iMPI: portable human-sized magnetic particle imaging scanner for real-time endovascular interventions.

Minimally invasive endovascular interventions have become an important tool for the treatment of cardiovascular diseases such as ischemic heart disease, peripheral artery disease, and stroke. X-ray fluoroscopy and digital subtraction angiography are used to precisely guide these procedures, but they are associated with radiation exposure for patients and clinical staff. Magnetic Particle Imaging (MPI) is an emerging imaging technology using time-varying magnetic fields combined with magnetic nanoparticle tracers for fast and highly sensitive imaging. In recent years, basic experiments have shown that MPI has great potential for cardiovascular applications. However, commercially available MPI scanners were too large and expensive and had a small field of view (FOV) designed for rodents, which limited further translational research. The first human-sized MPI scanner designed specifically for brain imaging showed promising results but had limitations in gradient strength, acquisition time and portability. Here, we present a portable interventional MPI (iMPI) system dedicated for real-time endovascular interventions free of ionizing radiation. It uses a novel field generator approach with a very large FOV and an application-oriented open design enabling hybrid approaches with conventional X-ray-based angiography. The feasibility of a real-time iMPI-guided percutaneous transluminal angioplasty (PTA) is shown in a realistic dynamic human-sized leg model.

Dorsal Root Ganglion Volumetry by MR Gangliography.

BACKGROUND AND PURPOSE: Dorsal root ganglion MR imaging (MR gangliography) is increasingly gaining clinical-scientific relevance. However, dorsal root ganglion morphometry by MR imaging is typically performed under the assumption of ellipsoid geometry, which remains to be validated. MATERIALS AND METHODS: Sixty-four healthy volunteers (37 [57.8%] men; mean age, 31.5 [SD, 8.3] years) underwent MR gangliography of the bilateral L4-S2 levels (3D-T2WI TSE spectral attenuated inversion recovery-sampling perfection with application-optimized contrasts by using different flip angle evolution, isotropic voxels = 1.1 mm³, TE = 301 ms). Ground truth dorsal root ganglion volumes were bilaterally determined for 96 dorsal root ganglia (derivation cohort) by expert manual 3D segmentation by 3 independent raters. These ground truth dorsal root ganglion volumes were then compared with geometric ellipsoid dorsal root ganglion approximations as commonly practiced for dorsal root ganglion morphometry. On the basis of the deviations from ellipsoid geometry, improved volume estimation could be derived and was finally applied to a large human validation cohort (510 dorsal root ganglia). RESULTS: Commonly used equations of ellipsoid geometry underestimate true dorsal root ganglion volume by large degrees (factor = 0.42-0.63). Ground truth segmentation enabled substantially optimizing dorsal root ganglion geometric approximation using its principal axes lengths by deriving the dorsal root ganglion volume term of [Formula: see text]. Using this optimization, the mean volumes of 510 lumbosacral healthy dorsal root ganglia were as follows: L4: 211.3 (SD, 52.5) mm³, L5: 290.7 (SD, 90.9) mm³, S1: 384.2 (SD, 145.0) mm³, and S2: 192.4 (SD, 52.6) mm³. Dorsal root ganglion volume increased from L4 to S1 and decreased from S1 to S2 (P < .001). Dorsal root ganglion volume correlated with subject height (r = . 22, P < .001) and was higher in men (P < .001). CONCLUSIONS: Dorsal root ganglion volumetry by measuring its principal geometric axes on MR gangliography can be substantially optimized. By means of this optimization, dorsal root ganglion volume distribution was estimated in a large healthy cohort for the clinically most relevant lumbosacral levels, L4-S2.

Spin echo formation in muscle tissue.

