We propose a novel platform technology based on liposomal MRI imaging agents that provide methodology for safe, facile vascular and molecular imaging of the placenta. We focus in this application on Morbidly Adherent Placenta (MAP: classified as placenta accreta, increta or percreta), and will demonstrate the power of this technology for the study of this condition, noting that the technology once developed will be applicable to numerous other placental conditions. Diagnosis of MAP remains challenging, even with ultrasound followed by MRI in indeterminate cases: only about half of the cases of MAP are suspected prior to childbirth15. MAP results in massive blood loss (25% of cases), hysterectomy(70%ofcases)andICUadmission(30%ofcases),atratesfarhigherthanthenon-?MAPpopulation. The detection of a ?retroplacental clear space? is a marker of normal placentation. Further, the level of adrenomedullinanditsreceptor(theCRCLR/RAMP2complex)isthoughttobeanearlymarkerofMAP.
The specificaims ofthisprojectaretherefore 1. QuantifyplacentalmargindelineationwiththeliposomalGdcontrastagent,inrodentmodels. a. Test the visualization of the ?retroplacental clear space?, a poorly vascularized layer between the placentaandthemyometrialwall,asameasureofmargindelineation,asafunctionofgestationalage. b. Comparedetectionoftheretroplacentalclearspaceandplacentalmarginswithnon-?contrastMRIand conventionalGdchelates,throughthecourseofgestation. 2. TestwhetherthespatialexpressionoftheAdrenomedullinreceptor(CRCLR/RAMP2)intheplacentaanduterine wallcorrelatewithplacentalinvasion,acrossarangeofgestationalages. a. Visualize and quantify CRCLR/RAMP2 with MRI using an adrenomedullin targeted Gd liposome, and validateusingimmunohistochemistry b. CorrelateCRCLR/RAMP2levelswithimagingbasedmargindelineationandhistologicallydetermined placentalinvasionthroughoutgestation.
In this project, we use a novel liposomal MRI contrast agent based technology to study Morbidly Adherent Placenta (MAP)adevastatingconditioninpregnancy,whosehallmarkisextensiveinvasionoftheplacentaintotheuterinewall.
