Volker Herold

Measuring RF-induced currents inside implants: Impact of device configuration on MRI safety of cardiac pacemaker leads

Radiofrequency (RF)‐related heating of cardiac pacemaker leads is a serious concern in magnetic resonance imaging (MRI). Recent investigations suggest such heating to be strongly dependent on an implants position within the surrounding medium, but this issue is currently poorly understood. In this study, phantom measurements of the RF‐induced electric currents inside a pacemaker lead were performed to investigate the impact of the device position and lead configuration on the amount of MRI‐related heating at the lead tip. Seven hundred twenty device position/lead path configurations were investigated. The results show that certain configurations are associated with a highly increased risk to develop MRI‐induced heating, whereas various configurations do not show any significant heating. It was possible to precisely infer implant heating on the basis of current intensity values measured inside a pacemaker lead. Device position and lead configuration relative to the surrounding medium are crucial to the amount of RF‐induced heating in MRI. This indicates that a considerable number of implanted devices may incidentally not develop severe heating in MRI because of their specific configuration in the body. Small variations in configuration can, however, strongly increase the risk for such heating effects, meaning that hazardous situations might appear during MRI. Magn Reson Med, 2009.

In vivo time-resolved quantitative motion mapping of the murine myocardium with phase contrast MRI.

Myocardial motion of healthy mice and mice with myocardial infarction was assessed in vivo by phase contrast (PC) cine MRI. The imaging module was a segmented fast low angle shot (FLASH) sequence with velocity compensation in all three gradient directions. To accomplish additional motion encoding, the spin phase was prepared using bipolar gradient pulses, which resulted in a linear dependence between the voxel velocity and spin phase. This method provided accurate quantification of the velocity magnitude and direction of the murine myocardium at a spatial resolution of 234 μm and a temporal resolution of about 10 ms. The acquisition was EKG‐gated and the mice were anesthetized by inhalation of 1.5–4.0 vol.% isoflurane at 1.5 l/min oxygen flow. To validate the MRI measurements, an experiment with a calibrated rotating phantom was performed. Deviations between MR velocity measurements and optical assessment by a light detector were lower than 1.6%. During our study, myocardial motion velocities between 0.4 cm/s and 1.7 cm/s were determined for the healthy murine myocardium across the heart cycle. Areas with myocardial infarction were clearly segmented and showed a motion velocity which was significantly reduced. In conclusion, the method is an accurate technique for the assessment of murine myocardial motion in vivo. Magn Reson Med 49:315–321, 2003.

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. Conclusion—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.

Measurement of apparent cell radii using a multiple wave vector diffusion experiment

It had been previously shown that an idealized version of the two‐wave‐vector extension of the NMR pulsed‐field‐gradient spin echo diffusion experiment can be used to determine the apparent radius of geometries with restricted diffusion. In the present work, the feasibility of the experiment was demonstrated in an NMR imaging experiment, in which the apparent radius of axons in white matter tissue was determined. Moreover, numerical simulations have been carried out to determine the reliability of the results. For small diffusion times, the radius is systematically underestimated. Larger gradient area, finite length gradient pulses, and a statistical distribution of radii within a voxel all have a minor influence on the estimated radius. Magn Reson Med, 2009.

In vivo measurement of local aortic pulse-wave velocity in mice with MR microscopy at 17.6 tesla

Transgenic mouse models of human diseases have gained increasing importance in the pathophysiology of cardiovascular diseases (CVD). As an indirect measure of vascular stiffness, aortic pulse‐wave velocity (PWV) is an important predictor of cardiovascular risk. This study presents an MRI approach that uses a flow area method to estimate local aortic pulse‐wave velocity at different sites in the murine aorta. By simultaneously measuring the cross‐sectional area and the through‐plane velocity with a phase‐contrast CINE method, it was possible to measure average values for the PWV in the ascending and descending aorta within the range of 2.4–4.3 m/s for C57BL/6J mice (ages 2 and 8 months) and apoE‐knockout mice (age 8 months). Statistically significant differences of the mean values of the PWV of both groups could be determined. By repeating CINE measurements with a time delay of 1 ms between two subsequent data sets, an effective temporal resolution of 1000 frames/s (fps) could be achieved. Magn Reson Med, 2009.

Impact of imaging landmark on the risk of MRI‐related heating near implanted medical devices like cardiac pacemaker leads

Implanted medical devices such as cardiac pacemakers pose a potential hazard in magnetic resonance imaging. Electromagnetic fields have been shown to cause severe radio frequency‐induced tissue heating in some cases. Imaging exclusion zones have been proposed as an instrument to reduce patient risk. The purpose of this study was to further assess the impact of the imaging landmark on the risk for unintended implant heating by measuring the radio frequency‐induced electric fields in a body phantom under several imaging conditions at 1.5T. The results show that global radio frequency‐induced coupling is highest with the torso centered along the superior–inferior direction of the transmit coil. The induced E‐fields inside the body shift when changing body positioning, reducing both global and local radio frequency coupling if body and/or conductive implant are moved out from the transmit coil center along the z‐direction. Adequate selection of magnetic resonance imaging landmark can significantly reduce potential hazards in patients with implanted medical devices. Magn Reson Med, 2010.

