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Nuclear Microscopy: A Novel Technique for Quantitative Imaging of Gadolinium Distribution within Tissue Sections

Published online by Cambridge University Press:  03 July 2009

Reshmi Rajendran ,
John A. Ronald ,
Tao Ye ,
Ren Minqin ,
John W. Chen ,
Ralph Weissleder ,
Brian K. Rutt ,
Barry Halliwell  and
Frank Watt
Reshmi Rajendran*
Affiliation:
Centre for Ion Beam Applications, Department of Physics, National University of Singapore, Singapore
John A. Ronald
Affiliation:
Robarts Research Institute, University of Western Ontario, London, Ontario, Canada
Tao Ye
Affiliation:
Centre for Ion Beam Applications, Department of Physics, National University of Singapore, Singapore
Ren Minqin
Affiliation:
Centre for Ion Beam Applications, Department of Physics, National University of Singapore, Singapore
John W. Chen
Affiliation:
Center for Molecular Imaging Research, Department of Radiology, Massachusetts General Hospital, Boston, MA, USA
Ralph Weissleder
Affiliation:
Center for Molecular Imaging Research, Department of Radiology, Massachusetts General Hospital, Boston, MA, USA
Brian K. Rutt
Affiliation:
Robarts Research Institute, University of Western Ontario, London, Ontario, Canada
Barry Halliwell
Affiliation:
Department of Biochemistry, National University of Singapore, Singapore
Frank Watt
Affiliation:
Centre for Ion Beam Applications, Department of Physics, National University of Singapore, Singapore
*
Corresponding author. E-mail: [email protected]
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Abstract

All clinically-approved and many novel gadolinium (Gd)-based contrast agents used to enhance signal intensity in magnetic resonance imaging (MRI) are optically silent. To verify MRI results, a “gold standard” that can map and quantify Gd down to the parts per million (ppm) levels is required. Nuclear microscopy is a relatively new technique that has this capability and is composed of a combination of three ion beam techniques: scanning transmission ion microscopy, Rutherford backscattering spectrometry, and particle induced X-ray emission used in conjunction with a high energy proton microprobe. In this proof-of-concept study, we show that in diseased aortic vessel walls obtained at 2 and 4 h after intravenous injection of the myeloperoxidase-senstitive MRI agent, bis-5-hydroxytryptamide-diethylenetriamine-pentaacetate gadolinium, there was a time-dependant Gd clearance (2 h = 18.86 ppm, 4 h = 8.65 ppm). As expected, the control animal, injected with the clinically-approved conventional agent diethylenetriamine-pentaacetate gadolinium and sacrificed 1 week after injection, revealed no significant residual Gd in the tissue. Similar to known in vivo Gd pharmacokinetics, we found that Gd concentration dropped by a factor of 2 in vessel wall tissue in 1.64 h. Further high-resolution studies revealed that Gd was relatively uniformly distributed, consistent with random agent diffusion. We conclude that nuclear microscopy is potentially very useful for validation studies involving Gd-based magnetic resonance contrast agents.

Keywords

gadoliniummagnetic resonance imagingnuclear microscopyPIXESTIMRBSatherosclerosis
Type
Biological Applications
Information
Microscopy and Microanalysis , Volume 15 , Issue 4 , August 2009 , pp. 338 - 344
Copyright
Copyright © Microscopy Society of America 2009

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