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Ductal carcinoma in situ: X-ray fluorescence microscopy and dynamic contrast-enhanced MR imaging reveals gadolinium uptake within neoplastic mammary ducts in a murine model.

ABSTRACT: To combine dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging with x-ray fluorescence microscopy (XFM) of mammary gland tissue samples from mice to identify the spatial distribution of gadolinium after intravenous injection.C3(1) Sv-40 large T antigen transgenic mice (n = 23) were studied with institutional animal care and use committee approval. Twelve mice underwent DCE MR imaging after injection of gadodiamide, and gadolinium concentration-time curves were fit to a two-compartment pharmacokinetic model with the following parameters: transfer constant (K(trans)) and volume of extravascular extracellular space per unit volume of tissue (v(e)). Eleven mice received gadodiamide before XFM. These mice were sacrificed 2 minutes after injection, and frozen slices containing ducts distended with murine ductal carcinoma in situ (DCIS) were prepared for XFM. One mouse received saline and served as the control animal. Elemental gadolinium concentrations were measured in and around the ducts with DCIS. Hematoxylin-eosin-stained slices of mammary tissues were obtained after DCE MR imaging and XFM.Ducts containing DCIS were unambiguously identified on MR images. DCE MR imaging revealed gadolinium uptake along the length of ducts with DCIS, with an average K(trans) of 0.21 min(-1) +/- 0.14 (standard deviation) and an average v(e) of 0.40 +/- 0.16. XFM revealed gadolinium uptake inside ducts with DCIS, with an average concentration of 0.475 mmol/L +/- 0.380; the corresponding value for DCE MR imaging was 0.30 mmol/L +/- 0.13.These results provide insight into the physiologic basis of contrast enhancement of DCIS lesions on DCE MR images: Gadolinium penetrates and collects inside neoplastic ducts.

SUBMITTER: Jansen SA

PROVIDER: S-EPMC2770112 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

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Ductal carcinoma in situ: X-ray fluorescence microscopy and dynamic contrast-enhanced MR imaging reveals gadolinium uptake within neoplastic mammary ducts in a murine model.

Jansen Sanaz A SA Paunesku Tatjana T Fan Xiaobing X Woloschak Gayle E GE Vogt Stefan S Conzen Suzanne D SD Krausz Thomas T Newstead Gillian M GM Karczmar Gregory S GS

Radiology 20091101 2

<h4>Purpose</h4>To combine dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging with x-ray fluorescence microscopy (XFM) of mammary gland tissue samples from mice to identify the spatial distribution of gadolinium after intravenous injection.<h4>Materials and methods</h4>C3(1) Sv-40 large T antigen transgenic mice (n = 23) were studied with institutional animal care and use committee approval. Twelve mice underwent DCE MR imaging after injection of gadodiamide, and gadolinium ...[more]

PMID: 19864527

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Project description:BackgroundProton resonance frequency shift (PRFS) magnetic resonance (MR) thermometry exploits the local magnetic field changes induced by the temperature dependence of the electron screening constant of water protons. Any other local magnetic field changes will therefore translate into incorrect temperature readings and need to be considered accordingly. Here, we investigated the susceptibility changes induced by the inflow and presence of a paramagnetic MR contrast agent and their implications on PRFS thermometry.MethodsPhantom measurements were performed to demonstrate the effect of sudden gadopentetate dimeglumine (Gd-DTPA) inflow on the phase shift measured using a PRFS thermometry sequence on a clinical 3 T magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) system. By proton nuclear magnetic resonance spectroscopy, the temperature dependence of the Gd-DTPA susceptibility was measured, as well as the effect of liposomal encapsulation and release on the bulk magnetic susceptibility of Gd-DTPA. In vivo studies were carried out to measure the temperature error induced in a rat hind leg muscle upon intravenous Gd-DTPA injection.ResultsThe phantom study showed a significant phase shift inside the phantom of 0.6 ± 0.2 radians (mean ± standard deviation) upon Gd-DTPA injection (1.0 mM, clinically relevant amount). A Gd-DTPA-induced magnetic susceptibility shift of ΔχGd-DTPA = 0.109 ppm/mM was measured in a cylinder parallel to the main magnetic field at 37°C. The temperature dependence of the susceptibility shift showed dΔχGd-DTPA/dT = -0.00038 ± 0.00008 ppm/mM/°C. No additional susceptibility effect was measured upon Gd release from paramagnetic liposomes. In vivo, intravenous Gd-DTPA injection resulted in a perceived temperature change of 2.0°C ± 0.1°C at the center of the hind leg muscle.ConclusionsThe use of a paramagnetic MR contrast agent prior to MR-HIFU treatment may influence the accuracy of the PRFS MR thermometry. Depending on the treatment workflow, Gd-induced temperature errors ranging between -4°C and +3°C can be expected. Longer waiting time between contrast agent injection and treatment, as well as shortening the ablation duration by increasing the sonication power, will minimize the Gd influence. Compensation for the phase changes induced by the changing Gd presence is difficult as the magnetic field changes are arising nonlocally in the surroundings of the susceptibility change.

Project description:BackgroundWe compared T1- and T2-weighted signal intensities of liver-specific (gadoxetate, gadobenate) and non-specific (gadoterate) gadolinium contrast agents (CAs) in a bile phantom.MethodsIn a phantom study, gadoxetate, gadobenate, and gadoterate were diluted in saline, blood, and bile at different concentrations (0, 0.25, 0.5. 1, 2.5, 5, 10, and 25 mM) and imaged in a 3-T magnetic resonance imaging (MRI) system using T1- and T2-weighted sequences. The maximum signal intensities of CAs were compared for each sequence separately and across all T1-weighted sequences using one-way ANOVA.ResultsUsing T1-weighted sequences, CA concentration-dependent signal intensity increase was followed by decrease due to T2* effects. Comparing CAs for each sequence in bile yielded higher maximum signal intensities with gadobenate than gadoxetate and gadoterate using T1-weighted spin-echo (p < 0.010), multiecho gradient- and spin-echo (p < 0.001), and T1-weighted high-resolution isotropic volume excitation (eTHRIVE) sequences (p < 0.010). Comparing across all T1-weighted sequences in the bile phantom, gadobenate imaged using T1-weighted turbo field-echo (TFE) sequence showed the highest signal intensity, significantly higher than that using other CAs agents or sequences (p < 0.004) except for gadobenate and gadoxetate evaluated with three-dimensional multiecho fast field-echo (3D-mFFE) and gadoxetate with T1-weighted TFE sequence (p > 0.141). Signal reduction with CA concentration-dependent decrease was observed on T2-weighted images.ConclusionIn this bile phantom study of gadolinium-based CA, gadobenate and gadoxetate showed high signal intensity with T1-weighted TFE and 3D-mFFE sequences, which supports their potential utility for contrast-enhanced hepatobiliary MRI.Key points• Contrast-enhanced magnetic resonance (MR) cholangiography depends on contrast agent type, kinetics, and concentration in bile, • We compared signal intensities of three contrast agents in a bile phantom study. • Gadobenate, gadoxetate, and gadoterate demonstrated different signal intensities at identical concentrations. • Gadoxetate and gadobenate showed high signal intensities on T1-weighted MR sequences.

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Dataset Information

Ductal carcinoma in situ: X-ray fluorescence microscopy and dynamic contrast-enhanced MR imaging reveals gadolinium uptake within neoplastic mammary ducts in a murine model.

Publications

Ductal carcinoma in situ: X-ray fluorescence microscopy and dynamic contrast-enhanced MR imaging reveals gadolinium uptake within neoplastic mammary ducts in a murine model.

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