Combined off‐resonance imaging and T2 relaxation in the rotating frame for positive contrast MR imaging of infection in a murine burn model

Andronesi, Ovidiu C.; Mintzopoulos, Dionyssios; Psychogios, Nikolaos; Kesarwani, Meenu; He, Jianxin; Yasuhara, Shingo; Dai, George; Rahme, Laurence G.; Tzika, A. Aria

doi:10.1002/jmri.22349

Cited by 13 publications

(16 citation statements)

References 59 publications

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“…MRI of ultrasmall particles of iron oxide (USPIO) contrast agents has been used to study phagocyte recruitment in an arthritis model , Pseudomonas aeruginosa in a burn model , osteomyelitis , toxoplasmosis in brain and Staphylococcus aureus in soft tissue . MRI with USPIO contrast agents has been used in kidneys for the detection of allograft rejection and inflammation following ischemia .…”

Section: Introductionmentioning

confidence: 99%

MRI confirms loss of blood–brain barrier integrity in a mouse model of disseminated candidiasis

et al. 2013

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Disseminated candidiasis primarily targets the kidneys and brain in mice and humans. Damage to these critical organs leads to the high mortality associated with such infections, and invasion across the blood- brain barrier can result in fungal meningoencephalitis. Candida albicans can penetrate a brain endothelial cell barrier in vitro through transcellular migration, but this mechanism has not been confirmed in vivo. MRI imaging using the extracellular vascular contrast agent Gd-DTPA demonstrated that integrity of the blood- brain barrier is lost during C. albicans invasion. Intravital two-photon laser scanning microscopy was used to provide the first real time demonstration of C. albicans colonizing the living brain, where both yeast and filamentous forms of the pathogen were found. Furthermore, we adapted a previously described method utilizing MRI to monitor inflammatory cell recruitment into infected tissues in mice. Macrophages and other phagocytes were visualized in kidney and brain by administering ultra-small iron oxide particles. In addition to obtaining new insights into the passage of C. albicans across brain microvasculature, these imaging methods provide useful tools to further study the pathogenesis of C. albicans infections, define the roles of Candida virulence genes in kidney versus brain infection, and assess new therapeutic measures for drug development.

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Section: Introductionmentioning

confidence: 99%

MRI confirms loss of blood–brain barrier integrity in a mouse model of disseminated candidiasis

et al. 2013

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“…This offset resonance peak could be exploited for producing a signal that is distinct from water. This has the advantage of eliminating background interference and can be used in conjunction with conventional T 2 ‐weighted imaging to achieve dual‐contrast enhancement effects 17. Of greater significance is that the MFNCs could be well‐dispersed in aqueous media with excellent colloidal stability due to their amphiphilic nature, making it potentially useful for in vivo biological applications.…”

Section: Introductionmentioning

confidence: 99%

Superparamagnetic Nanostructures for Off‐Resonance Magnetic Resonance Spectroscopic Imaging

Choo

Peng

Rajendran

et al. 2012

Adv Funct Materials

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This study proposes a new method to generate positive contrast in magnetic resonance imaging (MRI) using superparamagnetic contrast agents. Superparamagnetic nanostructures consisting of octahedron manganese ferrite nanoparticles embedded in spherical nanogels are fabricated using a bottom‐up approach. The composite nanoparticles are strongly magnetized in an external magnetic field and produce a unique NMR frequency shift in water protons, which can be demonstrated in MR spectroscopy and imaging to be different from the bulk pool. Moreover, the particles exhibit excellent colloidal stability in aqueous media and good cell biocompatibility. Hence, these particles are potentially useful as biomarkers by taking advantage of the positive contrast effects produced in MRI.

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“…Here, we employed a T2* weighting imaging method because our agent is a T2* susceptibility agent. We used supermaramgentic iron nanoparticles, a T2* susceptibility agent, as used by us before [27], which typically produces effective T2* relaxation (in gradient echo based sequences) typically an order of magnitude higher for nanoparticles compared to that of Gadolinium complexes. This is partially due to the higher dipolar R2 relaxivity of these agents, but also due to their much higher magnetization at clinical fields.…”

Section: Discussionmentioning

confidence: 99%

“…As evident from our results, we constantly observe a higher signal from the burned site than the control and this is also depicted in the cumulative results. This is mainly due to the unique advantages of our positive contrast methodology [27] that enhances the anatomical features and allows for functional molecular imaging of the mouse. Furthermore it is important to notice that the contrast agent is not administered locally but rather systematically, so the differences in the contrast is due to its self-accumulation and self-targeting to the burn site that allows for easy and accurate detection and imaging.…”

Section: Discussionmentioning

confidence: 99%

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Imaging C-Fos Gene Expression in Burns Using Lipid Coated Spion Nanoparticles

Papagiannaros¹,

Righi²,

Day³

et al. 2012

AMI

Self Cite

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MR imaging of gene transcription is important as it should enable the non-invasive detection of mRNA alterations in disease. A range of MRI methods have been proposed for in vivo molecular imaging of cells based on the use of ultra-small super-paramagnetic iron oxide (USPIO) nanoparticles and related susceptibility weighted imaging methods. Although immunohistochemistry can robustly differentiate the expression of protein variants, there is currently no direct gene assay technique that is capable of differentiating established to differentiate the induction profiles of c-Fos mRNA in vivo. To visualize the differential FosB gene expression profile in vivo after burn trauma, we developed MR probes that link the T2* contrast agent [superparamagnetic iron oxide nanoparticles (SPION)] with an oligodeoxynucleotide (ODN) sequence complementary to FosB mRNA to visualize endogenous mRNA targets via in vivo hybridization. The presence of this SPION-ODN probe in cells results in localized signal reduction in T2*-weighted MR images, in which the rate of signal reduction (R2*) reflects the regional iron concentration at different stages of amphetamine (AMPH) exposure in living mouse tissue. Our aim was to produce a superior contrast agent that can be administered using systemic as opposed to local administration and which will target and accumulate at sites of burn injury. Specifically, we developed and evaluated a PEGylated lipid coated MR probe with ultra-small super-paramagnetic iron oxide nanoparticles (USPION, a T2 susceptibility agent) coated with cationic fusogenic lipids, used for cell transfection and gene delivery and covalently linked to a phosphorothioate modified oligodeoxynucleotide (sODN) complementary to c-Fos mRNA (SPION-cFos) and used the agent to image mice with leg burns. Our study demonstrated the feasibility of monitoring burn injury using MR imaging of c-Fos transcription in vivo, in a clinically relevant mouse model of burn injury for the first time.

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Combined off‐resonance imaging and T2 relaxation in the rotating frame for positive contrast MR imaging of infection in a murine burn model

Cited by 13 publications

References 59 publications

MRI confirms loss of blood–brain barrier integrity in a mouse model of disseminated candidiasis

MRI confirms loss of blood–brain barrier integrity in a mouse model of disseminated candidiasis

Superparamagnetic Nanostructures for Off‐Resonance Magnetic Resonance Spectroscopic Imaging

Imaging C-Fos Gene Expression in Burns Using Lipid Coated Spion Nanoparticles

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