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Dysprosium-bearing red cells as potential transverse relaxation agents for MRI
K M Johnson1, J Z Tao, R P Kennan
1Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA. kevin.johnson@yale.edu
Abstract:
The cytosol of intact human red blood cells was loaded with 28.1 +/- 3.4 mM of dysprosium DTPA-BMA using a hypoosmotic technique. When loaded cells were diluted with saline and control cells to give an average dysprosium concentration of 3.3 +/- 0.5 mM, the transverse relaxation rate constants R(*)(2) and R(2) increased. R(*)(2) increased from 7.5 +/- 0.9 sec(-1) to 356 +/- 50 sec(-1), and R(2) increased from 7.4 +/- 0.7 sec(-1) to 148 +/- 40 sec(-1). After lysing, R(*)(2) was 6.0 +/- 0.6 sec(-1) in the control and 13.4 +/- 1.5 sec(-1) in the mixture; R(2) was 6.4 +/- 1.1 sec(-1) and 9.8 +/- 2.4 sec(-1), respectively. Thus, the relaxivity effects were enhanced by sequestration of the dysprosium within intact red cells, and this effect was lost after lysis. At a circulating whole-blood concentration of 0.81 +/- 0.15 mM in rats, the liver signal intensity dropped 29.9% +/- 3.7% and kidney signal intensity dropped 19.4% +/- 8.7%. Dysprosium-loaded cells might be useful in the study of perfusion and tissue blood volume.
Insights
Dysprosium DTPA-BMA loaded into red blood cells significantly enhances magnetic resonance imaging contrast. This effect, observed in vivo, suggests potential applications for studying blood flow and tissue volume.
Area of Science:
- Biomedical Imaging
- Magnetic Resonance Imaging (MRI)
- Contrast Agents
Background:
- Red blood cells (RBCs) are a potential in vivo delivery vehicle for MRI contrast agents.
- Dysprosium-based contrast agents offer paramagnetic properties for altering water proton relaxation times.
Purpose of the Study:
- To investigate the effect of encapsulating dysprosium DTPA-BMA within intact human red blood cells on MRI relaxivity.
- To evaluate the in vivo efficacy of dysprosium-loaded RBCs as an MRI contrast agent for perfusion and tissue blood volume studies.
Main Methods:
- Human red blood cells were loaded with dysprosium DTPA-BMA via a hypoosmotic technique.
- Transverse relaxation rate constants (R(*)(2) and R(2)) were measured in vitro for loaded and control cells, and after lysis.
- In vivo studies in rats assessed changes in liver and kidney signal intensity after administration of dysprosium-loaded RBCs.
Main Results:
- Encapsulation of dysprosium DTPA-BMA in intact RBCs significantly increased transverse relaxation rates (R(*)(2) and R(2)) compared to lysed cells.
- In vivo, dysprosium-loaded RBCs caused significant signal intensity reductions in rat liver and kidney.
- The enhanced relaxivity effect was dependent on the integrity of the red blood cells.
Conclusions:
- Sequestration of dysprosium DTPA-BMA within intact red blood cells enhances its relaxivity effects.
- Dysprosium-loaded RBCs demonstrate potential as an effective MRI contrast agent for assessing perfusion and tissue blood volume.