Determination of the spin echo signal evolution and of transverse relaxation rates is of high importance for microstructural modeling of muscle tissue in magnetic resonance imaging. So far, numerically exact solutions for the NMR signal dynamics in muscle tissue models have been reported only for the gradient echo free induction decay, with spin echo problems usually solved by approximate methods. In this work, we modeled the spin echo signal numerically exact by discretizing the radial dimension of the Bloch-Torrey equation and expanding the angular dependency in terms of even Chebyshev polynomials. This allows us to express the time dependence of the local magnetization as a closed-form matrix expression. Using this method, we were able to accurately capture the spin echo local and total magnetization dynamics. The obtained transverse relaxation rates showed a high concordance with random walker and finite-element simulations. We could demonstrate that in cases of smaller diffusion coefficients, the commonly used strong collision approximation significantly underestimates the true value considerably. Instead, the limiting behavior in this regime is correctly described either by the full solution or by the slow diffusion approximation. Experimentally measured transverse relaxation rates of a mouse limb muscle showed an angular dependence in accordance with the theoretical prediction.

Magnetic particle imaging for artifact-free imaging of intracranial flow diverter stents: A phantom study.

PURPOSE: Magnetic Particle Imaging (MPI) is a new, background- and radiation-free tomographic imaging method that enables near real-time imaging of superparamagnetic iron-oxide nanoparticles (SPIONs) with high temporal and spatial resolution. This phantom study aims to investigate the potential of MPI for visualization of the stent lumen in intracranial flow diverters (FD). METHODS: Nitinol FD of different dimensions (outer diameter: 3.5 mm, 4.0 mm, 5.5 mm; total length: 22-40 mm) were scanned in vascular phantoms in a custom-built MPI scanner (in-plane resolution: ~ 2 mm, field of view: 65 mm length, 29 mm diameter). Phantoms were filled with diluted (1:50) SPION tracer agent Ferucarbotran (10 µmol (Fe)/ml; NaCL). Each phantom was measured in 32 different projections (overall acquisition time per image: 3200 ms, 5averages). After image reconstruction from raw data, two radiologists assessed image quality using a 5-point Likert scale. The signal intensity profile was measured using a semi-automatic evaluation tool. RESULTS: MPI visualized the lumen of all FD without relevant differences between the stented vessel phantom and the reference phantom. At 3.5 mm image quality was slightly inferior to the larger diameters. The FD themselves neither generated an MPI signal nor did they lead to relevant imaging artifacts. Ratings of both radiologists showed no significant difference, interrater reliability was good (ICC 0.84). A quantitative evaluation of the signal intensity profile did not reveal any significant differences (p > 0.05) either. CONCLUSION: MPI visualizes the lumen of nitinol FD stents in vessel phantoms without relevant stent-induced artifacts.

Spin echoes: full numerical solution and breakdown of approximative solutions.

The spin echo signal from vessels in Krogh's capillary model as well in the random distribution vessel model are studied by numerically solving the Bloch-Torrey equation. A comparison is made with the Gaussian local phase approximation, the Gaussian phase approximation and the strong-collision approximation. Differences between the Gaussian local phase approximation and the Gaussian phase approximation are explained. In the intermediate diffusion regime, the full numerical solution shows oscillations which are absent in any of the approximate solutions. In the limit of large diffusion coefficients, where the approximations become exact, the signal shows a linear-exponential decay governed by a single parameter. The features of the exact numerical solution can be explained by an analytically solvable discrete two-level model. There is a one-to-one correspondence between the different diffusion regimes and the three cases of the damped harmonic oscillator.

Pseudo-diffusion effects in lung MRI.

Magnetic resonance imaging of lung tissue is strongly influenced by susceptibility effects between spin-bearing water molecules and air-filled alveoli. The measured lineshape, however, also depends on the interplay between susceptibility effects and blood-flow around alveoli that can be approximated as pseudo-diffusion. Both effects are quantitatively described by the Bloch-Torrey-equation, which was so far only solved for dephasing on the alveolar surface. In this work, we extend this model to the whole range of physiological relevant air volume fractions. The results agree very well with in vivo measurements in human lung tissue.

Spin dephasing around randomly distributed vessels.

We analyze the gradient echo signal in the presence of blood vessel networks. Both, diffusion and susceptibility effects are analytically emphasized within the Bloch-Torrey equation. Solving this equation, we present the first exact description of the local magnetization around a single vessel. This allows us to deduce the gradient echo signal of parallel vessels randomly distributed in a plane, which is valid for arbitrary mean vessel diameters in the range of physiological relevant blood volume fractions. Thus, the results are potentially relevant for gradient echo measurements of blood vessel networks with arbitrary vessel size.

