Applying Diffusion Basis Spectrum Imaging to Characterize Human Placenta Immuno-Response during Normal Term and Preterm Pregnancies
In this R01 project, we propose to develop a novel, noninvasive human placental immune imaging (PII) technique, which will be able to safely assess human placental inflammation in real time. PII is based on a diffusion MRI technique called diffusion basis spectrum imaging (DBSI), which noninvasively image and quantify brain inflammation in multiple sclerosis in both animal models and humans. Development of PII must take into account the fact that unlike mature brain, the human placenta is a very dynamically changing organ throughout pregnancy, and is quite different from animal placentas. The anatomic and potential pathological complexity and heterogeneity of the placenta create strong background noise interference not present in the brain, making it more challenging to identify and extract the signals specific to placental inflammation.
To address this technical challenge, we are developing PII specifically for human applications by making use of three distinct clinical cohorts.
- Those at low risk of preterm birth
- Those at high risk of preterm birth who respond to preventative hormonal treatment
- Those at high risk of preterm birth who fail to respond to preventative hormonal treatment
To validate PII, we are correlating imaging findings with measurements of immune factors and long non-coding RNAs in maternal blood, and histological characterization of inflammatory cells in placenta samples obtained at delivery.
We expect that this novel imaging modality will help to identify noninvasively placental immune responses characteristic of pregnancies at risk of preterm birth, as well as serve as an objective tool in evaluating success or failure of standard of care preventative treatment.
Ex vivo MRI Immune Imaging of Term and Preterm Human Placentae
As part of validation of the PII technique, we are going to develop a precise sequence using imaging of ex vivo term and preterm placentae.
MR Imaging of Placental Immune Cell Infiltration in Gestational Diabetes Mellitus
We are going to test our new imaging modality, PII, to detect placental immune signature of women with gestational diabetes mellitus (GDM). GDM imposes serious threat to both women with GDM and their babies such as higher risk for pregnancy-related complications, and long-term health problems that could affect their quality of life. We expect that PII could allow for the early diagnosis of relevant complications, and serve as an objective tool for testing the effectiveness of GDM treatment modalities.