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In vivo multicolor molecular MR imaging using diamagnetic chemical exchange saturation transfer liposomes.

ABSTRACT: A variety of (super)paramagnetic contrast agents are available for enhanced MR visualization of specific tissues, cells, or molecules. To develop alternative contrast agents without the presence of metal ions, liposomes were developed containing simple bioorganic and biodegradable compounds that produce diamagnetic chemical exchange saturation transfer MR contrast. This diamagnetic chemical exchange saturation transfer contrast is frequency-dependent, allowing the unique generation of "multicolor" images. The contrast can be turned on and off at will, and standard images do not show the presence of these agents. As an example, glycogen, L-arginine, and poly-L-lysine were encapsulated inside liposomes and injected intradermally into mice to image the lymphatic uptake of these liposomes. Using a frequency-dependent acquisition scheme, it is demonstrated that multicolor MRI can differentiate between different contrast particles in vivo following their homing to draining lymph nodes. Being nonmetallic and bioorganic, these diamagnetic chemical exchange saturation transfer liposomes form an attractive novel platform for multicolor imaging in vivo.

SUBMITTER: Liu G

PROVIDER: S-EPMC3522097 | biostudies-other | 2012 Apr

REPOSITORIES: biostudies-other

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In vivo multicolor molecular MR imaging using diamagnetic chemical exchange saturation transfer liposomes.

Liu Guanshu G Moake Matthew M Har-el Yah-el YE Long Chris M CM Chan Kannie W Y KW Cardona Amanda A Jamil Muksit M Walczak Piotr P Gilad Assaf A AA Sgouros George G van Zijl Peter C M PC Bulte Jeff W M JW McMahon Michael T MT

Magnetic resonance in medicine 20110823 4

A variety of (super)paramagnetic contrast agents are available for enhanced MR visualization of specific tissues, cells, or molecules. To develop alternative contrast agents without the presence of metal ions, liposomes were developed containing simple bioorganic and biodegradable compounds that produce diamagnetic chemical exchange saturation transfer MR contrast. This diamagnetic chemical exchange saturation transfer contrast is frequency-dependent, allowing the unique generation of "multicolo ...[more]

PMID: 22392814

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Project description:An improved pre-clinical cardiac chemical exchange saturation transfer (CEST) pulse sequence (cardioCEST) was used to selectively visualize paramagnetic CEST (paraCEST)-labeled cells following intramyocardial implantation. In addition, cardioCEST was used to examine the effect of diet-induced obesity upon myocardial creatine CEST contrast. CEST pulse sequences were designed from standard turbo-spin-echo and gradient-echo sequences, and a cardiorespiratory-gated steady-state cine gradient-echo sequence. In vitro validation studies performed in phantoms composed of 20 mM Eu-HPDO3A, 20 mM Yb-HPDO3A, or saline demonstrated similar CEST contrast by spin-echo and gradient-echo pulse sequences. Skeletal myoblast cells (C2C12) were labeled with either Eu-HPDO3A or saline using a hypotonic swelling procedure and implanted into the myocardium of C57B6/J mice. Inductively coupled plasma mass spectrometry confirmed cellular levels of Eu of 2.1 × 10(-3) ng/cell in Eu-HPDO3A-labeled cells and 2.3 × 10(-5) ng/cell in saline-labeled cells. In vivo cardioCEST imaging of labeled cells at ±15 ppm was performed 24 h after implantation and revealed significantly elevated asymmetric magnetization transfer ratio values in regions of Eu-HPDO3A-labeled cells when compared with surrounding myocardium or saline-labeled cells. We further utilized the cardioCEST pulse sequence to examine changes in myocardial creatine in response to diet-induced obesity by acquiring pairs of cardioCEST images at ±1.8 ppm. While ventricular geometry and function were unchanged between mice fed either a high-fat diet or a corresponding control low-fat diet for 14 weeks, myocardial creatine CEST contrast was significantly reduced in mice fed the high-fat diet. The selective visualization of paraCEST-labeled cells using cardioCEST imaging can enable investigation of cell fate processes in cardioregenerative medicine, or multiplex imaging of cell survival with imaging of cardiac structure and function and additional imaging of myocardial creatine.

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In vivo multicolor molecular MR imaging using diamagnetic chemical exchange saturation transfer liposomes.

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In vivo multicolor molecular MR imaging using diamagnetic chemical exchange saturation transfer liposomes.

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