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Nanosized T1 MRI Contrast Agent Based on a Polyamidoamine as Multidentate Gd Ligand.

ABSTRACT: A linear polyamidoamine (PAA) named BAC-EDDS, containing metal chelating repeat units composed of two tert-amines and four carboxylic groups, has been prepared by the aza-Michael polyaddition of ethylendiaminodisuccinic (EDDS) with 2,2-bis(acrylamido)acetic acid (BAC). It was characterized by size exclusion chromatography (SEC), FTIR, UV-Vis and NMR spectroscopies. The pKa values of the ionizable groups of the repeat unit were estimated by potentiometric titration, using a purposely synthesized molecular ligand (Agly-EDDS) mimicking the structure of the BAC-EDDS repeat unit. Dynamic light scattering (DLS) and ζ-potential analyses revealed the propensity of BAC-EDDS to form stable nanoaggregates with a diameter of approximately 150 nm at pH 5 and a net negative charge at physiological pH, in line with an isoelectric point <2. BAC-EDDS stably chelated Gd (III) ions with a molar ratio of 0.5:1 Gd (III)/repeat unit. The stability constant of the molecular model Gd-Agly-EDDS (log K = 17.43) was determined as well, by simulating the potentiometric titration through the use of Hyperquad software. In order to comprehend the efficiency of Gd-BAC-EDDS in contrasting magnetic resonance images, the nuclear longitudinal (r1) and transverse (r2) relaxivities as a function of the externally applied static magnetic field were investigated and compared to the ones of commercial contrast agents. Furthermore, a model derived from the Solomon-Bloembergen-Morgan theory for the field dependence of the NMR relaxivity curves was applied and allowed us to evaluate the rotational correlation time of the complex (τ = 0.66 ns). This relatively high value is due to the dimensions of Gd-BAC-EDDS, and the associated rotational motion causes a peak in the longitudinal relaxivity at ca. 75 MHz, which is close to the frequencies used in clinics. The good performances of Gd-BAC-EDDS as a contrast agent were also confirmed through in vitro magnetic resonance imaging experiments with a 0.2 T magnetic field.

SUBMITTER: Arosio P

PROVIDER: S-EPMC8746954 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Nanosized T1 MRI Contrast Agent Based on a Polyamidoamine as Multidentate Gd Ligand.

Arosio Paolo P Cicolari Davide D Manfredi Amedea A Orsini Francesco F Lascialfari Alessandro A Ranucci Elisabetta E Ferruti Paolo P Maggioni Daniela D

Molecules (Basel, Switzerland) 20211228 1

A linear polyamidoamine (PAA) named BAC-EDDS, containing metal chelating repeat units composed of two tert-amines and four carboxylic groups, has been prepared by the aza-Michael polyaddition of ethylendiaminodisuccinic (EDDS) with 2,2-bis(acrylamido)acetic acid (BAC). It was characterized by size exclusion chromatography (SEC), FTIR, UV-Vis and NMR spectroscopies. The pKa values of the ionizable groups of the repeat unit were estimated by potentiometric titration, using ...[more]

PMID: 35011405

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Project description:BackgroundMyocardial T1-rho (T1ρ) mapping is a promising method for identifying and quantifying myocardial injuries without contrast agents, but its clinical use is hindered by the lack of dedicated analysis tools.PurposeTo explore the feasibility of clinically integrated artificial intelligence-driven analysis for efficient and automated myocardial T1ρ mapping.Study typeRetrospective.PopulationFive hundred seventy-three patients divided into a training (N = 500) and a test set (N = 73) including ischemic and nonischemic cases.Field strength/sequenceSingle-shot bSSFP T1ρ mapping sequence at 1.5 T.AssessmentThe automated process included: left ventricular (LV) wall segmentation, right ventricular insertion point detection and creation of a 16-segment model for segmental T1ρ value analysis. Two radiologists (20 and 7 years of MRI experience) provided ground truth annotations. Interobserver variability and segmentation quality were assessed using the Dice coefficient with manual segmentation as reference standard. Global and segmental T1ρ values were compared. Processing times were measured.Statistical testsIntraclass correlation coefficients (ICCs) and Bland-Altman analysis (bias ±2SD); Paired Student's t-tests and one-way ANOVA. A P value <0.05 was considered significant.ResultsThe automated approach significantly reduced processing time (3 seconds vs. 1 minute 51 seconds ± 22 seconds). In the test set, automated LV wall segmentation closely matched manual results (Dice 81.9% ± 9.0) and closely aligned with interobserver segmentation (Dice 82.2% ± 6.5). Excellent ICCs were achieved on a patient basis (0.94 [95% CI: 0.91 to 0.96]) with bias of -0.93 cm2 ± 6.60. There was no significant difference in global T1ρ values between manual (54.9 msec ± 4.6; 95% CI: 53.8 to 56.0 msec, range: 46.6-70.9 msec) and automated processing (55.4 msec ± 5.1; 95% CI: 54.2 to 56.6 msec; range: 46.4-75.1 msec; P = 0.099). The pipeline demonstrated a high level of agreement with manual-derived T1ρ values at the patient level (ICC = 0.85; bias +0.52 msec ± 5.18). No significant differences in myocardial T1ρ values were found between methods across the 16 segments (P = 0.75).Data conclusionAutomated myocardial T1ρ mapping shows promise for the rapid and noninvasive assessment of heart disease.Evidence level3 TECHNICAL EFFICACY: Stage 1.

Dataset Information

Nanosized T1 MRI Contrast Agent Based on a Polyamidoamine as Multidentate Gd Ligand.

Publications

Nanosized <i>T</i><sub>1</sub> MRI Contrast Agent Based on a Polyamidoamine as Multidentate Gd Ligand.

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