Visualization of vascular inflammation in the atherosclerotic mouse by ultrasmall superparamagnetic iron oxide vascular cell adhesion molecule-1-specific nanoparticles.

OBJECTIVE: Noninvasive imaging of atherosclerosis remains challenging in clinical applications. Here, we applied noninvasive molecular imaging to detect vascular cell adhesion molecule-1 in early and advanced atherosclerotic lesions of apolipoprotein E-deficient mice. METHODS AND RESULTS: Ultrasmall superparamagnetic iron oxide particles functionalized with (P03011) or without (P3007) vascular cell adhesion molecule-1-binding peptide were visualized by ultra high-field (17.6 T) magnetic resonance. Injection of P03011 resulted in a marked signal loss in the aortic root of apolipoprotein E-deficient mice fed a Western diet for 8 and 26 weeks in vivo and ex vivo, compared with preinjection measurements, P3007-injected mice, and P03011- or P3007-injected age-matched C57BL/6 controls. Histological analyses revealed iron accumulations in the intima, in colocalization with vascular cell adhesion molecule-1-expressing macrophages and endothelial cells. Coherent anti-Stokes Raman scattering microscopy demonstrated iron signals in the intima and media of the aortic root in the P03011-injected but not untreated apolipoprotein E-deficient mice, localized to macrophages, luminal endothelial-like cells, and medial regions containing smooth muscle cells. Electron microscopy confirmed iron particles enclosed in endothelial cells and in the vicinity of smooth muscle cells. CONCLUSIONS: Using a combination of innovative imaging modalities, in this study, we demonstrate the feasibility of applying P03011 as a contrast agent for imaging of atherosclerosis.

An 8 channel parallel transmit system with current sensor feedback for MRI-guided interventional applications.

Background.Parallel transmit (pTx) has introduced many benefits to magnetic resonance imaging (MRI) with regard to decreased specific absorption rates and improved transmit field homogeneity, of particular importance in applications at higher magnetic field strengths. PTx has also been proposed as a solution to mitigating dangerous RF induced heating of elongated conductive devices such as those used in cardiac interventions. In this work we present a system that can augment a conventional scanner with pTx, in particular for use in interventional MRI for guidewire safety, by adjusting the amplitude and phase of each channel right before the start of the imaging pulses.Methods.The pTx system was designed to work in-line with a 1.5 T MRI while the RF synthesis and imaging control was maintained on the host MR scanner. The add-on pTx system relies on the RF transmit signal, unblanking pulse, and a protocol driven trigger from the scanner. The RF transmit was split into multiple fully modulated transmit signals to drive an array of custom transceiver coils. The performance of the 8-channel implementation was tested with regards to active and real-time control of RF induced currents on a standard guidewire, heating mitigation tests, and anatomical imaging in sheep.Results. The pTx system was intended to update RF shims in real-time and it was demonstrated that the safe RF shim could be determined while the guidewire is moved. The anatomical imaging demonstrated that cardiac anatomy and neighbouring superficial structures could be fully characterized with the pTx system inline.Conclusion.We have presented the design and performance of a real-time feedback control pTx system capable of adding such capabilities to a conventional MRI with the focus of guidewire imaging in cardiac interventional MRI applications.

In vivo T2* weighted MRI visualizes cardiac lesions in murine models of acute and chronic viral myocarditis.

OBJECTIVE: Acute and chronic forms of myocarditis are mainly induced by virus infections. As a consequence of myocardial damage and inflammation dilated cardiomyopathy and chronic heart failure may develop. The gold standard for the diagnosis of myocarditis is endomyocardial biopsies which are required to determine the etiopathogenesis of cardiac inflammatory processes. However, new non-invasive MRI techniques hold great potential in visualizing cardiac non-ischemic inflammatory lesions at high spatial resolution, which could improve the investigation of the pathophysiology of viral myocarditis. RESULTS: Here we present the discovery of a novel endogenous T2* MRI contrast of myocardial lesions in murine models of acute and chronic CVB3 myocarditis. The evaluation of infected hearts ex vivo and in vivo by 3D T2w and T2*w MRI allowed direct localization of virus-induced myocardial lesions without any MRI tracer or contrast agent. T2*w weighted MRI is able to detect both small cardiac lesions of acute myocarditis and larger necrotic areas at later stages of chronic myocarditis, which was confirmed by spatial correlation of MRI hypointensity in myocardium with myocardial lesions histologically. Additional in vivo and ex vivo MRI analysis proved that the contrast mechanism was due to a strong paramagnetic tissue alteration in the vicinity of myocardial lesions, effectively pointing towards iron deposits as the primary contributor of contrast. The evaluation of the biological origin of the MR contrast by specific histological staining and transmission electron microscopy revealed that impaired iron metabolism primarily in mitochondria caused iron deposits within necrotic myocytes, which induces strong magnetic susceptibility in myocardial lesions and results in strong T2* contrast. CONCLUSION: This T2*w MRI technique provides a fast and sensitive diagnostic tool to determine the patterns and the severity of acute and chronic enteroviral myocarditis and the precise localization of tissue damage free of MR contrast agents.

