Paramagnetic Long-circulating Liposome And Gd-DTPA For CE-MRA Comparative Study

PurposeAt present,the clinical main application is as Gd-DTPA the same as the low molecular weight gadolinium chelates for CE-MRA examination. The half-life of these low-molecular weight gadolinium chelates is short in vivo, and the requirement for the scanning phase is strict, the display of the small blood vessels is poor (such as the spinal cord blood vessels), and there is a difference with the images of digital subtraction angiography (DSA). We synthesis the connectting Gd-DMPE-DTPA of long-circulating liposomes, and through the CE-MRA of animal models to explore its long-circulating properties in vivo and the possibility of clearly imaging for the blood vessels (especially the small blood vessels).Materials and methodsWe use DMPE-DTPA, OPPC, M-PEG-2000-PE, and GdCL3.6H2O etc.to synthesis paramagnetic long-circulating liposome by Thin Film Hydration method. the inner and outer surfaces of the lipid bilayer connecte the Gd-DMPE-DTPA. We analyze and measure the particle's shape and size by transmission electron microscopy.We choose six healthy rabbits with an average body weight (1.5±0.25) kg, randomly divide into two groups,which were given liposome or Gd-DTPA after general anesthesia. We use the knee coil to do the CE-MRA scan to the lower abdomen, pelvis and both lower limbs at the 3.0 T magnetic resonance scanner (GE Signa 3.0T HDX superconducting type). Firstly scan a mask before Administration,then,respectively do a scan at the injection,5 minutes,15minutes,25minutes,30minutes,60minutes and 180 minutes. At first, we conduct a preliminary evaluation of the quality of the all original coronal images on the GE ADW 4.4 workstation, and the display of the abdominal aorta,inferior vena cava,bilateral iliac vessels and their branches; then, apply subtraction technique to remove identical organizational context; Finally we use MIP,MPR and VR to reconstruct the three-dimensional image, and observe and analyze the display of target vessel.We measure the signal intensity at the five region of interest of coronal source images. the average date is the signal intensity value of target vessels. In order to ensure all measured parts of all phases similar,we fixe vascular openings as reference. We place region of interest at psoas major muscle's signal uniformity near blood vessels, the standard deviation of the measured values as the image background noise at the phase-encoding direction. Two kinds of contrast agent were calculated the SNR (signal-to-noise ratio,SNR) and contrast-noise ratio (contrast-to-noise ratio,CNR)at different time points.ResultsParamagnetic long-circulating liposome solution is pale yellow, clear and translucent. The mean diametre of liposme is 143nm, the liposme is round or roundlike, the size is uniform, and don't aggregate.comparing the images with that of mask, paramagnetic long-circulating liposome and Gd-DTPA can markedly enhance the blood vessels, intravascular signal intensity was significantly higher. the SI blood vessels (t) curve,SNR (t) curve and CNR (t) curve show that the peak time of intravascular signal of paramagnetic long-circulating liposome and Gd-DTPA is similar, but the former's duration is longer than the latter, the peak signal intensity is not significant difference (P>0.05), but the signal intensity of paramagnetic liposomes is significantly higher than Gd-DTPA after 5 minutes (P<0.05). The SI, SNR and CNR of paramagnetic liposome's blood vessels images change slowly over time; The SI, SNR and CNR of Gd-DTPA's blood vessels images change rapidly over time. Paramagnetic long-circulating liposomes can better show the abdominal aorta,inferior vena cava,bilateral iliac vessels and their main branches within 60 minutes, and the small blood vessels can be displayed on the target area very well in 5 minutes; Gd-DTPA can only show the abdominal aorta,inferior vena cava and their main branches in 10 minutes, and worse show the small blood vessels on the target area than paramagnetic long-circulating liposomes.Conclusionthe particle size of the Gd-DMPE-DTPA paramagnetic long-circulating liposome we prepared is uniform. It can image the blood vessels,especially the small blood vessels, for a long time and can be confirmed by in vivo MR imaging.