Inductively Coupled Intraoral Flexible Coil for Increased Visibility of Dental Root Canals in Magnetic Resonance Imaging.

OBJECTIVES: Accurate visualization of dental root canals is vital for the correct diagnosis and subsequent treatment. This work assesses the improvement of a dedicated new coil for dental magnetic resonance imaging (MRI) in comparison to conventional ones in terms of signal-to-noise ratio (SNR) and visibility. MATERIALS AND METHODS: A newly developed intraoral flexible coil was used to display dental roots with MRI, and it provides improved sensitivity with a loop design and size adjusted to a single tooth anatomy. Ex vivo and in vivo measurements were performed on a 3 T clinical MR system, and results were compared with conventional head and surface coil images. Additional comparison was performed with a modified fast spin echo sequence and a constructive interference in steady-state sequence. RESULTS: Ex vivo, an SNR gain of 6.3 could be achieved with the intraoral flexible coil setup, and higher visibility down to 200 µm was possible, whereas the external loop coil is limited to 400 µm. In vivo measurements in a volunteer resulted in an SNR gain of up to 4.5 with an improved delineation of the root canals, especially for the branch tissue splitting of the mesial root canal into mesial-buccal and mesial-lingual. CONCLUSIONS: In summary, we showed the feasibility of implementing a wireless coil approach with readily available dental practice materials for sealing and placement. Highly improved MRI scans can be acquired within clinically feasible scan times, and this might provide additional medical findings to supplement available x-ray images.

Molecular magnetic resonance imaging of activated platelets allows noninvasive detection of early myocarditis in mice.

MRI sensitivity for diagnosis and localization of early myocarditis is limited, although it is of central clinical interest. The aim of this project was to test a contrast agent targeting activated platelets consisting of microparticles of iron oxide (MPIO) conjugated to a single-chain antibody directed against ligand-induced binding sites (LIBS) of activated glycoprotein IIb/IIIa (= LIBS-MPIO). Myocarditis was induced by subcutaneous injection of an emulsion of porcine cardiac myosin and complete Freund's adjuvant in mice. 3D 7 T in-vivo MRI showed focal signal effects in LIBS-MPIO injected mice 2 days after induction of myocarditis, whereas in control-MPIO injected mice no signal was detectable. Histology confirmed CD41-positive staining, indicating platelet involvement in myocarditis in mice as well as in human specimens with significantly higher LIBS-MPIO binding compared to control-MPIO in both species. Quantification of the myocardial MRI signal confirmed a signal decrease after LIBS-MPIO injection and significant less signal in comparison to control-MPIO injection. These data show, that platelets are involved in inflammation during the course of myocarditis in mice and humans. They can be imaged non-invasively with LIBS-MPIO by molecular MRI at an early time point of the inflammation in mice, which is a valuable approach for preclinical models and of interest for both diagnostic and prognostic purposes.

Analysis of accelerated 4D flow MRI in the murine aorta by radial acquisition and compressed sensing reconstruction.

Preclinical 4D flow MRI remains challenging and is restricted for parallel imaging acceleration due to the limited number of available receive channels. A radial acquisition with combined parallel imaging and temporal compressed sensing reconstruction was implemented to achieve accelerated preclinical 4D flow MRI. In order to increase the accuracy of the measured velocities, a quantitative evaluation of different temporal regularization weights for the compressed sensing reconstruction based on velocity instead of magnitude data is performed. A 3D radial retrospectively triggered phase contrast sequence with a combined parallel imaging and compressed sensing reconstruction with temporal regularization was developed. It was validated in a phantom and in vivo (C57BL/6 J mice), against an established fully sampled Cartesian sequence. Different undersampling factors (USFs [12, 15, 20, 30, 60]) were evaluated, and the effect of undersampling was analyzed in detail for magnitude and velocity data. Temporal regularization weights λ were evaluated for different USFs. Acceleration factors of up to 20 compared with full Nyquist sampling were achieved. The peak flow differences compared with the Cartesian measurement were the following: USF 12, 3.38%; USF 15, 4.68%; USF 20, 0.95%. The combination of 3D radial center-out trajectories and compressed sensing reconstruction is robust against motion and flow artifacts and can significantly reduce measurement time to 30 min at a resolution of 180 µm3 . Concisely, radial acquisition with combined compressed sensing and parallel imaging proved to be an excellent method for analyzing complex flow patterns in mice.

