Summary

Contrast-enhanced MRI is effective for noninvasive visualization of the real-time pharmacokinetics and biodistribution of paramagnetically labeled polymer drug conjugates after intravenous administration. The technique provides three-dimensional anatomic images of soft tissues with high spatial resolution. The circulation and accumulation of the paramagnetic polymeric conjugates in organs or tissues result in bright signal for T1-weighted images. Dynamic contrast-enhanced MRI clearly reveals circulation of the conjugates in the blood, interaction with the major organs, including the liver, heart, kidneys, etc., and accumulation and clearance in the target tissues. It also provides information on the dynamic changes of the distribution patterns of polymer conjugates in solid tumor tissues, which cannot be obtained with conventional pharmacokinetic methods. Such a detailed map of the delivery system deposition within the tissue and its correlation with the local pathologic features may help to optimize the structure of the polymeric drug conjugate to achieve high drug delivery efficiency. One limitation of contrast-enhanced MRI is the accurate quantification of the concentrations of the conjugates in the tissues and organs. Several technical factors control the accurate measurement of concentrations of contrast agents with conventional contrast-enhanced MRI. For quantitative study of in vivo drug delivery with paramagnetic conjugates, MR T1 mapping can be used because T1 relaxation rate (1/Tj) is linearly proportional to the concentration of MRI contrast agents. Data acquisition and algorithms to process the data for T1 mapping are more complicated than for conventional contrast-enhanced MRI.

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