Quantification of carotid plaque composition with a multi-contrast atherosclerosis characterization (MATCH) MRI sequence

Background and purposeCarotid atherosclerotic plaques with a large lipid-rich necrotic core (LRNC), intraplaque hemorrhage (IPH), and a thin or ruptured fibrous cap are associated with increased stroke risk. Multi-sequence MRI can be used to quantify carotid atherosclerotic plaque composition. Yet, its clinical implementation is hampered by long scan times and image misregistration. Multi-contrast atherosclerosis characterization (MATCH) overcomes these limitations. This study aims to compare the quantification of plaque composition with MATCH and multi-sequence MRI.MethodsMATCH and multi-sequence MRI were used to image 54 carotid arteries of 27 symptomatic patients with ≥2 mm carotid plaque on a 3.0 T MRI scanner. The following sequence parameters for MATCH were used: repetition time/echo time (TR/TE), 10.1/4.35 ms; field of view, 160 mm × 160 mm × 2 mm; matrix size, 256 × 256; acquired in-plane resolution, 0.63 mm2× 0.63 mm2; number of slices, 18; and flip angles, 8°, 5°, and 10°. Multi-sequence MRI (black-blood pre- and post-contrast T1-weighted, time of flight, and magnetization prepared rapid acquisition gradient echo; acquired in-plane resolution: 0.63 mm2 × 0.63 mm2) was acquired according to consensus recommendations, and image quality was scored (5-point scale). The interobserver agreement in plaque composition quantification was assessed by the intraclass correlation coefficient (ICC). The sensitivity and specificity of MATCH in identifying plaque composition were calculated using multi-sequence MRI as a reference standard.ResultsA significantly lower image quality of MATCH compared to that of multi-sequence MRI was observed (p < 0.05). The scan time for MATCH was shorter (7 vs. 40 min). Interobserver agreement in quantifying plaque composition on MATCH images was good to excellent (ICC ≥ 0.77) except for the total volume of calcifications and fibrous tissue that showed moderate agreement (ICC ≥ 0.61). The sensitivity and specificity of detecting plaque components on MATCH were ≥89% and ≥91% for IPH, ≥81% and 85% for LRNC, and ≥71% and ≥32% for calcifications, respectively. Overall, good-to-excellent agreement (ICC ≥ 0.76) of quantifying plaque components on MATCH with multi-sequence MRI as the reference standard was observed except for calcifications (ICC = 0.37–0.38) and fibrous tissue (ICC = 0.59–0.70).Discussion and conclusionMATCH images can be used to quantify plaque components such as LRNC and IPH but not for calcifications. Although MATCH images showed a lower mean image quality score, short scan time and inherent co-registration are significant advantages

Evaluation of Iron Oxide Nanoparticle Micelles for Magnetic Particle Imaging (MPI) of Thrombosis

Magnetic particle imaging (MPI) is an emerging medical imaging modality that directly visualizes magnetic particles in a hot-spot like fashion. We recently developed an iron oxide nanoparticle-micelle (ION-Micelle) platform that allows highly sensitive MPI. The goal of this study was to assess the potential of the ION-Micelles for MPI-based detection of thrombi. To this aim, an in vivo carotid artery thrombosis mouse model was employed and ex vivo magnetic particle spectrometer (MPS) measurements of the carotid arteries were performed. In addition, we studied the effect of functionalization of the ION-Micelle nanoplatform with fibrin-binding peptides (FibPeps) with respect to nanoparticle thrombus uptake and hence thrombus detection. In vivo quantitative MR imaging pre- and post-ION-Micelle injection was performed as reference for visualization of ION-micelle uptake. ION-Micelles significantly decreased T2 values in the thrombi with respect to pre-injection T2 values (p < 0.01) and significantly increased ex vivo MPS thrombus signal with respect to the noninjured, contralateral carotid (p < 0.01). Functionalization of the ION-Micelles with the FibPep peptides did not result in an increased MPS thrombus signal with respect to the non-fibrin binding ION-Micelles. The lack of a significant increased thrombus uptake for the FibPep-ION-Micelles indicates that (non-fibrin-specific) entrapment of nanoparticles in the mesh-like thrombi is the key contributor to thrombus nanoparticle uptake. Therefore, (nontargeted) ION-Micelles might be of value for noninvasive MPI-based diagnosis, characterization and treatment monitoring of thrombosis

Spin-lock MR enhances the detection sensitivity of superparamagnetic iron oxide particles

