Karl-Heinz Herrmann

3D printing of MRI compatible components: why every MRI research group should have a low-budget 3D printer.

PURPOSE To evaluate low budget 3D printing technology to create MRI compatible components. MATERIAL AND METHODS A 3D printer is used to create customized MRI compatible components, a loop-coil platform and a multipart mouse fixation. The mouse fixation is custom fit for a dedicated coil and facilitates head fixation with bite bar, anesthetic gas supply and biomonitoring sensors. The mouse fixation was tested in a clinical 3T scanner. RESULTS All parts were successfully printed and proved MR compatible. Both design and printing were accomplished within a few days and the final print results were functional with well defined details and accurate dimensions (Δ<0.4mm). MR images of the mouse head clearly showed reduced motion artifacts, ghosting and signal loss when using the fixation. CONCLUSIONS We have demonstrated that a low budget 3D printer can be used to quickly progress from a concept to a functional device at very low production cost. While 3D printing technology does impose some restrictions on model geometry, additive printing technology can create objects with complex internal structures that can otherwise not be created by using lathe technology. Thus, we consider a 3D printer a valuable asset for MRI research groups.

Improved elimination of phase effects from background field inhomogeneities for susceptibility weighted imaging at high magnetic field strengths

To enhance susceptibility-related contrast of magnetic resonance images, the phase of susceptibility weighted data needs to be corrected for background inhomogeneities and phase wraps caused by them. Current methods either use homodyne filtering or a combination of phase unwrapping and high pass filtering. The drawback of homodyne filtering is incomplete elimination of phase wraps in areas with steep phase topography produced by background inhomogeneities of the static magnetic field. The disadvantage of phase unwrapping is that it requires subsequent high pass filtering, which introduces artifacts in areas with very steep transitions, such as areas near interfaces between parenchyma and bone or air. A method is proposed that reduces the artifacts associated with high pass filtering without sacrificing the advantages of phase unwrapping. This technique is demonstrated with phantom data at 1.5 T and with human data at 1.5, 3 and 7 T.

Resolving arterial phase and temporal enhancement characteristics in DCE MRM at high spatial resolution with TWIST acquisition

To investigate the potential of a view‐sharing 3D fast gradient‐echo sequence using pseudo random trajectories (TWIST) to achieve very short acquisition times with high in‐plane resolution and good volume coverage and its application to dynamic contrast‐enhanced (DCE) breast magnetic resonance imaging (MRI).

Neuroimaging Evidence of a Bilateral Representation for Visually Presented Numbers

The clustered architecture of the brain for different visual stimulus categories is one of the most fascinating topics in the cognitive neurosciences. Interestingly, recent research suggests the existence of additional regions for newly acquired stimuli such as letters (letter form area; LFA; Thesen et al., 2012) and numbers (visual number form area; NFA; Shum et al., 2013). However, neuroimaging methods thus far have failed to visualize the NFA in healthy participants, likely due to fMRI signal dropout caused by the air/bone interface of the petrous bone (Shum et al., 2013). In the current study, we combined a 64-channel head coil with high spatial resolution, localized shimming, and liberal smoothing, thereby decreasing the signal dropout and increasing the temporal signal-to-noise ratio in the neighborhood of the NFA. We presented subjects with numbers, letters, false numbers, false letters, objects and their Fourier randomized versions. A group analysis showed significant activations in the inferior temporal gyrus at the previously proposed location of the NFA. Crucially, we found the NFA to be present in both hemispheres. Further, we could identify the NFA on the single-subject level in most of our participants. A detailed analysis of the response profile of the NFA in two separate experiments confirmed the whole-brain results since responses to numbers were significantly higher than to any other presented stimulus in both hemispheres. Our results show for the first time the existence and stimulus selectivity of the NFA in the healthy human brain. SIGNIFICANCE STATEMENT This fMRI study shows for the first time a cluster of neurons selective for visually presented numbers in healthy human adults. This visual number form area (NFA) was found in both hemispheres. Crucially, numbers have gained importance for humans too recently for neuronal specialization to be established by evolution. Therefore, investigations of this region will greatly advance our understanding of learning and plasticity in the brain. In addition, these results will aid our knowledge regarding related neurological illnesses (e.g., dyscalculia). To overcome the fMRI signal dropout in the neighborhood of the NFA, we combined high spatial resolution with liberal smoothing. We believe that this approach will be useful to the broad neuroimaging community.

