Magnetic Resonance Colonography With Intestine-absorbable Nanoparticle Contrast Agents In Evaluation Of Colorectal Inflammation

Purpose:To develop a nanoparticle-based magnetic resonance colon imaging technique,which enabled us to evaluate ulcerative colitis via transrectal administration of intestine-absorbable nanoparticle contrast agents,and to further confirm the intestinal absorption of contrast agent by fluorescence microscope.Methods:Solid lipid nanoparticles(SLNs)were synthesized with loading of gadolinium(Gd)diethylenetriaminepenta acetic acid(Gd-DTPA)and otcadecylamine fluorescein isothiocyanate(FITC)to construct Gd-FITC-SLNs for T1 contrast agent and histologic confirmation of MR findings.For in vivo validation,there is a total of 25 mice with 2grades UC(acute,n = 20;and chronic,n = 5)and 5 mice without UC.Twenty mice of dextran sodium sulphate(DSS)-induced acute UC were divided into 4 groups includingenema with Gd-FITC-SLNs,n = 5;intravenous injection with Gd-FITC-SLNs,n = 5;enema with Gd-DTPA;and intravenous injection with Gd-DTPA,n=5.Five mice with chronic UC and 5 mice without UC were treated with Gd-FITC-SLNs enema.All mice were examined using a 3.0-T with a small animal MR coil.T1-axial and T2-axial weighted MR images were then performed before and 20,40,60,80,100 and 120 min after enema(1ml/per)or of intravenous-injection(0.1 mmol Gd/kg body weight)contrast agent(Gd-FITC-SLNs or Gd-DTPA).The signal to noise ratios(SNRs)of the rectal wall were measured.MRI findings were correlated with subsequent histological confirmation.Results:After 20 minutes of retention enema with nano contrast agent Gd-FITC-SLNs,dynamic MR imaging showed that the colorectal wall was enhanced due to the absorption of nano contrast agent.The degree of enhancement was acute UC > normal intestinal wall > chronic UC,and the acute UC was continuously enhanced for 120 minute.The normal intestinal wall was rapidly metabolized and the degree of enhancement decreased,while the colorectal wall of the chronic UC was only slightly enhanced.There was no significant difference(8.09±1.21 vs.8.09±1.71,P > 0.05)in the signal-to-noise ratio of the intestinal wall between intravenous Gd-DTPA and transrectal Gd-FITC-SLNs at 20 minutes.During MRI,transrectal infusion of Gd-FITC-SLNs at20,40,60 and 80 minutes showed more significant enhancement of colitic walls compared with the transrectal infusion of Gd-DTPA,especially after 20 and 40 minutes.The SNR of the rectal wall after intravenous infusion of Gd-FITC-SLNs showed higher at all time points than those with Gd-DTPA(p<0.01).Confocal fluorescence microscopy showed that Gd-FITC-SLNs as highly-concentrated green fluorescent spots accumulate the colonic walls of colitic mice for enema group and intravenous injectiongroup with Gd-FITC-SLNs.Conclusion:Enema with Gd-SLNs is helpful for the diagnosis and differential diagnosis of acute and chronic ulcerative colitis,and it can achieve the same or better effect as intravenous injection of Gd-DTPA.Solid lipid nanoparticle-based MR colonography enhances inflammatory colorectum based on absorption of nanoparticle contrast agents by colorectal wall,which may open new avenues for diagnosis and efficient management of ulcerative colitis.