To evaluate spin-lock MR for detecting superparamagnetic iron oxides and compare the detection sensitivity of quantitative T1ρ with T2 imaging. In vitro experiments were performed to investigate the influence of iron oxide particle size and composition on T1ρ . These comprise T1ρ and T2 measurements (B0 = 1.41T) of agar (2%) with concentration ranges of three different iron oxide nanoparticles (IONs) (Sinerem, Resovist, and ION-Micelle) and microparticles of iron oxide (MPIO). T1ρ dispersion was measured for a range of spin-lock amplitudes (γB1 = 6.5-91 kHz). Under relevant in vivo conditions (B0 = 9.4T; γB1 = 100-1500 Hz), T1ρ and T2 mapping of the liver was performed in seven mice pre- and 24 h postinjection of Sinerem. Addition of iron oxide nanoparticles decreased T1ρ as well as the native T1ρ dispersion of agar, leading to increased contrast at high spin-lock amplitudes. Changes of T1ρ were highly linear with iron concentration and much larger than T2 changes. MPIO did not show this effect. In vivo, a decrease of T1ρ was observed with no clear influence on T1ρ dispersion. By suppression of T1ρ dispersion, iron oxide nanoparticles cause enhanced T1ρ contrast compared to T2 . The underlying mechanism appears to be loss of lock. Spin-lock MR is therefore a promising technique for sensitive detection of iron oxide contrast agent

Small animal cardiovascular MR imaging and spectroscopy

The use of MR imaging and spectroscopy for studying cardiovascular disease processes in small animals has increased tremendously over the past decade. This is the result of the remarkable advances in MR technologies and the increased availability of genetically modified mice. MR techniques provide a window on the entire timeline of cardiovascular disease development, ranging from subtle early changes in myocardial metabolism that often mark disease onset to severe myocardial dysfunction associated with end-stage heart failure. MR imaging and spectroscopy techniques play an important role in basic cardiovascular research and in cardiovascular disease diagnosis and therapy follow-up. This is due to the broad range of functional, structural and metabolic parameters that can be quantified by MR under in vivo conditions non-invasively. This review describes the spectrum of MR techniques that are employed in small animal cardiovascular disease research and how the technological challenges resulting from the small dimensions of heart and blood vessels as well as high heart and respiratory rates, particularly in mice, are tackled. (C) 2015 Elsevier B.V. All rights reserve

<i>In vitro</i> blood clot binding test using FibPep-ION-Micelles and negative control NCFibPep-ION-Micelles.

<p>(A) Schematic overview of fibrin-binding peptides (FibPep) conjugation to the ION-Micelles. (B) Photograph and (C) sagittal MR image of blood clots incubated with either FibPep-ION-Micelles (left) or NCFibPep-ION-Micelles (right). (D) MR signal to noise ratio of the (NC)FibPep-ION-Micelles incubated clots. (E) Third harmonic (76 kHz) MPS signal amplitude and estimated iron content of blood clots incubated with (NC)FibPep-ION-Micelles. Estimated iron content was calculated using the third harmonic MPS signal and a previously defined conversion factor for this particular batch IONs of 6.87 mAm²/g Fe. (F) Iron content of blood clots incubated with (NC)FibPep-ION-Micelles. Data represents mean ± standard deviation (n = 4).</p

Transmission electron microscopy analysis of the IONs.

<p>(A) Typical TEM micrograph of the IONs; inset shows occasional presence of a subset of particles with a smaller diameter (arrows). (B) Size distribution profile of the IONs obtained from TEM analysis of 400 nanoparticles. (C) Selected area electron diffraction (SAED) pattern acquired from IONs.</p

Schematic overview and TEM-micrograph of an ION displaying a magnetic core and a non-magnetic layer.

<p>Schematic overview and TEM-micrograph of an ION displaying a magnetic core and a non-magnetic layer.</p

Schematic overview of the (A–B) iron oxide nanoparticles and (C–D) ION-Micelle synthesis.

<p>Schematic overview of the (A–B) iron oxide nanoparticles and (C–D) ION-Micelle synthesis.</p

Analysis of ION-Micelles magnetic properties.

<p>(A) Magnetization curve of the ION-Micelles at room temperature. Inset: zoomed-in view around zero field. (B) Number-weighted particle size distribution of the ION-Micelles calculated from the magnetization curve. d_max is the diameter corresponding to the maximum of the peak. (C) MPS experimental data of the ION-Micelles, Endorem, Resovist and Sinerem plotted as magnetic moment (normalized for iron content) versus frequency.</p