Nuclear microscopy: a novel technique for quantitative imaging of gadolinium distribution within tissue sections.
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-sensitive 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.
Rajendran
Reshmi
R
Centre for Ion Beam Applications, Department of Physics, National University of Singapore, Singapore. reshmi_rajendran@sbic.a-star.edu.sg
Ronald
John A
JA
Ye
Tao
T
Minqin
Ren
R
Chen
John W
JW
Weissleder
Ralph
R
Rutt
Brian K
BK
Halliwell
Barry
B
Watt
Frank
F
D000818:Animals; D001011:Aorta / Q000737:chemistry*; D005682:Gadolinium / Q000008:administration & dosage / Q000032:analysis* / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008853:Microscopy / Q000379:methods*; D010336:Pathology / Q000379:methods*; D011817:Rabbits; D013997:Time Factors
D005682:Gadolinium