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Updated: Jul 16, 2026
Molecular Imaging to Target Transplanted Muscle Progenitor Cells
Published on: March 27, 2013
Magnetic resonance imaging-monitored plasmid DNA delivery in primate limb muscle
Karl K Vigen1, Julia O Hegge, Guofeng Zhang
1Department of Radiology, University of Wisconsin-Madison, Madison, WI 53792, USA. kkvigen@wisc.edu
Abstract:
The purpose of this work is to investigate the use of magnetic resonance imaging (MRI) to monitor the effects of high-pressure naked plasmid DNA (pDNA) intravascular injections in primate limbs, studying both the distribution of the injected solution in the muscle space, as well as the effects on the vascular system. The distal portion of the four limbs of each of six rhesus monkeys were hydrodynamically injected with naked pDNA, which expressed the luciferase reporter gene. Three-dimensional (3D) T1-weighted gradient echo and 2D multislice T2-weighted fast spin echo (FSE) series were acquired before and immediately after the injection to confirm the volume of solution injected into the limb, and to study the distribution of the injected solution in the individual muscle groups. Time-resolved contrast-enhanced 3D magnetic resonance angiography (MRA) was performed several days before, immediately after, and in a follow-up examination after the pDNA injection to study the effects of the procedure on the primate peripheral vascular system. T1-weighted gradient echo imaging confirmed the delivery of the majority of the solution after successful pDNA injections. T2-weighted FSE imaging demonstrated the distribution of the saline solution in individual muscles in the target limbs, with enhancement showing a weak but significant correlation with the level of gene expression. Time-resolved contrast-enhanced MRA demonstrated effects of the injection procedure on the arterial and venous vascular systems, and the intramuscular compartments; and these effects largely returned to normal on short-term follow-up.
Insights
Magnetic resonance imaging (MRI) effectively monitored naked plasmid DNA (pDNA) injections in primate limbs, assessing solution distribution and vascular effects. The study confirmed successful delivery and showed temporary vascular changes that resolved with follow-up.
Area of Science:
- Biomedical Imaging
- Gene Therapy Delivery
- Primate Models
Background:
- Naked plasmid DNA (pDNA) delivery via hydrodynamic injection is a gene therapy technique.
- Monitoring solution distribution and vascular impact is crucial for optimizing this method.
- Non-invasive imaging modalities are needed to assess these effects in vivo.
Purpose of the Study:
- To evaluate magnetic resonance imaging (MRI) for monitoring high-pressure naked plasmid DNA (pDNA) intravascular injections in primate limbs.
- To assess the distribution of injected solution within muscle tissue.
- To investigate the effects of the injection procedure on the peripheral vascular system.
Main Methods:
- Six rhesus monkeys received hydrodynamic injections of naked pDNA in their distal limbs.
- 3D T1-weighted and 2D T2-weighted MRI sequences were used for pre- and post-injection imaging.
- Time-resolved contrast-enhanced 3D magnetic resonance angiography (MRA) was performed at multiple time points.
Main Results:
- T1-weighted MRI confirmed successful delivery of the majority of the injected solution.
- T2-weighted MRI visualized solution distribution in individual muscles, correlating weakly with gene expression.
- MRA revealed temporary effects on arterial and venous systems, which largely normalized on follow-up.
Conclusions:
- MRI is a valuable tool for assessing pDNA distribution and vascular effects after hydrodynamic injection in primates.
- The injection procedure causes transient vascular alterations that typically resolve.
- Further optimization of gene delivery techniques can be guided by imaging findings.