Dependence of the frequency distribution around a vessel on the voxel orientation.

In this work the frequency distribution around a vessel inside a cubic voxel is investigated. Therefore, the frequency distribution is calculated in dependence on the orientation of the voxel according to the external magnetic field. The frequency distribution exhibits an interesting peak structure that cannot be explained by the established Krogh's vessel model. The results were validated with phantom measurements and in vivo measurements that agree very well with the developed theory.

Spin dephasing in the Gaussian local phase approximation.

The Brownian motion of spins diffusing in an inhomogeneous magnetic field created by susceptibility effects is considered. Applying the correct form of the Gaussian approximation, the method allows calculating the local magnetization as well as the free induction decay for all diffusion regimes. The phase accumulated during the diffusional motion is treated by an averaging over all possible trajectories in terms of the Gaussian local phase approximation. Predictions of the Gaussian local phase approximation are compared with the Gaussian phase approximation for diffusion in a constant gradient in a slab, a cylinder, and a sphere. The Gaussian local phase approximation, thereby, shows several advantages compared to the Gaussian phase approximation: it is also valid in the static dephasing regime, predicts correctly both transverse components of the magnetization, and yields information about the local magnetization.

Magnetic Particle Imaging for Quantification of Vascular Stenoses: A Phantom Study.

Magnetic particle imaging (MPI) is a promising new tomographic imaging method to detect the spatial distribution of superparamagnetic iron-oxide nanoparticles (SPIOs). The aim of this paper was to investigate the potential of MPI to quantify artificial stenoses in vessel phantoms. Custom-made stenosis phantoms (length 40 mm; inner diameter 8 mm) with different degrees of stenosis (0%, 25%, 50%, 75%, and 100%) were scanned in a custom-built MPI scanner (in-plane resolution: ~1-1.5 mm and field of view: 65 29 29 mm3). Phantoms were filled with diluted Feru-carbotran [SPIO agent, 5 mmol (Fe)/l]. Each measurement (overall acquisition time: 20 ms per image, 400 averages) was repeated ten times to assess reproducibility. The MPI signal was used for semi-automatic stenosis quantification. Two stenosis evaluation approaches were compared based on the signal intensity profile alongside the stenosis phantoms. Using a novel multi-step image evaluation approach, MPI allowed for accurate quantification of different stenosis grades. While low grade stenoses were slightly over-estimated, high grade stenoses were slightly underestimated. In particular, the 0%, 25%, and 50% stenosis phantoms revealed a 6.2% ± 0.8, 25.7% ± 1.0, and 48.0% ± 1.5 stenosis, respectively. The higher grade 75% stenosis phantom revealed a 73.3% ± 2.8 and the 100% stenosis phantom a 95.8%± 1.9 stenosis. MPI accurately visualized and quantified different stenosis grades in vessel phantoms with high reproducibility demonstrating its great potential for fast and radiation-free preclinical cardiovascular imaging.

The influence of spatial patterns of capillary networks on transverse relaxation.

Tissue-inherent relaxation parameters offer valuable information about the arrangement of capillaries: in an external field, capillaries act as magnetic perturbers to generate local inhomogeneous fields due to the susceptibility difference of deoxygenated blood and the surrounding tissue. These field inhomogeneities influence the free induction decay in a characteristic way, and, conversely, the above tissue parameters can be recovered by multi-parametric fits of adequate theoretical models to experimentally sampled free induction decays. In this work we study the influence of different spatial patterns of capillary positions on the free induction decay. Starting from the standard single capillary approximation (Krogh cylinder) for a symmetric array of capillaries, the free induction decay is analyzed for increasingly random capillary positions, using a previously described Gibbs point field model. The effects of diffusion are implemented with a flexible and fast random walk simulation. We find that the asymmetric form of the obtained frequency distribution is more robust against variations of capillary radii than against shifts of capillary positions, and further that, for an inclusion of diffusion effects, the single capillary approximation models the uniform alignment of capillaries in the hexagonal lattice to great accuracy. An increase in randomization of capillary positions then leads to a significant change in relaxation times. This effect, however, is found less pronounced than that of changes in the off-resonance field strengths which are controlled by the oxygen extraction fraction, thus indicating that observed changes in BOLD imaging are more likely to be attributed to changes in oxygenation than to capillary alignment.

