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Chemical shift MR imaging methods for the quantification of transcatheter lipiodol delivery to the liver: preclinical feasibility studies in a rodent model.

ABSTRACT: To demonstrate the feasibility of using chemical shift magnetic resonance (MR) imaging fat-water separation methods for quantitative estimation of transcatheter lipiodol delivery to liver tissues.Studies were performed in accordance with institutional Animal Care and Use Committee guidelines. Proton nuclear MR spectroscopy was first performed to identify lipiodol spectral peaks and relative amplitudes. Next, phantoms were constructed with increasing lipiodol-water volume fractions. A multiecho chemical shift-based fat-water separation method was used to quantify lipiodol concentration within each phantom. Six rats served as controls; 18 rats underwent catheterization with digital subtraction angiography guidance for intraportal infusion of a 15%, 30%, or 50% by volume lipiodol-saline mixture. MR imaging measurements were used to quantify lipiodol delivery to each rat liver. Lipiodol concentration maps were reconstructed by using both single-peak and multipeak chemical shift models. Intraclass and Spearman correlation coefficients were calculated for statistical comparison of MR imaging-based lipiodol concentration and volume measurements to reference standards (known lipiodol phantom compositions and the infused lipiodol dose during rat studies).Both single-peak and multipeak measurements were well correlated to phantom lipiodol concentrations (r(2) > 0.99). Lipiodol volume measurements were progressively and significantly higher when comparing between animals receiving different doses (P < .05 for each comparison). MR imaging-based lipiodol volume measurements strongly correlated with infused dose (intraclass correlation coefficients > 0.93, P < .001) with both single- and multipeak approaches.Chemical shift MR imaging fat-water separation methods can be used for quantitative measurements of lipiodol delivery to liver tissues.

SUBMITTER: Yin X

PROVIDER: S-EPMC3359518 | biostudies-other | 2012 Jun

REPOSITORIES: biostudies-other

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Project description:Fat fraction quantification and assessment of its distribution in the hepatic tissue become more important with the growing epidemic of obesity, and the increasing prevalence of diabetes mellitus type 2 and non-alcoholic fatty liver disease. At 3Tesla, the multi-echo, chemical-shift-encoded magnetic resonance imaging (CSE-MRI)-based acquisition allows the measurement of proton density fat-fraction (PDFF) even in clinical protocols. Further improvements in SNR can be achieved by the use of phased array coils and increased static magnetic field. The purpose of the study is to evaluate the feasibility of PDFF imaging using a multi-echo CSE-MRI technique at ultra-high magnetic field (7Tesla). Thirteen volunteers (M/F) with a broad range of age, body mass index, and hepatic PDFF were measured at 3 and 7T by multi-gradient-echo MRI and single-voxel spectroscopy MRS. All measurements were performed in breath-hold (exhalation); the MRI protocols were optimized for a short measurement time, thus minimizing motion-related problems. 7T data were processed off-line using Matlab® (MRI:multi-gradient-echo) and jMRUI (MRS), respectively. For quantitative validation of the PDFF results, a similar protocol was performed at 3T, including on-line data processing provided by the system manufacturer, and correlation analyses between 7 and 3T data were performed off-line. The multi-echo CSE-MRI measurements at 7T with a phased-array coil configuration and an optimal post-processing yielded liver volume coverage ranging from 30 to 90% for high- and low-BMI subjects, respectively. PDFFs ranged between 1 and 20%. We found significant correlations between 7T MRI and -MRS measurements (R2 ≅ 0.97; p < 0.005), and between MRI-PDFF at 7T and 3T fields (R2 ≅ 0.94; p < 0.005) in the evaluated volumes. Based on the measurements and analyses performed, the multi-echo CSE-MRI method using a 32-channel coil at 7T showed its aptitude for MRI-based quantitation of PDFF in the investigated volumes. The results are the first step toward qMRI of the whole liver at 7T with further improvements in hardware.

Project description:PurposeTo explore, at a high field strength of 7T, the performance of various fat spectral models on the quantification of triglyceride composition and proton density fat fraction (PDFF) using chemical-shift encoded MRI (CSE-MRI).MethodsMR data was acquired from CSE-MRI experiments for various fatty materials, including oil and butter samples and in vivo brown and white adipose mouse tissues. Triglyceride composition and PDFF were estimated using various a priori 6- or 9-peak fat spectral models. To serve as references, NMR spectroscopy experiments were conducted to obtain material specific fat spectral models and triglyceride composition estimates for the same fatty materials. Results obtained using the spectroscopy derived material specific models were compared to results obtained using various published fat spectral models.ResultsUsing a 6-peak fat spectral model to quantify triglyceride composition may lead to large biases at high field strengths. When using a 9-peak model, triglyceride composition estimations vary greatly depending on the relative amplitudes of the chosen a priori spectral model, while PDFF estimations show small variations across spectral models. Material specific spectroscopy derived spectral models produce estimations that better correlate with NMR spectroscopy estimations in comparison to those obtained using non-material specific models.ConclusionAt a high field strength of 7T, a material specific 9-peak fat spectral model, opposed to a widely accepted or generic human liver model, is necessary to accurately quantify triglyceride composition when using CSE-MRI estimation methods that assume the spectral model to be known as a priori information. CSE-MRI allows for the quantification of the spatial distribution of triglyceride composition for certain in vivo applications. Additionally, PDFF quantification is shown to be independent of the chosen a priori spectral model, which agrees with previously reported results obtained at lower field strengths (e.g. 3T).

Project description:PurposeTo develop bile acid-stabilized multimodal magnetic resonance (MR) imaging and computed tomography (CT)-visible doxorubicin eluting lipiodol emulsion for transarterial chemoembolization of hepatocellular carcinoma (HCC).Materials and methodsFerumoxytol, a US Food and Drug Administration-approved iron oxide nanoparticle visible under MR imaging was electrostatically complexed with doxorubicin (DOX). An amphiphilic bile acid, sodium cholate (SC), was used to form a stable dispersion of ferumoxytol-DOX complex in lipiodol emulsion. Properties of the fabricated emulsion were characterized in various component ratios. Release kinetics of DOX were evaluated for the chemoembolization applications. Finally, in vivo multimodal MR imaging/CT imaging properties and potential therapeutic effects upon intra-arterial (IA) infusion bile acid-stabilized ferumoxytol-DOX-lipiodol emulsion were evaluated in orthotopic McA-Rh7777 HCC rat models.ResultsDOX complexed with ferumoxytol through electrostatic interaction. Amphiphilic SC bile acid at the interface between the aqueous ferumoxytol-DOX complexes and lipiodol enabled a sustained DOX release (17.2 ± 1.6% at 24 hours) at an optimized component ratio. In McA Rh7777 rat HCC model, IA-infused emulsion showed a significant contrast around tumor in both T2-weighted MR imaging and CT images (P = .044). Hematoxylin and eosin and Prussian blue staining confirmed the local deposition of IA-infused SC bile acid-stabilized emulsion in the tumor. The deposited emulsion induced significant increases in TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) stain-positive cancer cell apoptosis compared to those in a group treated with the nonstabilized emulsion.ConclusionsSC bile acid-stabilized ferumoxytol-DOX-lipiodol emulsion demonstrated sustained drug release and multimodal MR imaging/CT imaging capabilities. The new lipiodol-based formulation may enhance the therapeutic efficacy of chemoembolization in HCC.

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Chemical shift MR imaging methods for the quantification of transcatheter lipiodol delivery to the liver: preclinical feasibility studies in a rodent model.

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