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Nanoparticle Contrast-enhanced T1-Mapping Enables Estimation of Placental Fractional Blood Volume in a Pregnant Mouse Model.

ABSTRACT: Non-invasive methods for estimating placental fractional blood volume (FBV) are of great interest for characterization of vascular perfusion in placentae during pregnancy to identify placental insufficiency that may be indicative of local ischemia or fetal growth restriction (FGR). Nanoparticle contrast-enhanced magnetic resonance imaging (CE-MRI) may enable direct placental FBV estimation and may provide a reliable, 3D alternative to assess maternal-side placental perfusion. In this pre-clinical study, we investigated if placental FBV at 14, 16, and 18 days of gestation could be estimated through contrast-enhanced MRI using a long circulating blood-pool liposomal gadolinium contrast agent that does not penetrate the placental barrier. Placental FBV estimates of 0.47?±?0.06 (E14.5), 0.50?±?0.04 (E16.5), and 0.52?±?0.04 (E18.5) were found through fitting pre-contrast and post-contrast T1 values in placental tissue using a variable flip angle method. MRI-derived placental FBV was validated against nanoparticle contrast-enhanced computed tomography (CE-CT) derived placental FBV, where signal is directly proportional to the concentration of iodine contrast agent. The results demonstrate successful estimation of the placental FBV, with values statistically indistinguishable from the CT derived values.

SUBMITTER: Badachhape AA

PROVIDER: S-EPMC6904754 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Nanoparticle Contrast-enhanced T1-Mapping Enables Estimation of Placental Fractional Blood Volume in a Pregnant Mouse Model.

Badachhape Andrew A AA Devkota Laxman L Stupin Igor V IV Sarkar Poonam P Srivastava Mayank M Tanifum Eric A EA Fox Karin A KA Yallampalli Chandrasekhar C Annapragada Ananth V AV Ghaghada Ketan B KB

Scientific reports 20191210 1

Non-invasive methods for estimating placental fractional blood volume (FBV) are of great interest for characterization of vascular perfusion in placentae during pregnancy to identify placental insufficiency that may be indicative of local ischemia or fetal growth restriction (FGR). Nanoparticle contrast-enhanced magnetic resonance imaging (CE-MRI) may enable direct placental FBV estimation and may provide a reliable, 3D alternative to assess maternal-side placental perfusion. In this pre-clinica ...[more]

PMID: 31822711

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Project description:Stress and rest T1-mapping may assess for myocardial ischemia and extracellular volume (ECV). However, the stress T1 response is method-dependent, and underestimation may lead to misdiagnosis. Further, ECV quantification may be affected by time, as well as the number and dosage of gadolinium (Gd) contrast administered. We compared two commonly available T1-mapping approaches in their stress T1 response and ECV measurement stability. Healthy subjects (n = 10, 50% female, 35 ± 8 years) underwent regadenoson stress CMR (1.5 T) on two separate days. Prototype ShMOLLI 5(1)1(1)1 sequence was used to acquire consecutive mid-ventricular T1-maps at rest, stress and post-Gd contrast to track the T1 time evolution. For comparison, standard MOLLI sequences were used: MOLLI 5(3)3 Low (256 matrix) & High (192 matrix) Heart Rate (HR) to acquire rest and stress T1-maps, and MOLLI 4(1)3(1)2 Low & High HR for post-contrast T1-maps. Stress and rest myocardial blood flow (MBF) maps were acquired after IV Gd contrast (0.05 mmol/kg each). Stress T1 reactivity (delta T1) was defined as the relative percentage increase in native T1 between rest and stress. Myocardial T1 values for delta T1 (dT1) and ECV were calculated. Residuals from the identified time dependencies were used to assess intra-method variability. ShMOLLI achieved a greater stress T1 response compared to MOLLI Low and High HR (peak dT1 = 6.4 ± 1.7% vs. 4.8 ± 1.3% vs. 3.8 ± 1.0%, respectively; both p < 0.0001). ShMOLLI dT1 correlated strongly with stress MBF (r = 0.77, p < 0.001), compared to MOLLI Low HR (r = 0.65, p < 0.01) and MOLLI High HR (r = 0.43, p = 0.07). ShMOLLI ECV was more stable to gadolinium dose with less time drift (0.006-0.04% per minute) than MOLLI variants. Overall, ShMOLLI demonstrated less intra-individual variability than MOLLI variants for stress T1 and ECV quantification. Power calculations indicate up to a fourfold (stress T1) and 7.5-fold (ECV) advantage in sample-size reduction using ShMOLLI. Our results indicate that ShMOLLI correlates strongly with increased MBF during regadenoson stress and achieves a significantly higher stress T1 response, greater effect size, and greater ECV measurement stability compared with the MOLLI variants tested.

