in-vivo-imaging-optic-nerve-fiber-integrity-contrast-enhanced-mri

<em>In vivo</em> Imaging of Optic Nerve Fiber Integrity by Contrast-Enhanced MRI in Mice

The rodent visual system encompasses retinal ganglion cells and their axons that form the optic nerve to enter thalamic and midbrain centers, and ...

Jena University Hospital

The aim of this study was to develop and implement an algorithm for the co-registration of 3D breast MRI sets acquired at two slightly different patient positions (repetitive examination). Combined translation and rotation with locally varying parameters were applied for the purpose of coordinate transformation. A phantom allowing selective changes of the volume of the glandular tissue model was developed, in order to prove the robustness of the proposed matcher against local changes. Serial 3D data sets of phantoms and volunteers were acquired to validate the routines. Co-registration was performed using mutual information (MI) as a similarity measure of the matching of the acquired images. In the phantom study, the phantom was deliberately shifted and rotated around horizontal and vertical axes. Starting the registration with global translations using a rigid matcher, the horizontal (phi) and vertical (theta) rotation angles were optimized in an iteration loop for each slice. This method was then applied to the breast data sets. Application of the algorithm on serial 3D MR data sets improved the co-registration especially in consideration of varying local tissue volumes. The algorithm represents a compromise between a pure rigid and an elastic 3D matcher.

[Validation of an entropy-based algorithm for registration of serial 3D MR mammography data].

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.

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

An increasing number of animal experiments are currently conducted on clinical MR systems. Motion artefacts due to breathing can become quite apparent, in particular with abdominal examinations. These artefacts can be reduced by using a triggered acquisition. However, the built-in detectors in human whole-body scanners are usually not sensitive enough to detect the tiny movements of small rodents. Therefore, a sensitive optical motion detector was developed together with a simple, robust analogue circuit. This circuit converts the original optical signal into an electrical one, compensates slow drifts and offsets, and finally generates a transistor-transistor logic trigger signal as input for the clinical whole-body magnetic resonance scanner. The trigger was successfully applied in mouse experiments.

A robust optical respiratory trigger for small rodents in clinical whole-body MR systems.

Echo planar imaging (EPI) in combination with PROPELLER allows high-resolution diffusion-weighted imaging. In this study, the image quality of short-axis and long-axis PROPELLER was compared and optimized using phantom and in vivo data. Furthermore, diffusion-weighted measurements using both sequences were compared with those of a reference sequence. It was found that the long-axis sequence provided better image quality, whereas the results of the diffusion weighted measurements were more accurate with the short-axis variant. and that the results of the diffusion weighted measurements of both sequences agreed well with those of the reference sequence.

[Comparison of long-axis and short-axis PROPELLER-EPI for diffusion-weighted Magnetic Resonance Imaging].

A magnetic resonance imaging (MRI) technique for diffusion weighted imaging (DWI) is described which, in contrast to echo planar imaging (EPI), is insensitive to off-resonance effects caused by tissue susceptibility differences, magnetic field inhomogeneities, or chemical shifts. The sequence combines a diffusion weighted (DW) spin-echo preparation and a stimulated echo acquisition mode (STEAM) module. Inner volume imaging (IVI) allows reduced rectangular field-of-view (FoV) in the phase encode direction, while suppressing aliasing artifacts that are usually the consequence of reduced FoVs. Sagittal turbo-STEAM images of the lumbar spine were acquired at 3.0T with 2.0 × 2.0 mm² in-plane resolution and 7 mm slice thickness with acquisition times of 407 ms per image. To calculate the apparent diffusion coefficient (ADC) in lumbar intervertebral disks (IVDs), the DW gradients were applied in three orthogonal gradient directions with b-values of 0 and 300 s/mm². For initial assessment of the ADC of normal and abnormal IVDs a pilot study with 8 subjects was performed. Mean ADC values of all normal IVDs were (2.27±0.40)×10⁻³ mm²/s and (1.89±0.34)×10⁻³ mm²/s for turbo-STEAM IVI and SE-EPI acquisition, respectively. Corresponding mean ADC values, averaged over all abnormal disks, were (1.93±0.39)×10⁻³ mm²/s and (1.51±0.46)×10⁻³ mm²/s, respectively, indicating a substantial ADC decrease (p<0.001).

Diffusion weighted inner volume imaging of lumbar disks based on turbo-STEAM 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).