Dephasing and diffusion on the alveolar surface.

We propose a surface model of spin dephasing in lung tissue that includes both susceptibility and diffusion effects to provide a closed-form solution of the Bloch-Torrey equation on the alveolar surface. The nonlocal susceptibility effects of the model are validated against numerical simulations of spin dephasing in a realistic lung tissue geometry acquired from synchotron-based µCT data sets of mouse lung tissue, and against simulations in the well-known Wigner-Seitz model geometry. The free induction decay is obtained in dependence on microscopic tissue parameters and agrees very well with in vivo lung measurements at 1.5 Tesla to allow a quantification of the local mean alveolar radius. Our results are therefore potentially relevant for the clinical diagnosis and therapy of pulmonary diseases.

Spin dephasing in a magnetic dipole field around large capillaries: Approximative and exact results.

We present an analytical solution of the Bloch-Torrey equation for local spin dephasing in the magnetic dipole field around a capillary and for ensembles of capillaries, and adapt this solution for the study of spin dephasing around large capillaries. In addition, we provide a rigorous mathematical derivation of the slow diffusion approximation for the spin-bearing particles that is used in this regime. We further show that, in analogy to the local magnetization, the transverse magnetization of one MR imaging voxel in the regime of static dephasing (where diffusion effects are not considered) is merely the first term of a series expansion that constitutes the signal in the slow diffusion approximation. Theoretical results are in agreement with experimental data for capillaries in rat muscle at 7T.

CPMG relaxation rate dispersion in dipole fields around capillaries.

Transverse relaxation rates for Carr-Purcell-Meiboom-Gill (CPMG) sequences increase with inter-echo time in presence of microscopic magnetic field inhomogeneities due to nuclear spin diffusion. For a weak field approximation that includes diffusion effects, the CPMG relaxation rate shift for proton diffusion around capillaries in muscle tissue can be expressed in terms of a frequency correlation function and the inter-echo time. The present work provides an analytical expression for the local relaxation rate shift that is dependent on local blood volume fraction, diffusion coefficient, capillary radius, susceptibility difference and inter-echo time. Asymptotic regions of the model are in agreement with previous modeling results of Brooks et al., Luz et al. and Ziener et al. In comparison with simulation data, the model shows an equal or better accuracy than established approximations. Also, model behavior coincides with experimental data for rat heart and skeletal muscle. The present work provides analytical tools to extract sub-voxel information about uniform capillary networks that can be used to study capillary organization or micro-circulatory remodeling.

Free induction decay caused by a dipole field.

We analyze the free induction decay of nuclear spins under the influence of restricted diffusion in a magnetic dipole field around cylindrical objects. In contrast to previous publications no restrictions or simplifications concerning the diffusion process are made. By directly solving the Bloch-Torrey equation, analytical expressions for the magnetization are given in terms of an eigenfunction expansion. The field strength-dependent complex nature of the eigenvalue spectrum significantly influences the shape of the free induction decay. As the dipole field is the lowest order of the multipole expansion, the obtained results are important for understanding fundamental mechanisms of spin dephasing in many other applied fields of nuclear magnetic resonance such as biophysics or material science. The analytical methods are applied to interpret the spin dephasing in the free induction decay in cardiac muscle and skeletal muscle. A simple expression for the relevant transverse relaxation time is found in terms of the underlying microscopic parameters of the muscle tissue. The analytical results are in agreement with experimental data. These findings are important for the correct interpretation of magnetic resonance images for clinical diagnosis at all magnetic field strengths and therapy of cardiovascular diseases.

Spin dephasing in a magnetic dipole field.

Transverse relaxation by dephasing in an inhomogeneous field is a general mechanism in physics, for example, in semiconductor physics, muon spectroscopy, or nuclear magnetic resonance. In magnetic resonance imaging the transverse relaxation provides information on the properties of several biological tissues. Since the dipole field is the most important part of the multipole expansion of the local inhomogeneous field, dephasing in a dipole field is highly important in relaxation theory. However, there have been no analytical solutions which describe the dephasing in a magnetic dipole field. In this work we give a complete analytical solution for the dephasing in a magnetic dipole field which is valid over the whole dynamic range.

