scholarly journals Biocompatibility of Bacterial Magnetosomes as MRI Contrast Agent: A Long-Term In Vivo Follow-Up Study

Nanomaterials ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1235
Author(s):  
Xiaohui Nan ◽  
Wenjia Lai ◽  
Dan Li ◽  
Jiesheng Tian ◽  
Zhiyuan Hu ◽  
...  

Derived from magnetotactic bacteria (MTB), magnetosomes consist of magnetite crystals enclosed within a lipid bilayer membrane and are known to possess advantages over artificially synthesized nanoparticles because of the narrow size distribution, uniform morphology, high purity and crystallinity, single magnetic domain, good biocompatibility, and easy surface modification. These unique properties have increasingly attracted researchers to apply bacterial magnetosomes (BMs) in the fields of biology and medicine as MRI imaging contrast agents. Due to the concern of biosafety, a long-term follow-up of the distribution and clearance of BMs after entering the body is necessary. In this study, we tracked changes of BMs in major organs of mice up to 135 days after intravenous injection using a combination of several techniques. We not only confirmed the liver as the well-known targeted organs of BMs, but also found that BMs accumulated in the spleen. Besides, two major elimination paths, as well as the approximate length of time for BMs to be cleared from the mice, were revealed. Together, the results not only confirm that BMs have high biocompatibility, but also provide a long-term in-vivo assessment which may further help to forward the clinical applications of BMs as an MRI contrast agent.

2021 ◽  
Vol 11 (3) ◽  
pp. 1165
Author(s):  
Wen-Tien Hsiao ◽  
Yi-Hong Chou ◽  
Jhong-Wei Tu ◽  
Ai-Yih Wang ◽  
Lu-Han Lai

The purpose of this study is to establish the minimal injection doses of magnetic resonance imaging (MRI) contrast agents that can achieve optimized images while improving the safety of injectable MRI drugs. Gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA) and ferucarbotran, commonly used in clinical practice, were selected and evaluated with in vitro and in vivo experiments. MRI was acquired using T1-weighted (T1W) and T2-weighted (T2W) sequences, and the results were quantitatively analyzed. For in vitro experiments, results showed that T1W and T2W images were optimal when Gd-DTPA-bisamide (2-oxoethyl) (Gd-DTPA-BMEA) and ferucarbotran were diluted to a volume percentage of 0.6% and 0.05%; all comparisons were significant differences in grayscale statistics using one-way analysis of variance (ANOVA). For in vivo experiments, the contrast agent with optimal concentration percentages determined from in vitro experiments were injected into mice with an injection volume of 100 μL, and the images of brain, heart, liver, and mesentery before and after injection were compared. The statistical results showed that the p values of both T1W and T2W were less than 0.001, which were statistically significant. Under safety considerations for MRI contrast agent injection, optimized MRI images could still be obtained after reducing the injection concentration, which can provide a reference for the safety concentrations of MRI contrast agent injection in the future.


F1000Research ◽  
2014 ◽  
Vol 2 ◽  
pp. 252
Author(s):  
Rachael A Panizzo ◽  
David G Gadian ◽  
Jane C Sowden ◽  
Jack A Wells ◽  
Mark F Lythgoe ◽  
...  

Efficacy of neural stem/progenitor cell (NPC) therapies after cerebral ischaemia could be better evaluated by monitoring in vivo migration and distribution of cells post-engraftment in parallel with analysis of lesion volume and functional recovery. Magnetic resonance imaging (MRI) is ideally placed to achieve this, but still poses several challenges. We show that combining the ferumoxide MRI contrast agent Endorem with protamine sulphate (FePro) improves iron oxide uptake in cells compared to Endorem alone and is non-toxic. Hence FePro complex is a better contrast agent than Endorem for monitoring NPCs. FePro complex-labelled NPCs proliferated and differentiated normally in vitro, and upon grafting into the brain 48 hours post-ischaemia they were detected in vivo by MRI. Imaging over four weeks showed the development of a confounding endogenous hypointense contrast evolution at later timepoints within the lesioned tissue. This was at least partly due to accumulation within the lesion of macrophages and endogenous iron. Neither significant NPC migration, assessed by MRI and histologically, nor a reduction in the ischaemic lesion volume was observed in NPC-grafted brains.  Crucially, while MRI provides reliable information on engrafted cell location early after an ischaemic insult, pathophysiological changes to ischaemic lesions can interfere with cellular imaging at later timepoints.


