Ketan Ghaghada1, Zbigniew Starosolski1, Igor Stupin1, Saakshi Bhayana1, Haijun Gao2, Rohan Bhavane1, Chandresh Patel1, Robia Pautler3, Chandrasekhar Yallampalli2, and Ananth Annapragada1
1Pediatric Radiology, Texas Children's Hospital, Houston, TX, United States, 2Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX, United States, 3Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, United States
Synopsis
Non-invasive imaging of
maternal and placental vasculature in rodent species is of interest to the pre-clinical
study of clinically-relevant placental pathologies.
In this work, we evaluated the utility of high-resolution contrast-enhanced MR angiography
using a placental non-permeable, long circulating liposomal-Gd nanoparticle contrast
agent in a pregnant rat model.Purpose
Methods to safely characterize placenta accreta, placental perfusion, and to molecularly
profile the placenta in vivo, and
longitudinally could greatly enhance
our ability to study and treat placental dysfunction. Currently, a combination
of ultrasound and MRI yields a sensitivity of ~85% for placenta accreta, yet,
the consequences of a circumstantial finding at childbirth are profound,
including massive obstetric hemorrhage, and often, a hysterectomy. Contrast-enhanced MRI (CE-MRI) is an obvious choice, but is currently not recommended due to the
fear of fetal exposure to contrast agent. This study therefore evaluated a
novel liposomal nanoparticle agent that does not cross the placental barrier,
thus preventing fetal exposure [1].
Methods
MR angiography (MRA) was performed
on pregnant Sprague-Dawley rats, using both 1T permanent magnet and 9.4T cryo-cooled
magnet. Conventional contrast agent (DotaremÒ, gadoterate meglumine) and a novel
Gd-containing liposomal nanoparticle contrast agent with 100nm particle size,
and long circulation half-life (~18 hours) were used for contrast-enhanced MRI [2].
A 3D GRE sequence was used for MR-angiography. Dynamic contrast-enhanced MRI
(DCE-MRI) was performed to study the kinetics of contrast agent in the
placenta, and systemic clearance. DCE-MRI was performed using a 2D-GRE sequence with the following parameters: TE=3.4 ms, TR=15ms, flip angle=70°, slice thickness=1.5mm, number of slices = 2, field of view=64 mm, matrix=128x128; scan time = 15 seconds. A total of 60 continuous scans were acquired (total time = 15 minutes) to collect the dynamic data. The contrast agent was administered (0.2 mmol Gd/kg dose) after acquisition of 5 baseline scans. DCE-MRI images were analyzed using the DCE@urLAB software for estimation of perfusion parameters [3].
Results
MRA at both 9.4T and 1T using the
liposomal contrast agent yielded exquisite images of the placental vasculature,
including the penetrating arteries, the central arterial canal, and the
placental labyrinth (Fig 1). DCE-MRI showed that the placental labyrinth fills
first, followed by the decidual region of the placenta, consistent with
previously reported flow dynamics in both rodents and humans. While gadoterate
meglumine showed detectable enhancement in the fetus, the liposomal agent
showed none. Kinetic analysis showed the delayed enhancement of the maternal
decidual region, following immediate enhancement of the placental labyrinth.
Rapid clearance of the gadoterate meglumine from the systemic circulation, and
extremely slow clearance of the liposomal contrast agent were also
demonstrated. Post mortem ICP analysis of the placenta and fetus demonstrated
non-permeation of the liposomal agent through the placental barrier, while
gadoterate meglumine appears to readily cross the barrier.
Conclusion
The study demonstrates the feasibility and
utility of a liposomal gadolinium nanoparticle contrast agent for placental
imaging.
Acknowledgements
The authors would like to acknowledge the Texas Children's Hospital Small Animal Imaging Facility for the use of 9.4T MR scanner.References
1- Annapragada A, Tanifum E, Ghaghada K, Sabapathy,
D. “Super-relaxive Gd nanoparticle.” 21st Annual ISMRM Scientific Meeting in Satl
Lake City, Utah, USA on April 20-26, 2013.
2 - Ghaghada KB, Ravoori M, Gnanasabapathy D,
Bankson J, Kundra V, Annapragada A. “New Dual Mode Gadolinium Nanoparticle
Contrast Agent for Magnetic Resonance Imaging”. PLoS One. 2009; 4(10):e7628.
3 - Ortuño JE, Ledesma-Carbayo MJ, Simões RV, Candiota AP, Arús C, Santos A. "DCE@urLAB: a dynamic contrast-enhanced MRI pharmacokinetic analysis tool for preclinical data". BMC Bioinformatics. 2013; 4(14):316.