Magnetic resonance imaging of the mouse visual pathway for in vivo studies of degeneration and regeneration in the CNS.

Traditionally, depiction of isolated CNS fiber tracts is achieved by histological post mortem studies. As a tracer-dependent strategy, the calcium analog manganese has proved valuable for in vivo imaging of CNS trajectories, particularly in rats. However, adequate protocols in mice are still rare. To take advantage of the numerous genetic mouse mutants that are available to study axonal de- and regeneration processes, a MnCl2-based protocol for high-resolution contrast-enhanced MRI (MEMRI) of the visual pathway in mice acquired on a widely used clinical 3 Tesla scanner was established. Intravitreal application of MnCl2 significantly enhanced T1-weighted contrast and signal intensity along the retino-petal projection enabling its reconstruction in a 3D mode from a maximum intensity projection (MIP) calculated dataset. In response to crush injury of the optic nerve, axonal transport of MnCl2 was diminished and completely blocked proximal and distal to the lesion site, respectively. Conditions of Wallerian degeneration after acute optic nerve injury accelerated Mn2+-enhanced signal fading in axotomized projection areas between 12 and 24 h post-injury. In long-term regeneration studies 12 months after optic nerve injury, the MRI protocol proved highly sensitive and discriminated animals with rare spontaneous axonal regrowth from non-regenerating specimens. Also, structural MRI aspects shared high correlation with histological results in identical animals. Moreover, in a model of chronic neurodegeneration in p50/NF-κB-deficient mice, MnCl2-based neuron-axonal tracing supported by heat map imaging indicated neuropathy of the visual pathway due to atrophy of optic nerve fiber projections. Toxic effects of MnCl2 at MRI contrast-relevant dosages in repetitive administration protocols were ruled out by histological and optometric examinations. At higher dosages, photoreceptors, not retinal ganglion cells, turned out as most susceptible to the well-known toxicity of MnCl2. Our data accentuate in vivo MEMRI of the murine visual system as a highly specific and sensitive strategy to uncover axonal degeneration and restoration processes, even in a functional latent state. We expect MEMRI to be promising for future applications in longitudinal studies on development, aging, or regeneration of CNS projections in mouse models mimicking human CNS pathologies.

Fast low-angle shot diffusion tensor imaging with stimulated echo encoding in the muscle of rabbit shank.

In the past, spin‐echo (SE) echo planar imaging(EPI)‐based diffusion tensor imaging (DTI) has been widely used to study the fiber structure of skeletal muscles in vivo. However, this sequence has several shortcomings when measuring restricted diffusion in small animals, such as its sensitivity to susceptibility‐related distortions and a relatively short applicable diffusion time. To address these limitations, in the current work, a stimulated echo acquisition mode (STEAM) MRI technique, in combination with fast low‐angle shot (FLASH) readout (turbo‐STEAM MRI), was implemented and adjusted for DTI in skeletal muscles. Signal preparation using stimulated echoes enables longer effective diffusion times, and thus the detection of restricted diffusion within muscular tissue with intracellular distances up to 100 µm. Furthermore, it has a reduced penalty for fast T2 muscle signal decay, but at the expense of 50% signal loss compared with a SE preparation. Turbo‐STEAM MRI facilitates high‐resolution DTI of skeletal muscle without introducing susceptibility‐related distortions. To demonstrate its applicability, we carried out rabbit in vivo measurements on a human whole‐body 3 T scanner. DTI parameters of the shank muscles were extracted, including the apparent diffusion coefficient, fractional anisotropy, eigenvalues and eigenvectors. Eigenvectors were used to calculate maps of structural parameters, such as the planar index and the polar coordinates θ and ϕ of the largest eigenvector. These parameters were compared between three muscles. θ and ϕ showed clear differences between the three muscles, reflecting different pennation angles of the underlying fiber structures. Fiber tractography was performed to visualize and analyze the architecture of skeletal pennate muscles. Optimization of tracking parameters and utilization of T2‐weighted images for improved muscle boundary detection enabled the determination of additional parameters, such as the mean fiber length. The presented results support the applicability of turbo‐STEAM MRI as a promising method for quantitative DTI analysis and fiber tractography in skeletal muscles. Copyright

