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

Ghaghada, Ketan B.; Starosolski, Zbigniew; Bhayana, Saakshi; Stupin, Igor; Patel, Chandreshkumar; Bhavane, Rohan; Gao, Haijun; Bednov, Andrey A.; Yallampalli, Chandra; Belfort, Michael A.; George, Vineeth; Annapragada, Ananth

doi:10.1016/j.placenta.2017.06.008

Cited by 37 publications

(32 citation statements)

References 25 publications

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“…The mean particle size of liposomes was determined using a Dynamic Light Scattering (DLS) instrument (Brookhaven Instruments Corp., Holtsville, NY, USA). Total phospholipid content of liposomal formulations was determined by measuring total phosphorus using inductively-coupled plasma atomic emission spectroscopy (ICP-AES) 44 . ICG concentration was determined by dissolving liposomal-ICG in dimethyl sulfoxide (DMSO) (1000x dilution) and measuring fluorescence (ex: 785 nm, em: 810–830 nm) using a Pioneer camera (Basler, Ahrensburg, Germany), with a Sony ICX625 CCD sensor 2456 × 2058 pixels (5 Mpixels), fitted with 810–830 nm bandpass filter.…”

Section: Methodsmentioning

confidence: 99%

“…For brain imaging studies, animals were administered a long circulating blood pool liposomal-Gadolinium (liposomal-Gd, 0.1 mmol Gd/kg) contrast agent for in vivo magnetic resonance angiography (MRA) prepared using methods described previously 44 , 46 . Imaging was performed on a 1 Tesla permanent MRI scanner (M2 system, Aspect Imaging, Shoham, Israel).…”

Section: Methodsmentioning

confidence: 99%

“…Imaging was performed on a 1 Tesla permanent MRI scanner (M2 system, Aspect Imaging, Shoham, Israel). This contrast agent is optimized for maximum contrast-to-noise ratio at this field strength, and enables facile high resolution imaging 44 . A 25 mm volume coil was used for brain imaging.…”

Section: Methodsmentioning

confidence: 99%

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NIR-II fluorescence imaging using indocyanine green nanoparticles

Bhavane

Starosolski

Stupin

et al. 2018

Sci Rep

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Fluorescence imaging in the second near-infrared window (NIR-II) holds promise for real-time deep tissue imaging. In this work, we investigated the NIR-II fluorescence properties of a liposomal formulation of indocyanine green (ICG), a FDA-approved dye that was recently shown to exhibit NIR-II fluorescence. Fluorescence spectra of liposomal-ICG were collected in phosphate-buffered saline (PBS) and plasma. Imaging studies in an Intralipid® phantom were performed to determine penetration depth. In vivo imaging studies were performed to test real-time visualization of vascular structures in the hind limb and intracranial regions. Free ICG, NIR-I imaging, and cross-sectional imaging modalities (MRI and CT) were used as comparators. Fluorescence spectra demonstrated the strong NIR-II fluorescence of liposomal-ICG, similar to free ICG in plasma. In vitro studies demonstrated superior performance of liposomal-ICG over free ICG for NIR-II imaging of deep (≥4 mm) vascular mimicking structures. In vivo, NIR-II fluorescence imaging using liposomal-ICG resulted in significantly (p < 0.05) higher contrast-to-noise ratio compared to free ICG for extended periods of time, allowing visualization of hind limb and intracranial vasculature for up to 4 hours post-injection. In vivo comparisons demonstrated higher vessel conspicuity with liposomal-ICG-enhanced NIR-II imaging compared to NIR-I imaging.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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NIR-II fluorescence imaging using indocyanine green nanoparticles

Bhavane

Starosolski

Stupin

et al. 2018

Sci Rep

Self Cite

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“…Magnetic resonance imaging contrast agents, primarily GBCA, have previously been used to enhance placental visualization and to identify maternal decidual spiral arteries in humans, 42 the rhesus macaque, 15,16,38,43,44 and a variety of small animal models. [45][46][47][48][49][50] However, most GBCAs exchange with the extravascular space. Recently, GBCAs were shown to be at nearly undetectable levels in the fetal and placental tissue in nonhuman primates 51 after intravenous infusion for DCE MRI, but they have previously been observed in the bladder of the fetus.…”

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confidence: 99%

Perfusion of the placenta assessed using arterial spin labeling and ferumoxytol dynamic contrast enhanced magnetic resonance imaging in the rhesus macaque