Project description:PurposeMyocardial T1 relaxation time (T1 time) and extracellular volume fraction (ECV) are altered in patients with diffuse myocardial fibrosis. The purpose of this study was to perform an intra-individual assessment of normal T1 time and ECV for two different contrast agents.MethodsA modified Look-Locker Inversion Recovery (MOLLI) sequence was acquired at 3 T in 24 healthy subjects (8 men; 28 ± 6 years) at mid-ventricular short axis pre-contrast and every 5 min between 5-45 min after injection of a bolus of 0.15 mmol/kg gadopentetate dimeglumine (Gd-DTPA; Magnevist®) (exam 1) and 0.1 mmol/kg gadobenate dimeglumine (Gd-BOPTA; Multihance®) (exam 2) during two separate scanning sessions. T1 times were measured in myocardium and blood on generated T1 maps. ECVs were calculated as ?R1 myocardium/?R1 blood*1-hematocrit.ResultsMean pre-contrast T1 relaxation times for myocardium and blood were similar for both the first and second CMR exam (p > 0.5). Overall mean post-contrast myocardial T1 time was 15 ± 2 ms (2.5 ± 0.7%) shorter for Gd-DTPA at 0.15 mmol/kg compared to Gd-BOPTA at 0.1 mmol/kg (p < 0.01) while there was no significant difference for T1 time of blood pool (p > 0.05). Between 5 and 45 minutes after contrast injection, mean ECV values increased linearly with time for both contrast agents from 0.27 ± 0.03 to 0.30 ± 0.03 (p < 0.0001). Mean ECV values were slightly higher (by 0.01, p < 0.05) for Gd-DTPA compared to Gd-BOPTA. Inter-individual variation of ECV was higher (CV 8.7% [exam 1, Gd-DTPA] and 9.4% [exam 2, Gd-BOPTA], respectively) compared to variation of pre-contrast myocardial T1 relaxation time (CV 4.5% [exam 1] and 3.0% [exam 2], respectively). ECV with Gd-DTPA was highly correlated to ECV by Gd-BOPTA (r = 0.803; p < 0.0001).ConclusionIn comparison to pre-contrast myocardial T1 relaxation time, variation in ECV values of normal subjects is larger. However, absolute differences in ECV between Gd-DTPA and Gd-BOPTA were small and rank correlation was high. There is a small and linear increase in ECV over time, therefore ideally images should be acquired at the same delay after contrast injection.

Project description:ObjectivesWe aimed to evaluate the relationship between mitral annular disjunction (MAD) severity and myocardial interstitial fibrosis at the left ventricular (LV) base in patients with mitral valve prolapse (MVP), and to assess the association between severity of interstitial fibrosis and the occurrence of ventricular arrhythmic events.BackgroundIn MVP, MAD has been associated with myocardial replacement fibrosis and arrhythmia, but the importance of interstitial fibrosis remains unknown.MethodsIn this retrospective study, 30 patients with MVP and MAD (MVP-MAD) underwent cardiovascular magnetic resonance (CMR) with assessment of MAD length, late gadolinium enhancement (LGE), and basal segments myocardial extracellular volume (ECVsyn). The control group included 14 patients with mitral regurgitation (MR) but no MAD (MR-NoMAD) and 10 patients with normal CMR (NoMR-NoMAD). Fifteen MVP-MAD patients underwent 24 h-Holter monitoring.ResultsLGE was observed in 47% of MVP-MAD patients and was absent in all controls. ECVsyn was higher in MVP-MAD (30 ± 3% vs 24 ± 3% MR-NoMAD, p < 0.001 and vs 24 ± 2% NoMR-NoMAD, p < 0.001), even in MVP-MAD patients without LGE (29 ± 3% vs 24 ± 3%, p < 0.001 and vs 24 ± 2%, p < 0.001, respectively). MAD length correlated with ECVsyn (rho = 0.61, p < 0.001), but not with LGE extent. Four patients had history of out-of-hospital cardiac arrest; LGE and ECVsyn were equally performant to identify those high-risk patients, area under the receiver operating characteristic (ROC) curve 0.81 vs 0.83, p = 0.84). Among patients with Holter, 87% had complex ventricular arrhythmia. ECVsyn was above the cut-off value in all while only 53% had LGE.ConclusionIncrease in ECVsyn, a marker of interstitial fibrosis, occurs in MVP-MAD even in the absence of LGE, and was correlated with MAD length and increased risk of out-of-hospital cardiac arrest. ECV should be includedin the CMR examination of MVP patients in an effort to better assess fibrous remodelling as it may provide additional value beyond the assessment of LGE in the arrhythmic risk stratification.

Dataset Information

Nanoparticle Contrast-enhanced T1-Mapping Enables Estimation of Placental Fractional Blood Volume in a Pregnant Mouse Model.

Publications

Nanoparticle Contrast-enhanced T1-Mapping Enables Estimation of Placental Fractional Blood Volume in a Pregnant Mouse Model.

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