In vivo quantitative three-dimensional motion mapping of the murine myocardium with PC-MRI at 17.6 T

This work presents a method that allows for the assessment of 3D murine myocardial motion in vivo at microscopic resolution. Phase‐contrast (PC) magnetic resonance imaging (MRI) at 17.6 T was applied to map myocardial motion in healthy mice along three gradient directions. High‐resolution velocity maps were acquired at three different levels in the murine myocardium with an in‐plane resolution of 98 μm, a slice thickness of 0.6 mm, and a temporal resolution of 6 ms. The applied PC‐MRI method was validated with phantom experiments that confirmed the correctness of the method with deviations of <1.7%. Myocardial in‐plane velocities between 0.5 cm/s and 2.2 cm/s were determined for the healthy murine myocardium. Through‐plane velocities of 0.1–0.83 cm/s were measured. Velocity data was also used to calculate the myocardial twist angle during systole at different slices in the short‐axis view. Magn Reson Med, 2006.

Targeting P-Selectin by Gallium-68–Labeled Fucoidan Positron Emission Tomography for Noninvasive Characterization of Vulnerable Plaques Correlation With In Vivo 17.6T MRI

Objective— Nuclear imaging of active plaques still remains challenging. Advanced atherosclerotic plaques have a strong expression of P-selectin by the endothelium overlying active atherosclerotic plaques, but not on the endothelium overlying inactive fibrous plaques. We proposed a new approach for noninvasive in vivo characterization of P-selectin on active plaques based on 68Ga-Fucoidan, which is a polysaccharidic ligand of P-selectin with a nanomolar affinity. Approach and Results— 68Ga-Fucoidan was tested for its potential to discriminate vulnerable plaques on apolipoprotein E–deficient mice receiving a high cholesterol diet by positron emission tomography and in correlation with 17.6T MRI. Furthermore, 68Ga-Fucoidan was evaluated on endothelial cells in vitro and ex vivo on active plaques using autoradiography. The cellular uptake rate was increased ≈2-fold by lipopolysaccharide induction. Interestingly, on autoradiography, more intensive tracer accumulation at active plaques with thin fibrous caps and high-density foam cells were observed in comparison with a weaker focal uptake in inactive fibrous plaque segments (R=1.7±0.3; P<0.05) and fatty streaks (R=2.4±0.4; P<0.01). Strong uptake of radiotracer colocalized with increased P-selectin expression and high-density macrophage. Focal vascular uptake (mean of target to background ratio=5.1±0.8) of 68Ga-Fucoidan was detected in all apolipoprotein E–deficient mice. Anatomic structures of plaque were confirmed by 17.6T MRI. The autoradiography showed a good agreement of 68Ga-Fucoidan uptake with positron emission tomography. Conclusions— Our data suggest that 68Ga-Fucoidan represents a versatile imaging biomarker for P-selectin with the potential to specifically detect P-selectin expression using positron emission tomography and to discriminate vulnerable plaques in vivo.

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.

In vivo comparison of atherosclerotic plaque progression with vessel wall strain and blood flow velocity in apoE −/− mice with MR microscopy at 17.6 T

ObjectAt present, in vivo plaque characterization in mice by MRI is typically limited to the visualization of vascular lesions with no accompanying analysis of vessel wall function. The aim of this study was to analyze the influence of atherosclerotic plaque development on the morphological and mechanical characteristics of the aortic vessel wall in a pre-clinical murine model of atherosclerosis.Materials and methodsGroups of apolipoprotein E-deficient (apoE−/−) and C57BL/6J control mice fed a high-fat diet were monitored over a 12-week time period by high-field MRI. Multi-Slice-Multi-Spin-Echo and Phase-Contrast MRI sequences were employed to track changes to aortic vessel wall area, blood flow velocity and distensibility.ResultsAfter 6- and 12-weeks, significant changes in vessel wall area and circumferential strain were detected in the apoE−/− mice relative to the control animals. Blood flow velocity and intravascular lumen remained unchanged in both groups, findings that are in agreement with the theory of positive remodeling of the ascending aorta during plaque progression.ConclusionThis study has demonstrated the application of high-field MRI for characterizing the temporal progression of morphological and mechanical changes to murine aortic vasculature associated with atherosclerotic lesion development.