Fast CPMG-based Bloch-Siegert B(1)+ mapping.

A novel method for B(1)+ mapping based on the Bloch-Siegert (BS) shift was recently presented. This method applies off-resonant pulses before signal acquisition to encode B(1) information into the signal phase. BS-based methods possess significant advantages in measurement time and accuracy compared to magnitude-based B(1)+ methods. This study extends the idea of BS B(1)+ mapping to Carr, Purcell, Meiboom, Gill (CPMG)-based multi-spin-echo (BS-CPMG-MSE) and turbo-spin-echo (BS-CPMG-TSE) imaging. Compared to BS-based spin echo imaging (BS-SE), faster acquisition of the B(1)+ information was possible using the BS-CPMG-TSE sequence. Furthermore, signal loss by T(2)* effects could be minimized using these spin echo-based techniques. These effects are critical for gradient echo-based BS methods at high field strengths. However, multi-spin-echo-based BS B(1) methods inherently possess high specific absorption rates. Thus, the relative specific absorption rate of BS-CPMG-TSE sequences was estimated and compared with the specific absorption rate produced by BS-SE sequences.

Improved encoding strategy for CPMG-based Bloch-Siegert B(1)(+) mapping.

Bloch-Siegert (BS) based B(1)(+) mapping methods use off-resonant pulses to encode quantitative B(1)(+) information into the signal phase. It was recently shown that the principle behind BS-based B(1)(+) mapping can be expanded from spin echo (BS-SE) and gradient-echo (BS-FLASH) based BS B(1)(+) mapping to methods such as Carr, Purcell, Meiboom, Gill (CPMG)-based turbo-spin echo (BS-CPMG-TSE) and multi-spin echo (BS-CPMG-MSE) imaging. If CPMG conditions are preserved, BS-CPMG-TSE allows fast acquisition of the B(1)(+) information and BS-CPMG-MSE enables simultaneous mapping of B(1)(+), M(0), and T(2). To date, however, two separate MRI experiments must be performed to enable the calculation of B(1)(+) maps. This study investigated a modified encoding strategy for CPMG BS-based methods to overcome this limitation. By applying a "bipolar" off-resonant BS pulse before the refocusing pulse train, the needed phase information was able to be encoded into different echo images of one echo train. Thus, this technique allowed simultaneous B(1)(+) and T(2) mapping in a single BS-CPMG-MSE experiment. To allow single-shot B(1)(+) mapping, this method was also applied to turbo-spin echo imaging. Furthermore, the presented modification intrinsically minimizes phase-based image artifacts in BS-CPMG-TSE experiments.

Application of compressed sensing to in vivo 3D ¹9F CSI.

This study shows how applying compressed sensing (CS) to (19)F chemical shift imaging (CSI) makes highly accurate and reproducible reconstructions from undersampled datasets possible. The missing background signal in (19)F CSI provides the required sparsity needed for application of CS. Simulations were performed to test the influence of different CS-related parameters on reconstruction quality. To test the proposed method on a realistic signal distribution, the simulation results were validated by ex vivo experiments. Additionally, undersampled in vivo 3D CSI mouse datasets were successfully reconstructed using CS. The study results suggest that CS can be used to accurately and reproducibly reconstruct undersampled (19)F spectroscopic datasets. Thus, the scanning time of in vivo(19)F CSI experiments can be significantly reduced while preserving the ability to distinguish between different (19)F markers. The gain in scan time provides high flexibility in adjusting measurement parameters. These features make this technique a useful tool for multiple biological and medical applications.

Diffusion effects on the CPMG relaxation rate in a dipolar field.

The diffusion in the magnetic dipolar field around a sphere is considered. The diffusion is restricted to the space between two concentric spheres, where the inner sphere is the source of the magnetic dipolar field. Analytical expressions for the CPMG transverse relaxation rate as well as the free induction decay and the spin echo time evolution are given in the Gaussian approximation. The influence of the inter-echo time is analyzed. The limiting cases of small and large inter-echo times as well as the short and long time behavior are evaluated.