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

Magnetic resonance imaging olfactory bulb (OB) volumetry (OBV) is already used as a complementary prognostic tool to assess olfactory disorders. However, a reference standard in imaging for OBV has not been established. The aim of this in vitro study was to compare volumetric results of different magnetic resonance sequences for OBV at 3 T to genuine OB volumes measured by water displacement.

In vitro comparison of water displacement method and 3 Tesla MRI for MR-volumetry of the olfactory bulb: which sequence is appropriate?

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.

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

To investigate the potential of a clinical 3 T scanner to perform MRI of small rodents.

Possibilities and limitations for high resolution small animal MRI on a clinical whole-body 3T scanner.

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.

Deformation-based brain morphometry in rats.

Performing magnetic resonance imaging (MRI) experiments with small animals requires continuous monitoring of vital parameters, especially the respiration rate. Clinical whole-body MR scanners represent an attractive option for preclinical imaging as dedicated animal scanners are cost-intensive in both investment and maintenance, thus limiting their availability. Even though impressive image quality is achievable with clinical MR systems in combination with special coils, their built-in physiologic monitoring and triggering units are often not suited for small animal imaging. In this work, we present a simple, MRI compatible low cost solution to monitor the respiration and heart rate of small animals in a clinical whole-body MR scanner. The recording and processing of the biosignals as well as the optimisation of the respiratory trigger generation is decribed. Additionally rat and mouse in-vivo MRI experiments are presented to illustrate the effectiveness of the monitoring and respiratory trigger system in suppressing motion artifacts.

MRI compatible small animal monitoring and trigger system for whole body scanners.

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.

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

Dysfunctional NF-κB and brain myelin formation.

NF-κB 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-κB. 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-κB 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.

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

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

Article	Year
[Validation of an entropy-based algorithm for registration of serial 3D MR mammography data]. Zeitschrift für medizinische Physik\| PubMed ID: 16008080	2005
Improved elimination of phase effects from background field inhomogeneities for susceptibility weighted imaging at high magnetic field strengths. Magnetic resonance imaging\| PubMed ID: 18524525	2008
A robust optical respiratory trigger for small rodents in clinical whole-body MR systems. Biomedizinische Technik. Biomedical engineering\| PubMed ID: 18601622	2008
[Comparison of long-axis and short-axis PROPELLER-EPI for diffusion-weighted Magnetic Resonance Imaging]. Zeitschrift für medizinische Physik\| PubMed ID: 20888743	2011
Diffusion weighted inner volume imaging of lumbar disks based on turbo-STEAM acquisition. Zeitschrift für medizinische Physik\| PubMed ID: 21239149	2011
Resolving arterial phase and temporal enhancement characteristics in DCE MRM at high spatial resolution with TWIST acquisition. Journal of magnetic resonance imaging : JMRI\| PubMed ID: 21769981	2011
In vitro comparison of water displacement method and 3 Tesla MRI for MR-volumetry of the olfactory bulb: which sequence is appropriate? Academic radiology\| PubMed ID: 21782479	2011
Magnetic resonance imaging of the mouse visual pathway for in vivo studies of degeneration and regeneration in the CNS. NeuroImage\| PubMed ID: 21835252	2012
Possibilities and limitations for high resolution small animal MRI on a clinical whole-body 3T scanner. Magma (New York, N.Y.)\| PubMed ID: 22042538	2012
Deformation-based brain morphometry in rats. NeuroImage\| PubMed ID: 22776449	2012
MRI compatible small animal monitoring and trigger system for whole body scanners. Zeitschrift für medizinische Physik\| PubMed ID: 23962379	2014
Fast low-angle shot diffusion tensor imaging with stimulated echo encoding in the muscle of rabbit shank. NMR in biomedicine\| PubMed ID: 24151092	2014
Dysfunctional NF-κB and brain myelin formation. European journal of human genetics : EJHG\| PubMed ID: 24169526	2014
NF-κB controls axonal regeneration and degeneration through cell-specific balance of RelA and p50 in the adult CNS. Journal of cell science\| PubMed ID: 24860143	2014
Retrospective reconstruction of cardiac cine images from golden-ratio radial MRI using one-dimensional navigators. Journal of magnetic resonance imaging : JMRI\| PubMed ID: 24895008	2013

Karl-Heinz Herrmann

Biography

JoVE Journal Publications

Other Publications