S. Haber-Pohlmeier,* C. Tötzke, E. Lehmann, N. Kardjilov, A. Pohlmeier, and S.E. Oswald
In situ investigations of the rhizosphere require high-resolution imaging tech- niques, which allow a look into the optically opaque soil compartment. We present the novel combination of magneticresonanceimaging (MRI) and neu- tron computed tomography (NCT) to achieve synergistic information such as water mobility in terms of three-dimensional (3D) relaxation time maps and total water content maps. Besides a stationary MRI scanner for relaxation time map- ping, we used a transportable MRI system on site in the NCT facility to capture rhizosphere properties before desiccation and after subsequent rewetting. First, we addressed two questions using water-filled test capillaries between 0.1 and 5 mm: which root diameters can still be detected by both methods, and to what extent are defined interfaces blurred by these imaging techniques? Going to real root system architecture, we demonstrated the sensitivity of the transportable MRI device by co-registration with NCT and additional validation using X-ray computed tomography. Under saturated conditions, we observed for the rhizo- sphere in situ a zone with shorter T1 relaxation time across a distance of about 1 mm that was not caused by reduced water content, as proven by successive NCT measurements. We conclude that the effective pore size in the pore network had changed, induced by a gel phase. After rewetting, NCT images showed a dry zone persisting while the MRI intensity inside the root increased considerably, indicat- ing water uptake from the surrounding bulk soil through the still hydrophobic rhizosphere. Overall, combining NCT and MRI allows a more detailed analysis of the rhizosphere’s functioning.
The present classification of cPFM is based on morpho- logic criteria (position of torcula, associated brain mal- formations) and quantitative evaluation (vermian area, transcerebellar diameter, brainstem–vermis (BV) angle). cPFM are usually identified by prenatal ultrasound screen- ing, however, a definitive diagnosis of a malformation may be difficult. Owing to the absence of acoustic shadowing, fetal magneticresonanceimaging (MRI) allows consis- tent and dedicated assessment of the cerebellum and even its small structures, such as the vermian lobules 11 . The
Hippocampal formation volumes represent a surrogate of neuronal plasticity and can be measured in MDD patients in vivo with structural magneticresonanceimaging (MRI) and automatic or manual volume analysis. Several previous studies reported hippocampal formation volume increases after treatment. After 8 weeks of antidepressant treatment with citalopram, hippocampal formation volume increases were demonstrated in patients with MDD ( Arnone et al., 2013 ). An earlier study reported volume increases after 12 weeks of treatment with paroxetine in patients with posttraumatic stress disorder ( Vermetten et al., 2003 ). A third study with a naturalistic inpatient setting and a mixed antidepressant treat- ment regime detailed posterior hippocampal volume increases after approximately 23 weeks of treatment ( Schermuly et al., 2011 ). Those studies highlight that pro-neuroplastic effects of monoaminergic antidepressants supported by animal litera- ture ( Pittenger and Duman, 2008 ; Malykhin and Coupland, 2015 ; Duman et al., 2016 ) could mediate hippocampal volume in- creases in humans. In contrast, several results found no volume increases after treatment ( Frodl et al., 2004 ; Vythilingam et al., 2004 ; Phillips et al., 2015 ). Still, subgroup analyses in 2 of these studies found hippocampal volume increases in remitted and acute patients continuously taking antidepressants ( Frodl et al., 2004 ; Phillips et al., 2015 ). While the reasons for discrepancies between these results remain unclear, further studies using re- fined methods are warranted.
of animals required. Depicting hippocampal volume using magneticresonanceimaging (MRI) is a frequently used method in this context. A Medline search in February 2011 using the Medical subject heading (MeSH) search terms “hippocampus” combined with “MRI” and “shape” or “volume” extracted 1864 publications. Modern imaging techniques in humans enable reliable measurement of hippocampal volume using native MRI contrast by defining hippocampal boarders using gray and white matter contrast differences (Konrad et al., 2009). Over the last decade high resolution 3D-images of mice, providing good structural insight, have been made possible by the development of adequate data acquisition protocols for small animal MRI (Natt et al., 2002). Despite these technical advances, few studies use native contrast for hippocampal volume delineation, which define hippocampal boarders manually (Maheswaran et al., 2009; Radyushkin et al., 2010). Low grey-white matter contrast in native MR images of mice makes it difficult to differentiate regional boarders. To enhance image contrast, brains are fixed and scanned using high field scanners and long MRI scans, a method called magneticresonance microscopy (MRM) (Badea et al., 2007). However this method does not utilize the great advantage of MRI, namely the possibility to repeatedly assess brain morphology in vivo. To overcome low regional intensity differences in vivo, contrast agents can be applied (Mendonça-Dias et al., 1983). The manganese ion Mn 2+ turns out to exhibit very promising