Genotyping of circulating cell-free DNA enables noninvasive tumor detection in myxoid liposarcomas.

Soft tissue sarcomas (STS) are rare tumors of mesenchymal origin. About 50% of patients with STS experience relapse and more than 30% will die within 10 years after diagnosis. In this study we investigated circulating free DNA (cfDNA) and tumor-specific genetic alterations therein (circulating tumor DNA, ctDNA) as diagnostic biomarkers. Plasma concentrations and fragmentation of cfDNA was analyzed with quantitative PCR. Patients with STS (n = 64) had significantly higher plasma concentrations and increased fragmentation of cfDNA when compared to patients in complete remission (n = 19) and healthy controls (n = 41) (p < 0.01 and p < 0.001). Due to overlapping values between patients with STS and controls, the sensitivity and specificity of these assays is limited. Sensitive assays to detect genomic alterations in cfDNA of synovial sarcomas (t(X;18)), myxoid liposarcomas (t(12;16) and TERT C228T promoter mutation) and well-differentiated/de-differentiated liposarcomas (MDM2 amplifications) were established. ctDNA was quantified in nine liposarcoma patients during the course of their treatment. Levels of breakpoint t(12;16) and TERT C228T ctDNA correlated with the clinical course and tumor burden in patients with myxoid liposarcomas (n = 4). ctDNA could detect minimal residual disease and tumor recurrence. In contrast, detection of MDM2 amplifications was not sensitive enough to detect tumors in patients with well-differentiated/de-differentiated liposarcomas (n = 5). Genotyping of cfDNA for tumor specific genetic alterations is a feasible and promising approach for monitoring tumor activity in patients with myxoid liposarcomas. Detection of ctDNA during follow-up examinations despite negative standard imaging studies might warrant more sensitive imaging (e.g. PET-CT) or closer follow-up intervals to timely localize and treat recurrences.

In vivo 13C-MRI using SAMBADENA.

Magnetic Resonance Imaging (MRI) is a powerful imaging tool but suffers from a low sensitivity that severely limits its use for detecting metabolism in vivo. Hyperpolarization (HP) methods have demonstrated MRI signal enhancement by several orders of magnitude, enabling the detection of metabolism with a sensitivity that was hitherto inaccessible. While it holds great promise, HP is typically relatively slow (hours), expensive (million $, €) and requires a dedicated device ("polarizer"). Recently, we introduced a new method that creates HP tracers without an external polarizer but within the MR-system itself based on parahydrogen induced polarization (PHIP): Synthesis Amid the Magnet Bore Allows Dramatically Enhanced Nuclear Alignment (SAMBADENA). To date, this method is the simplest and least cost-intensive method for hyperpolarized 13C-MRI. HP of P13C > 20% was demonstrated for 5mM tracer solutions previously. Here, we present a setup and procedure that enabled the first in vivo application of SAMBADENA: Within seconds, a hyperpolarized angiography tracer was produced and injected into an adult mouse. Subsequently, fast 13C-MRI was acquired which exhibited the vena cava, aorta and femoral arteries of the rodent. This first SAMBADENA in vivo 13C-angiography demonstrates the potential of the method as a fast, simple, low-cost alternative to produce HP-tracers to unlock the vast but hidden powers of MRI.

Preclinical 4D-flow magnetic resonance phase contrast imaging of the murine aortic arch.