Ludwig

Fain

Nguyen

et al. 2018

Magnetic Resonance in Med

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Purpose To investigate the correspondence between arterial spin labeling (ASL) flow‐sensitive alternating inversion recovery (FAIR) and ferumoxytol DCE MRI for the assessment of placental intervillous perfusion. Methods Ten pregnant macaques in late second trimester were imaged at 3 T using a 2D ASL FAIR, with and without outer‐volume saturation pulses used to control the bolus width, and a 3D ferumoxytol DCE‐MRI acquisition. The ASL tagged/control pairs were averaged, subtracted, and normalized to create perfusion ratio maps. Contrast arrival time and uptake slope were estimated by fitting the DCE data to a sigmoid function. Macaques (N = 4) received interleukin‐1β to induce inflammation and disrupt perfusion. Results The FAIR tag modification with outer‐volume saturation reduced the median ASL ratio percentage compared with conventional FAIR (0.64% ± 1.42% versus 0.71% ± 2.00%; P < .05). Extended ferumoxytol arrival times (34 ± 25 seconds) were observed across the placenta. No significant DCE signal change was measured in fetal tissue (−0.6% ± 3.0%; P = .52) or amniotic fluid (1.9% ± 8.8%; P = .59). High ASL ratio was significantly correlated with early arrival time and high uptake slope (P < .05), but ASL signal was not above noise in late‐DCE‐enhancing regions. No significant differences were observed in perfusion measurements between the interleukin‐1β and controls (P > .05). Conclusion The ASL‐FAIR and ferumoxytol DCE‐MRI methods are feasible to detect early blood delivery to the macaque placenta. Outer volume saturation reduced the high macrovascular ASL signal. Interleukin‐1β exposure did not alter placental intervillous perfusion. An endogenous‐labeling perfusion technique is limited due to extended transit times for flow within the placenta beyond the immediate vicinity of the maternal spiral arteries.

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“…Direct visual confirmation of an abnormal placental-uterine interface is desirable, especially to clearly delineate normal from adherent or only focally invasive placentas. Recent MR studies of invasive placentation have demonstrated the effectiveness of using gadolinium (Gd) based contrast agents to improve visualization of this interface in both clinical [16] and preclinical [17] applications.…”

Section: Introductionmentioning

confidence: 99%

Pre-clinical magnetic resonance imaging of retroplacental clear space throughout gestation

et al. 2019

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Introduction: Visualization of the retroplacental clear space (RPCS) may provide critical insight into the development of abnormally invasive placenta (AIP). In this pre-clinical study, we characterized the appearance of the RPCS on magnetic resonance imaging (MRI) during the second half of gestation using a liposomal gadolinium contrast agent (liposomal-Gd). Materials and Methods: Studies were performed in fifteen pregnant C57BL/6 mice at 10, 12, 14, 16, and 18 days of gestation. MRI was performed on a 1T permanent magnet scanner. Precontrast and post-contrast images were acquired using T1-weighted gradient-recalled echo (T1w-GRE) and T2-weighted fast spin echo (T2w-FSE) sequences. Animals were euthanized after imaging and feto-placental units harvested for histological examination. Visualization of the RPCS was scored by a maternal-fetal radiologist and quantified by measuring the contrast-to-noise ratio (CNR) on T1w images. Feto-placental features were segmented for analysis of volumetric changes during gestation. Results: Contrast-enhanced T1w images enabled the visualization of structural changes in placental development between days 10 to 18 of gestation. Although the placental margin on the fetal side was clearly visible at all time points, the RPCS was partially visible at day 10 of gestation, and clearly visible by day 12. Hematoxylin and eosin (H&E) staining of the placental tissue corroborated MRI findings of structural and morphological changes in the placenta. Conclusions: Contrast-enhanced MR imaging using liposomal-Gd enabled adequate visualization of the retroplacental clear space starting at day 12 of gestation. The agent also enabled characterization of placental structure and morphological changes through gestation.

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

Cited by 37 publications

References 25 publications

NIR-II fluorescence imaging using indocyanine green nanoparticles

NIR-II fluorescence imaging using indocyanine green nanoparticles

Perfusion of the placenta assessed using arterial spin labeling and ferumoxytol dynamic contrast enhanced magnetic resonance imaging in the rhesus macaque

Pre-clinical magnetic resonance imaging of retroplacental clear space throughout gestation

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