To compare magnetic resonance elastography (MRE) with ventricular pressure changes in an animal model. Three pigs of different cardiac physiology (weight, 25 to 53 kg; heart rate, 61 to 93 bpm; left ventricular [LV] end-diastolic volume, 35 to 70 ml) were subjected to invasive LV pressure measurement by catheter and noninvasive cardiac MRE. Cardiac MRE was performed in a short-axis view of the heart and applying a 48.3-Hz shear-wave stimulus. Relative changes in LV-shear wave amplitudes during the cardiac cycle were analyzed. Correlation coefficients between wave amplitudes and LV pressure as well as between wave amplitudes and LV diameter were determined. A relationship between MRE and LV pressure was observed in all three animals (R² ≥ 0.76). No correlation was observed between MRE and LV diameter (R² ≤ 0.15). Instead, shear wave amplitudes decreased 102 ± 58 ms earlier than LV diameters at systole and amplitudes increased 175 ± 40 ms before LV dilatation at diastole. Amplitude ratios between diastole and systole ranged from 2.0 to 2.8, corresponding to LV pressure differences of 60 to 73 mmHg. Externally induced shear waves provide information reflecting intraventricular pressure changes which, if substantiated in further experiments, has potential to make cardiac MRE a unique noninvasive imaging modality for measuring pressure-volume function of the heart.

Non-invasive quantification of functional parameters of the cardiovascular system, in particular the heart, remains very challenging with current imaging techniques. This aspect is mainly due to the fact, that the spatiotemporal resolution of current imaging methods, such as Magnetic Resonance Imaging (MRI) or Positron Emission Tomography (PET), does not offer the desired data repetition rates in the context of real-time data acquisition and thus, can cause artifacts and misinterpretations in accelerated data acquisition approaches. We present a fast non-invasive and quantitative dual-modal in situ cardiovascular assessment using a hybrid imaging system which combines the new imaging modality Magnetic Particle Imaging (MPI) and MRI. This pre-clinical hybrid imaging system provides either a 0:5T homogeneous B0 field for MRI or a 2:2T=m gradient field featuring a Field- Free-Point for MPI. A comprehensive coil system allows in both imaging modes for spatial encoding, signal excitation and reception. In this work, 3-dimensional anatomical information acquired with MRI is combined with in situ sequentially acquired time-resolved 3D (i.e. 3D+t) MPI bolus tracking of superparamagnetic iron oxide nanoparticles. MPI data were acquired during a 21μl (40μmol(Fe)=kgBW) bolus tail vein injection under free-breathing with an ungated and non-triggered MPI scan with a repetition rate of 46 volumes per seconds. We successfully determined quantitative hemodynamics as 3D+t velocity vector estimations of a beating rat’s heart by analyzing 3 seconds of 3D+t MPI image data. The used hybrid system allows for MR-based MPI Field-of-View planning and cardiac crosssectional anatomy analysis, precise co-registration of dualmodal datasets, as well as for MPI-based hemodynamic functional analysis using an optical flow technique. We present the first in-vivo results of a new methodology, allowing for fast, non-invasive, quantitative and in situ hybrid cardiovascular assessment, showing its potential for future clinical applications.

VSOP-C184 at a dose of 0.045 mmol Fe/kg has been shown to be an efficient blood pool contrast medium for equilibrium magnetic resonance angiography (MRA) that can be administered as a bolus. The present study was performed to determine whether VSOP-C184 is also suitable for first-pass MRA. Fifteen MRA examinations at 1.5 T were performed in minipigs using a fast 3D fast low-angle shot (FLASH) sequence (repetition time = 4.5 ms, echo time = 1.7 ms, excitation angle = 25°, matrix 256, body phased-array coil). The citrate-stabilized iron oxide preparation VSOP-C184 was investigated (total particle diameter: 7.0 ± 0.15 nm; core size: 4 nm) and compared with gadopentetate dimeglumine (Gd-DTPA). The following doses were tested: VSOP-C184: 0.015, 0.025, and 0.035 mmol Fe/kg; Gd-DTPA: 0.1 and 0.2 mmol Gd/kg; n = 3 examinations/dose. Data were analyzed quantitatively (signal enhancement (ENH) and vessel edge definition (VED)) and qualitatively. First-pass MRA using the 3 doses of VSOP-C184 yielded the following ENH: aorta: 9.4 ± 2.6; 12.31 ± 1.2; 16.53 ± 1.7; renal arteries: 7.6 ± 2.2; 9.9 ± 1.0; 13.2 ± 0.5. The values for the 2 doses of Gd-DTPA were aorta: 12.9 ± 1.0; 16.8 ± 2.2; renal arteries: 11.2 ± 1.23; 11.3 ± 1.7. VED for the 3 doses of VSOP-C184 was aorta: 106.3 ± 31.0; 135.3 ± 58.8; 141.3 ± 71.0; renal arteries: 102.2 ± 24.3; 146.8 ± 63.0; 126.9 ± 37.6 and for the 2 doses of Gd-DTPA, aorta: 157.2 ± 47.8; 164.2 ± 36.8; renal arteries: 165.9 ± 30.4; 170.3 ± 38.2 respectively. The differences between VSOP-C184 and Gd-DTPA are clinically not relevant and statistically not significant (p ≥ .05). Qualitative evaluation of image quality, contrast, and delineation of vessels showed the results obtained with VSOP-C184 at doses of 0.025 and 0.035 mmol Fe/kg to be similar to those of Gd-DTPA at 0.1 and 0.2 mmol Gd/kg. VSOP-C184 is suitable for first-pass MRA at doses of 0.025 and 0.035 mmol Fe/kg and thus, in addition to its blood pool characteristics, allows for selective visualization of the arteries without interfering venous signal.

