Pre-clinical evaluation of a nanoparticle-based blood-pool contrast agent for MR imaging of the placenta

• Published in: Placenta (Eastbourne) 2017-09, Vol.57, p.60-70
• Main Authors: Ghaghada, Ketan B, Starosolski, Zbigniew A, Bhayana, Saakshi, Stupin, Igor, Patel, Chandreshkumar V, Bhavane, Rohan C, Gao, Haijun, Bednov, Andrey, Yallampalli, Chandrasekhar, Belfort, Michael, George, Verghese, Annapragada, Ananth V
• Format: Article
• Language: English
• Subjects: Animals; Blood pool contrast agent; Contrast Media; Female; Gadolinium; Humans; In Vitro Techniques; Internal Medicine; Liposomal-Gd; Liposomes; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Obstetrics and Gynecology; Placenta; Placenta - diagnostic imaging; Pregnancy; Pregnant rat model; Rats; Rats, Sprague-Dawley; Retroplacental space
• ISSN: 0143-4004; 1532-3102
• DOI: 10.1016/j.placenta.2017.06.008

Abstract Introduction Non-invasive 3D imaging that enables clear visualization of placental margins is of interest in the accurate diagnosis of placental pathologies. This study investigated if contrast-enhanced MRI performed using a liposomal gadolinium blood-pool contrast agent (liposomal-Gd) enables clear visualization of the placental margins and the placental-myometrial interface (retroplacental space). Non-contrast MRI and contrast-enhanced MRI using a clinically approved conventional contrast agent were used as comparators. Materials and methods Studies were performed in pregnant rats under an approved protocol. MRI was performed at 1T using a permanent magnet small animal scanner. Pre-contrast and post-liposomal-Gd contrast images were acquired using T1-weighted and T2-weighted sequences. Dynamic Contrast enhanced MRI (DCE-MRI) was performed using gadoterate meglumine (Gd-DOTA, Dotarem® ). Visualization of the retroplacental clear space, a marker of normal placentation, was judged by a trained radiologist. Signal-to-noise (SNR) and contrast-to-noise (CNR) ratios were calculated for both single and averaged acquisitions. Images were reviewed by a radiologist and scored for the visualization of placental features. Contrast-enhanced CT (CE-CT) imaging using a liposomal CT agent was performed for confirmation of the MR findings. Transplacental transport of liposomal-Gd was evaluated by post-mortem elemental analysis of tissues. Ex-vivo studies in perfused human placentae from normal, GDM, and IUGR pregnancies evaluated the transport of liposomal agent across the human placental barrier. Results Post-contrast T1w images acquired with liposomal-Gd demonstrated significantly higher SNR (p = 0.0002) in the placenta compared to pre-contrast images (28.0 ± 4.7 vs. 6.9 ± 1.8). No significant differences (p = 0.39) were noted between SNR in pre-contrast and post-contrast liposomal-Gd images of the amniotic fluid, indicating absence of transplacental passage of the agent. The placental margins were significantly (p