2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Rami Tadros ◽  
Bhakti Rawal ◽  
Karen Briley-Saebo ◽  
David O’Connor ◽  
Dan Han ◽  
...  

Introduction: Mesenchymal stem cells (MSC) are being investigated in porcine abdominal aortic aneurysm (PAAA) models for their repair potential. This study uses MSCs labeled with the MRI contrast agent Ferex to non-invasively evaluate MSC migration in-vivo. Methods: MSCs from 6 pigs were isolated from bone marrow via Ficoll Paque separation and expanded in culture. Using a Lentiviral vector, MSC from all 6 pigs were transfected with green florescent protein (GFP). MSCs from 4 of these pigs were also labeled with 200μg/ml Ferex using Poly-L-Lysine and then analyzed for Ferex uptake and viability. Preservation of the MSC phenotype was confirmed using flow cytometry by detecting positive CD90 and negative CD45 and CD117. Transmission electron microscopy established that Ferex localized to lysosomes. MSCs were then injected into the adventitia of the PAAA. In-vivo MRI was performed using multiple echo gradient echo sequences. Effective transverse relaxation times (T2* values) were calculated on a pixel-by-pixel basis as a function of time post cell transplantation. Results: Ferex labeled MSCs were visible post transplantation at 4, 11, 15 and 21 days using MRI. The MRI signal void (decreased T2* values) correlated with the presence of Ferex within the PAAA. This signal loss progressively expanded circumferentially at each study interval representing cellular movement. MSC migration and localization were confirmed with GFP visualization on fluorescence microscopy and immunohistochemistry. In-vivo MRI signals also correlate with iron deposition on Perl’s stain. Conclusion: Ferex can be used as an in-vivo tracking agent of MSCs in PAAA models.


2012 ◽  
Vol 70 (4) ◽  
pp. 1016-1025 ◽  
Author(s):  
Nevin McVicar ◽  
Alex X. Li ◽  
Mojmír Suchý ◽  
Robert H. E. Hudson ◽  
Ravi S. Menon ◽  
...  

2014 ◽  
Vol 2 (20) ◽  
pp. 3041 ◽  
Author(s):  
Yueer Yan ◽  
Erlei Shao ◽  
Xiaoyong Deng ◽  
Jiahui Liu ◽  
Yahong Zhang ◽  
...  

2011 ◽  
Vol 8 (5) ◽  
pp. 1750-1756 ◽  
Author(s):  
Valeria Menchise ◽  
Giuseppe Digilio ◽  
Eliana Gianolio ◽  
Evelina Cittadino ◽  
Valeria Catanzaro ◽  
...  

2004 ◽  
Vol 14 (11) ◽  
pp. 2787-2790 ◽  
Author(s):  
Tatsuhiro Yamamoto ◽  
Kenjiro Ikuta ◽  
Keiji Oi ◽  
Kohtaro Abe ◽  
Toyokazu Uwatoku ◽  
...  

2015 ◽  
Vol 112 (21) ◽  
pp. 6607-6612 ◽  
Author(s):  
Shenghui Xue ◽  
Hua Yang ◽  
Jingjuan Qiao ◽  
Fan Pu ◽  
Jie Jiang ◽  
...  

With available MRI techniques, primary and metastatic liver cancers that are associated with high mortality rates and poor treatment responses are only diagnosed at late stages, due to the lack of highly sensitive contrast agents without Gd3+ toxicity. We have developed a protein contrast agent (ProCA32) that exhibits high stability for Gd3+ and a 1011-fold greater selectivity for Gd3+ over Zn2+ compared with existing contrast agents. ProCA32, modified from parvalbumin, possesses high relaxivities (r1/r2: 66.8 mmol−1⋅s−1/89.2 mmol−1⋅s−1 per particle). Using T1- and T2-weighted, as well as T2/T1 ratio imaging, we have achieved, for the first time (to our knowledge), robust MRI detection of early liver metastases as small as ∼0.24 mm in diameter, much smaller than the current detection limit of 10–20 mm. Furthermore, ProCA32 exhibits appropriate in vivo preference for liver sinusoidal spaces and pharmacokinetics for high-quality imaging. ProCA32 will be invaluable for noninvasive early detection of primary and metastatic liver cancers as well as for monitoring treatment and guiding therapeutic interventions, including drug delivery.


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