Background: Gadopentate dimeglumine (Gd-DTPA) enhanced magnetic resonance imaging (MRI) is widely applied for the visualization of blood brain barrier (BBB) breakdown in multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). Recently, the potential of magnetic nanoparticles to detect macrophage infiltration by MRI was demonstrated. We here investigated a new class of very small superparamagnetic iron oxide particles (VSOP) as novel contrast medium in murine adoptive-transfer EAE. Methods: EAE was induced in 17 mice via transfer of proteolipid protein specific T cells. MR images were obtained before and after application of Gd-DTPA and VSOP on a 7 Tesla rodent MR scanner. The enhancement pattern of the two contrast agents was compared, and correlated to histology, including Prussian Blue staining for VSOP detection and immunofluorescent staining against IBA-1 to identify macrophages/microglia. Results: Both contrast media depicted BBB breakdown in 42 lesions, although differing in plaques appearances and shapes. Furthermore, 13 lesions could be exclusively visualized by VSOP. In the subsequent histological analysis, VSOP was localized to microglia/macrophages, and also diffusely dispersed within the extracellular matrix. Conclusion: VSOP showed a higher sensitivity in detecting BBB alterations compared to Gd-DTPA enhanced MRI, providing complementary information of macrophage/microglia activity in inflammatory plaques that has not been visualized by conventional means.

To compare a superparamagnetic iron oxide (SPIO), VSOP-C184, with a gadopentetate dimeglumine with regard to signal-enhancing effects on T1-weighted dynamic magnetic resonance (MR) images and with another SPIO contrast medium with regard to signal-reducing effects on delayed T2-weighted MR images. All experiments were approved by the responsible Animal Care Committee. Twenty rabbits (five for each contrast agent and dose) implanted with VX-2 carcinoma were imaged at 1.5 T. VSOP-C184 at 0.015 and 0.025 mmol Fe/kg was compared with gadopentetate dimeglumine at 0.15 mmol Gd/kg and ferucarbotran at 0.015 mmol Fe/kg. The imaging protocol comprised a T1-weighted dynamic gradient-echo (GRE) MR before injection and at 6-second intervals for up to 42 seconds after injection and a T2-weighted turbo spin-echo MR before and 5 minutes after injection. Images were evaluated quantitatively, and contrast media were compared by using nonparametric analysis of variance. At dynamic T1-weighted GRE MR imaging with 0.015-mmol Fe/kg VSOP-C184, 0.025-mmol Fe/kg VSOP-C184, gadopentetate dimeglumine, and ferucarbotran, the median peak contrast-to-noise ratio (CNR) was 20.7 (25th percentile, 16.3; 75th percentile, 22.6), 24.2 (25th percentile, 19.3; 75th percentile, 28.5), 16.4 (25th percentile, 13.7; 75th percentile, 20.3), and 14.0 (25th percentile, 11.4; 75th percentile, 16.8), respectively. Both doses of VSOP-C184 yielded significantly higher CNR (P < .05) than the other two agents. At T2-weighted turbo spin-echo imaging with 0.015-mmol Fe/kg VSOP-C184, 0.025-mmol Fe/kg VSOP-C184, gadopentetate dimeglumine, and ferucarbotran, the median CNR was 15.0 (25th percentile, 13.4; 75th percentile, 21.3), 15.7 (25th percentile, 14.5; 75th percentile, 19.8), 11.3 (25th percentile, 8.2; 75th percentile, 12.2), and 15.7 (25th percentile, 12.5; 75th percentile, 22.4), respectively. There was no significant difference between VSOP-C184 and ferucarbotran; both had a significantly higher CNR than did gadopentetate dimeglumine. VSOP-C184 produces higher liver-to-tumor contrast at dynamic T1-weighted imaging than does gadopentetate dimeglumine; at delayed T2-weighted imaging, the contrast is comparable to that achieved with ferucarbotran.

Magnetic particle imaging (MPI) is a new imaging technique that detects the spatial distribution of magnetic nanoparticles (MNP) with the option of high temporal resolution. MPI relies on particular MNP as tracers with tailored characteristics for improvement of sensitivity and image resolution. For this reason, we developed optimized multicore particles (MCP 3) made by coprecipitation via synthesis of green rust and subsequent oxidation to iron oxide cores consisting of a magnetite/maghemite mixed phase. MCP 3 shows high saturation magnetization close to that of bulk maghemite and provides excellent magnetic particle spectroscopy properties which are superior to Resovist^® and any other up to now published MPI tracers made by coprecipitation. To evaluate the MPI characteristics of MCP 3 two kinds of tube phantoms were prepared and investigated to assess sensitivity, spatial resolution, artifact severity, and selectivity. Resovist^® was used as standard of comparison. For image reconstruction, the regularization factor was optimized, and the resulting images were investigated in terms of quantifying of volumes and iron content. Our results demonstrate the superiority of MCP 3 over Resovist^® for all investigated MPI characteristics and suggest that MCP 3 is promising for future experimental in vivo studies.