PURPOSE: Cardiovascular diseases remain the number one death cause worldwide. Preclinical 4D flow phase contrast magnetic resonance imaging can provide substantial insights in the analysis of aortic pathophysiologies in various animal models. These insights may allow a better understanding of pathophysiologies, therapy monitoring, and can possibly be translated to humans. This study provides a framework to acquire the velocity field within the aortic arch. It analyses important flow values at different locations within the aortic arch. Imaging parameters with high temporal and spatial resolution are provided, that still allow combining this time-consuming method with other necessary imaging-protocols. METHODS: A new setup was established where a prospectively gated 4D phase contrast sequence is combined with a highly sensitive cryogenic coil on a preclinical magnetic resonance scanner. The sequence was redesigned to maintain a close to steady state condition of the longitudinal magnetization and hence to overcome steady state artifacts. Imaging parameters were optimized to provide high spatial and temporal resolution. Pathline visualizations were generated from the acquired velocity data in order to display complex flow patterns. RESULTS: Our setup allows data acquisition with at least two times the rate than that of previous publications based on Cartesian encoding, at an improved image quality. The "steady state" sequence reduces observed artifacts and provides uniform image intensity over the heart cycle. This made possible quantification of blood speed and wall shear stress (WSS) within the aorta and its branches. The highest velocities were observed in the ascending aorta with 137.5 ± 8 cm/s. Peak velocity values in the Brachiocephalic trunk were 57 ± 12 cm/s. Quantification showed that the peak flow occurs around 20 ms post R-wave in the ascending aorta. The highest mean axial wall shear stress was observed in the analysis plane between the left common carotid artery (LCCA) and the left subclavian artery. A stable image quality allows visualizing complex flow patterns by means of streamlines and for the first time, to the best of our knowledge, pathline visualizations from 4D flow MRI in mice. CONCLUSION: The described setup allows analyzing pathophysiologies in mouse models of cardiovascular diseases in the aorta and its branches with better image quality and higher spatial and temporal resolution than previous Cartesian publications. Pathlines provide an advanced analysis of complex flow patterns in the murine aorta. An imaging protocol is provided that offers the possibility to acquire the aortic arch at sufficiently high resolution in less than one hour. This allows the combination of the flow assessment with other multifunctional imaging protocols.

Dual-contrast molecular imaging allows noninvasive characterization of myocardial ischemia/reperfusion injury after coronary vessel occlusion in mice by magnetic resonance imaging.

BACKGROUND: Inflammation and myocardial necrosis play important roles in ischemia/reperfusion injury after coronary artery occlusion and recanalization. The detection of inflammatory activity and the extent of myocardial necrosis itself are of great clinical and prognostic interest. We developed a dual, noninvasive imaging approach using molecular magnetic resonance imaging in an in vivo mouse model of myocardial ischemia and reperfusion. METHODS AND RESULTS: Ischemia/reperfusion injury was induced in 10-week-old C57BL/6N mice by temporary ligation of the left anterior descending coronary artery. Activated platelets were targeted with a contrast agent consisting of microparticles of iron oxide (MPIOs) conjugated to a single-chain antibody directed against a ligand-induced binding site (LIBS) on activated glycoprotein IIb/IIIa (LIBS-MPIOs). After injection and imaging of LIBS-MPIOs, late gadolinium enhancement was used to depict myocardial necrosis; these imaging experiments were also performed in P2Y12 (-/-) mice. All imaging results were correlated to immunohistochemistry findings. Activated platelets were detectable by magnetic resonance imaging via a significant signal effect caused by LIBS-MPIOs in the area of left anterior descending coronary artery occlusion 2 hours after reperfusion. In parallel, late gadolinium enhancement identified the extent of myocardial necrosis. Immunohistochemistry confirmed that LIBS-MPIOs bound significantly to microthrombi in reperfused myocardium. Only background binding was found in P2Y12 (-/-) mice. CONCLUSIONS: Dual molecular imaging of myocardial ischemia/reperfusion injury allows characterization of platelet-driven inflammation by LIBS-MPIOs and myocardial necrosis by late gadolinium enhancement. This noninvasive imaging strategy is of clinical interest for both diagnostic and prognostic purposes and highlights the potential of molecular magnetic resonance imaging for characterizing ischemia/reperfusion injury.