Comparison of multiple quantitative MRI parameters for characterization of the goat cartilage in an ongoing osteoarthritis: dGEMRIC, T1ρ and sodium.

RATIONALE AND OBJECTIVES: Osteoarthritis (OA) is a degenerative joint disease leading to cartilage deterioration by loss of matrix, fibrillation, formation of fissures, and ultimately complete loss of the cartilage surface. Here, three magnetic resonance imaging (MRI) techniques, dGEMRIC (delayed Gadolinium enhanced MRI of cartilage; dG1=T1,post; dG2=1/T1,post-1/T1,pre), T1ρ,and sodium MRI, are compared in a preclinical in vivo study to evaluate the differences in their potential for cartilage characterization and to establish an examination protocol for a following clinical study. MATERIALS AND METHODS: OA was induced in 12 caprine knees (6 control, 6 therapy). Adipose derived stem cells were injected afterwards as a treatment. The animals were examined healthy, 3 and 16 weeks postoperatively with all three MRI methods. Using statistical analysis, the OA development and the degree of correlation between the different MRI methods were determined. RESULTS: A strong correlation was observed between the dGEMRIC indices dG1 and dG2 (r=-0.87) which differ only in considering or not considering the T1 baseline. Moderate correlations were found between T1ρ and dG1 (r=0.55), T1ρ and dG2 (r=0.47) and at last, sodium and dG1 (r=0.45). The correlations found in this study match to the biomarkers which the methods are sensitive to. CONCLUSION: Even though the goat cartilage is significantly thinner than the human cartilage and even more in a degenerated cartilage, all three methods were able to characterize the cartilage over the whole period of time during an ongoing OA. Due to measurement and post processing optimizations, as well as the correlations detected in this work, the overall measurement time in future goat studies can be minimized. Moreover, an examination protocol for characterizing the cartilage in a clinical study was established.

Optimization and comparison of two practical dual-tuned birdcage configurations for quantitative assessment of articular cartilage with sodium magnetic resonance imaging.

BACKGROUND: In this study, two practical dual-tuned birdcage configurations for quantitative assessment of articular cartilage with sodium magnetic resonance imaging (MRI) were designed and compared. METHODS: Two 1.5 T dual-tuned birdcages, a four-ring birdcage (FRB) and an alternating rungs birdcage (ARB), were built and then characterized by bench and MRI measurements. The relative uniformity (RU) and the efficiency of the coils were compared using (23)Na and (1)H B1 maps. In vivo images of a volunteer were acquired. RESULTS: Bench measurements showed matching and decoupling coefficients of the quadrature channels lower than -20 dB. The RUs and 180° pulse amplitudes of the FRB/ARB were determined as: (1)H RU =94.4/74.4%, (23)Na RU =95.2/93.6%, (1)H 180° pulse amplitude =69.2/75.4 V and (23)Na 180° pulse amplitude =45.1/45.9 V. The in vivo (23)Na images acquired with the FRB show a signal-to-noise ratio (SNR) of 6 to 14 in the cartilage. CONCLUSIONS: Due to its superior (1)H homogeneity and efficiency and its slightly better (23)Na homogeneity, the FRB is the overall preferred coil for the given requirements of this study. The achieved in vivo SNR is adequate for quantitative (23)Na and high resolution (1)H imaging.

Local arterial stiffening assessed by MRI precedes atherosclerotic plaque formation.

BACKGROUND: Atherosclerosis is known to impair vascular function and cause vascular stiffening. The aim of this study was to evaluate the potential predictive role of vascular stiffening in the early detection of atherosclerosis. Therefore, we investigated the time course of early functional and morphological alterations of the vessel wall in a murine atherosclerosis model. Because initial lesions are distributed inhomogeneously in early-stage atherosclerosis, MR microscopy was performed to measure vascular elasticity locally, specifically the local pulse wave velocity and the arterial wall thickness. METHODS AND RESULTS: Local pulse wave velocity and the mean arterial wall thickness were determined in the ascending and the abdominal aortae of ApoE(-/-) and wild-type mice. In vivo MRI revealed that baseline pulse wave velocity and morphology were similar in 6-week-old ApoE(-/-) and WT mice, whereas at the age of 18 weeks, local pulse wave velocity was significantly elevated in ApoE(-/-) mice. Significantly increased vessel wall thickness was not found in ApoE(-/-) mice until the age of 30 weeks. Histological analysis of the aortae of ApoE(-/-) and WT mice showed that increased pulse wave velocity coincided with the fragmentation of the elastic laminae in the arterial wall, which is hypothesized to induce early vascular stiffening and may be promoted by macrophage-mediated matrix degradation. CONCLUSIONS: We newly report that the assessment of local pulse wave velocity via MRI provides early information about the local progression of atherosclerosis before macroscopic alterations of the vessel wall occur.