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.

Public Health Relevance

In this project, we use a novel liposomal MRI contrast agent based technology to study Morbidly Adherent Placenta (MAP)adevastatingconditioninpregnancy,whosehallmarkisextensiveinvasionoftheplacentaintotheuterinewall.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD094347-03
Application #
9844860
Study Section
Special Emphasis Panel (ZHD1)
Program Officer
Weinberg, David H
Project Start
2018-02-16
Project End
2023-01-31
Budget Start
2020-02-01
Budget End
2021-01-31
Support Year
3
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Baylor College of Medicine
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030