of stable distribution allows for reproducible and even distribution of signal during MRI [28][29][30][31][32][33][34]. For studies performed 2 days post-MPTP treatment, the first MnCl 2 was injected 4 h after MPTP/DPBS administration.…”

Section: Memrimentioning

confidence: 96%

Manganese-Enhanced Magnetic Resonance Imaging for Detection of Vasoactive Intestinal Peptide Receptor 2 Agonist Therapy in a Model of Parkinson's Disease

et al. 2016

View full text Add to dashboard Cite

Neuroprotective immunity is defined by transformation of T-cell polarity for therapeutic gain. For neurodegenerative disorders and specifically for Parkinson's disease (PD), granulocyte-macrophage colony stimulating factor or vasoactive intestinal peptide receptor 2 (VIPR2) agonists elicit robust anti-inflammatory microglial responses leading to neuronal sparing in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated mice. While neurotherapeutic potential was demonstrated for PD, there remain inherent limitations in translating these inventions from the laboratory to patients. One obstacle in translating such novel neurotherapeutics centers on the availability of suitable noninvasive methods to track disease progression and therapeutic efficacy. To this end, we developed manganese-enhanced magnetic resonance imaging (MEMRI) assays as a way to track a linkage between glial activation and VIPR2 agonist (LBT-3627)-induced neuroprotective immunity for MPTP-induced nigrostriatal degeneration. Notably, LBT-3627-treated, MPTP-intoxicated mice show reduced MEMRI brain signal intensities. These changes paralleled reduced astrogliosis and resulted in sparing of nigral tyrosine hydroxylase neurons. Most importantly, the data suggest that MEMRI can be developed as a biomarker tool to monitor neurotherapeutic responses that are relevant to common neurodegenerative disorders used to improve disease outcomes.

show abstract

Section: Memrimentioning

confidence: 96%

Manganese-Enhanced Magnetic Resonance Imaging for Detection of Vasoactive Intestinal Peptide Receptor 2 Agonist Therapy in a Model of Parkinson's Disease

et al. 2016

View full text Add to dashboard Cite

show abstract

“…12a). Sequential manganese-enhanced magnetic resonance imaging (MEMRI) 20 revealed hypointense lesions indicative of edema formation arising at 4-72h post-injection. At their peak, such lesions occupied up to 2.5% and 20% of the total cerebellar volume of wt and tga20 mice, respectively (Fig.…”

mentioning

confidence: 99%

The toxicity of antiprion antibodies is mediated by the flexible tail of the prion protein

Sonati

Reimann

Falsig

et al. 2013

Nature

195

289

View full text Add to dashboard Cite

Prion infections cause lethal neurodegeneration. This process requires the cellular prion protein (PrP(C); ref. 1), which contains a globular domain hinged to a long amino-proximal flexible tail. Here we describe rapid neurotoxicity in mice and cerebellar organotypic cultured slices exposed to ligands targeting the 1 and 3 helices of the PrP(C) globular domain. Ligands included seven distinct monoclonal antibodies, monovalent Fab1 fragments and recombinant single-chain variable fragment miniantibodies. Similar to prion infections, the toxicity of globular domain ligands required neuronal PrP(C), was exacerbated by PrP(C) overexpression, was associated with calpain activation and was antagonized by calpain inhibitors. Neurodegeneration was accompanied by a burst of reactive oxygen species, and was suppressed by antioxidants. Furthermore, genetic ablation of the superoxide-producing enzyme NOX2 (also known as CYBB) protected mice from globular domain ligand toxicity. We also found that neurotoxicity was prevented by deletions of the octapeptide repeats within the flexible tail. These deletions did not appreciably compromise globular domain antibody binding, suggesting that the flexible tail is required to transmit toxic signals that originate from the globular domain and trigger oxidative stress and calpain activation. Supporting this view, various octapeptide ligands were not only innocuous to both cerebellar organotypic cultured slices and mice, but also prevented the toxicity of globular domain ligands while not interfering with their binding. We conclude that PrP(C) consists of two functionally distinct modules, with the globular domain and the flexible tail exerting regulatory and executive functions, respectively. Octapeptide ligands also prolonged the life of mice expressing the toxic PrP(C) mutant, PrP(Δ94-134), indicating that the flexible tail mediates toxicity in two distinct PrP(C)-related conditions. Flexible tail-mediated toxicity may conceivably play a role in further prion pathologies, such as familial Creutzfeldt-Jakob disease in humans bearing supernumerary octapeptides. (Fig. 1b). None of three high-affinity antibodies to the octapeptide repeats (OR, residues 50-90 embedded within the FT) were neurotoxic (Fig. 1b). Antibodies POM3 and D13, which bind the "charged cluster-2" 11 (CC2, residues 95-110), were innocuous at 67 nM but neurotoxic at 200 nM (Fig. 1b). None of the tested antibodies were toxic to Prnp o/o COCS ( Supplementary Fig. 2a). The identity of the targeted epitopes appeared to be a better predictor of PrP C antibody toxicity than their affinity to PrP C , suggesting that neurotoxicity resulted from the interaction of antibodies with specific PrP C domains (Supplementary Table 2).The mechanisms of neurotoxicity were further explored using POM1, a highly toxic antibody targeting the GD. Wild-type (wt) and tga20 COCS lost most granule cells (CGC) within 28 and 14 days post-exposure (dpe) to POM1, respectively (Fig. 2a-c). Controls included POM1-treated Prnp o/o COCS 12 , t...