Deformation-based brain morphometry in rats

Magnetic resonance imaging (MRI)-based morphometry provides in vivo evidence for macro-structural plasticity of the brain. Experiments on small animals using automated morphometric methods usually require expensive measurements with ultra-high field dedicated animal MRI systems. Here, we developed a novel deformation-based morphometry (DBM) tool for automated analyses of rat brain images measured on a 3-Tesla clinical whole body scanner with appropriate coils. A landmark-based transformation of our customized reference brain into the coordinates of the widely used rat brain atlas from Paxinos and Watson (Paxinos Atlas) guarantees the comparability of results to other studies. For cross-sectional data, we warped images onto the reference brain using the low-dimensional nonlinear registration implemented in the MATLAB software package SPM8. For the analysis of longitudinal data sets, we chose high-dimensional registrations of all images of one data set to the first baseline image which facilitate the identification of more subtle structural changes. Because all deformations were finally used to transform the data into the space of the Paxinos Atlas, Jacobian determinants could be used to estimate absolute local volumes of predefined regions-of-interest. Pilot experiments were performed to analyze brain structural changes due to aging or photothrombotically-induced cortical stroke. The results support the utility of DBM based on commonly available clinical whole-body scanners for highly sensitive morphometric studies on rats.

NF-κB controls axonal regeneration and degeneration through cell-specific balance of RelA and p50 in the adult CNS.

ABSTRACT NF-&kgr;B is dually involved in neurogenesis and brain pathology. Here, we addressed its role in adult axoneogenesis by generating mutations of RelA (p65) and p50 (also known as NFKB1) heterodimers of canonical NF-&kgr;B. In addition to RelA activation in astrocytes, optic nerve axonotmesis caused a hitherto unrecognized induction of RelA in growth-inhibitory oligodendrocytes. Intraretinally, RelA was induced in severed retinal ganglion cells and was also expressed in bystander Müller glia. Cell-type-specific deletion of transactivating RelA in neurons and/or macroglia stimulated axonal regeneration in a distinct and synergistic pattern. By contrast, deletion of the p50 suppressor subunit promoted spontaneous and post-injury Wallerian degeneration. Growth effects mediated by RelA deletion paralleled a downregulation of growth-inhibitory Cdh1 (officially known as FZR1) and upregulation of the endogenous Cdh1 suppressor EMI1 (officially known as FBXO5). Pro-degenerative loss of p50, however, stabilized retinal Cdh1. In vitro, RelA deletion elicited opposing pro-regenerative shifts in active nuclear and inactive cytoplasmic moieties of Cdh1 and Id2. The involvement of NF-&kgr;B and cell-cycle regulators such as Cdh1 in regenerative processes of non-replicative neurons suggests novel mechanisms by which molecular reprogramming might be executed to stimulate adult axoneogenesis and treat central nervous system (CNS) axonopathies.

Retrospective reconstruction of cardiac cine images from golden-ratio radial MRI using one-dimensional navigators

To demonstrate radial golden‐ratio–based cardiac cine imaging by using interspersed one‐dimensional (1D) navigators.

Self-gated cardiac Cine MRI of the rat on a clinical 3 T MRI system.

The ability to perform small animal functional cardiac imaging on clinical MRI scanners may be of particular value in cases in which the availability of a dedicated high field animal MRI scanner is limited. Here, we propose radial MR cardiac imaging in the rat on a whole‐body clinical 3 T scanner in combination with interspersed projection navigators for self‐gating without any additional external triggering requirements for electrocardiogram (ECG) and respiration. Single navigator readouts were interspersed using the same TR and a high navigator frequency of 54 Hz into a radial golden‐angle acquisition. The extracted navigator function was thresholded to exclude data for reconstruction from inhalation phases during the breathing cycle, enabling free breathing acquisition. To minimize flow artifacts in the dynamic cine images a center‐out half echo radial acquisition scheme with ramp sampling was used. Navigator functions were derived from the corresponding projection navigator data from which both respiration and cardiac cycles were extracted. Self‐gated cine acquisition resulted in high‐quality cardiac images which were free of major artifacts with spatial resolution of up to 0.21 × 0.21 × 1.00 mm3 and a contrast‐to‐noise ratio (CNR) of 21 ± 3 between the myocardium and left ventricle. Self‐gated golden ratio based radial acquisition successfully acquired cine images of the rat heart on a clinical MRI system without the need for dedicated animal ECG equipment. Copyright