show abstract

“…the visual cortex, superior colliculus and flocculus-parafloccular complex (FL-PFL) of the vestibulocerebellum. The flashing frequencies that evoked the maximum BOLD response turned out to be low (1)(2)(3)(4)(5) for the visual cortex and FL-PFL, whereas the superior colliculus responded optimally to high flashing rates (8)(9)(10)(11)(12). These correlations between frequencydependent responses of different visual areas suggested a functional relationship between the visual cortex and FL-PFL rather than between the superior colliculus and FL-PFL.…”

Section: Fmri Applications Fmri Studies Of Somatosensory Neuronal Cirmentioning

confidence: 94%

“…In the past, this was achieved with invasive blood sampling for repetitive blood gas analysis throughout the fMRI experiment. The drawbacks of limited blood sample availability and blindness to pCO 2 fluctuations between sampling periods have now been eliminated by using the continuous and non-invasive recording of transcutaneous pCO 2 (23,30,37,38) or end-tidal pCO 2 values with MRI-compatible capnometry in intubated animals (39)(40)(41) or simply with an inhalation mask (42) for which linear correlations with arterial pCO 2 have been established (43).…”

Section: Physiological Monitoringmentioning

confidence: 99%

“…Yet, in small animal research, Mn 2þ as a paramagnetic Ca 2þ analogue provides information on the level of electrical activity in the brain, as its neuronal uptake is dependent on electrical activity. The Mn 2þ ion has become one of the most powerful and promising positive contrast agents; it covers a broad spectrum of functional and anatomical applications and is a powerful tool for studying functional brain activation [for reviews, see the special issue of NMR in Biomedicine (2)]. fMRI in small animals offer other advantages: they provide appropriate biophysical models allowing: (a) a better interpretation of the contrast in the functional MR images; (b) the creation of new forms of contrast [using intravascular agents to provide CBV and CBF measurements and manganese-enhanced MRI (MEMRI) as outlined above]; (c) an improved design of fMRI techniques per se (e.g.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Current status of functional MRI on small animals: application to physiology, pathophysiology, and cognition

et al. 2007

View full text Add to dashboard Cite

This review aims to make the reader aware of the potential of functional MRI (fMRI) in brain activation studies in small animal models. As small animals generally require anaesthesia for immobilization during MRI protocols, this is believed to be a serious limitation to the type of question that can be addressed with fMRI. We intend to introduce a fresh view with an in-depth overview of the surprising number of fMRI applications in a wide range of important research domains in neuroscience. These include the pathophysiology of brain functioning, the basic science of activity, and functional connectivity of different sensory circuits, including sensory brain mapping, the challenges when studying the hypothalamus as the major control centre in the central nervous system, and the limbic system as neural substrate for emotions and reward. Finally the contribution of small animal fMRI research to cognitive neuroscience is outlined. This review avoids focusing exclusively on traditional small laboratory animals such as rodents, but rather aims to broaden the scope by introducing alternative lissencephalic animal models such as songbirds and fish, as these are not yet well recognized as neuroimaging study subjects. These models are well established in many other neuroscience disciplines, and this review will show that their investigation with in vivo imaging tools will open new doors to cognitive neuroscience and the study of the autonomous nervous system in experimental animals.

show abstract

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

Cited by 454 publications

References 58 publications

Manganese-Enhanced Magnetic Resonance Imaging for Detection of Vasoactive Intestinal Peptide Receptor 2 Agonist Therapy in a Model of Parkinson's Disease

Manganese-Enhanced Magnetic Resonance Imaging for Detection of Vasoactive Intestinal Peptide Receptor 2 Agonist Therapy in a Model of Parkinson's Disease

The toxicity of antiprion antibodies is mediated by the flexible tail of the prion protein

Current status of functional MRI on small animals: application to physiology, pathophysiology, and cognition

Contact Info

Product

Resources

About