nation, but the distribution of the catalyst system on the monolith is challenging to reveal. For surface-sensitive analytic techniques, such as scanning electron microscopy (SEM) or transmission elec- tron microscopy (TEM), the monoliths need to be divided into small samples, which might inuence the catalyst system. To this end, less invasive techniques are therefore preferred. X-ray absorption techniques, such as computed tomography (CT), are sensitive to heavy elements and therefore lack in contrast between IL in the pores and the solid SiC matrix. For high resolution, micro- tomography (micro-CT) is favorable but also requires invasive cutting of the monolith. An alternative, non-invasive technique with lower resolution focusing on the liquid catalyst system is magneticresonanceimaging (MRI) being one of the modes of nuclear magneticresonance (NMR). MRI applies radiofrequency radiation and provides therefore access to optically opaque materials while unique contrast parameters such as NMR relaxation, can be exploited to increase the information content. Accordingly, MRI has been used for the examination of a wide range of both, so and hard materials such as polymers, food, plants and wood 18–22 as well
6 Center of Integrated Oncology (CIO), Universities of Cologne and Bonn, 50937 Cologne, Germany * Correspondence: email@example.com; Tel.: +49-2461-61-96357
Received: 4 January 2019; Accepted: 25 January 2019; Published: 29 January 2019 Abstract: Imaging techniques such as positron emission tomography (PET) and magneticresonanceimaging (MRI) provide valuable information about brain tumor patients. Particularly amino acid PET, advanced MRI techniques, and combinations thereof are of great interest for the non-invasive assessment of biological characteristics in patients with primary or secondary brain cancer. A methodological innovation that potentially advances research in patients with brain tumors is the increasing availability of hybrid PET/MRI systems, which enables the simultaneous acquisition of both imaging modalities. Furthermore, the advent of ultra-high field MRI scanners operating at magnetic field strengths of 7 T or more will allow further development of metabolic MR imaging at higher resolution. This review focuses on the combination of amino acid PET with MR spectroscopic imaging, perfusion- and diffusion-weighted imaging, as well as chemical exchange saturation transfer in patients with high-grade gliomas, especially glioblastomas.
MRI (magneticresonanceimaging) is an indispensable tool in the diagnosis of centrals nervous system (CNS) disorders such as spinal cord injury and multiple sclerosis (MS). In contrast, diagnosis of peripheral nerve injuries largely depends on clinical and electrophysiological parameters. Thus, currently MRI is not regularly used which in part is due to small nerve calibers and isointensity with surrounding tissue such as muscles. In this study we performed translational MRI research in mice to establish a novel MRI protocol visualizing intact and injured peripheral nerves in a non-invasive manner without contrast agents. With this protocol we were able to image even very small nerves and nerve branches such as the mouse facial nerve (diameter 100–300 µm) at highest spatial resolution. Analysis was performed in the same animal in a longitudinal study spanning 3 weeks after injury. Nerve injury caused hyperintense signal in T 2 -weighted images and an increase in nerve size of the proximal and distal nerve stumps were observed. Further hyperintense signal was observed in a bulb-like structure in the lesion site, which correlated histologically with the production of fibrotic tissue and immune cell infiltration. The longitudinal MR representation of the facial nerve lesions correlated well with physiological recovery of nerve function by quantifying whisker movement. In summary, we provide a novel protocol in rodents allowing for non-invasive, non-contrast agent enhanced, high-resolution MR imaging of small peripheral nerves longitudinally over several weeks. This protocol might further help to establish MRI as an important diagnostic and post-surgery follow-up tool to monitor peripheral nerve injuries in humans.
Abstract: The aim of this study was to assess trabecular bone morphology via magnetic-resonanceimaging (MRI) using microcomputed tomography (µCT) as the control group. Porcine bone samples were scanned with T1-weighted turbo spin echo sequence imaging, using TR 25 ms, TE 3.5 ms, FOV 100 × 100 × 90, voxel size 0.22 × 0.22 × 0.50 mm, and scan time of 11:18. µCT was used as the control group with 80 kV, 125 mA, and a voxel size of 16 µm. The trabecular bone was segmented on the basis of a reference threshold value and morphological parameters. Bone volume (BV), Bone-volume fraction (BvTv), Bone specific surface (BsBv), trabecular thickness (TbTh), and trabecular separation (TbSp) were evaluated. Paired t-test and Pearson correlation test were performed at p = 0.05. MRI overestimated BV, BvTv, TbTh, and TbSp values. BsBv was the only parameter that was underestimated by MRI. High statistical correlation (r = 0.826; p < 0.05) was found for BV measurements. Within the limitations of this study, MRI overestimated trabecular bone parameters, but with a statistically significant fixed linear offset.
Atomic nuclei of non-zero spin configuration also carry magnetic moments. However, these moments are negligibly small in comparison to those of electrons. Sensitive techniques, such as magneticresonanceimaging (MRI), are able to detect such faint nuclear moments via excitation under resonance conditions. MRI represents a noninvasive imaging routine for the detailed visualization of body structures, and is particularly suitable for the high-contrast depiction of soft tissues. Selective focusing during the recording procedure enables the production of sectional images of the area of interest. The individual pictures are finally put together to yield three-dimensional models of the investigated zone. A further benefit is that MRI involves no ionizing radiation. The scientists and later Nobel Prize winners Paul C. Lauterbur and Sir Peter Mansfield extended the ideas of nuclear magneticresonance for imaging purposes, and were leading in the development of MRI. The central role in clinical MRI is played by hydrogen nuclei which consist of a single proton and appear ubiquitously in the human body.
Abdominal ultrasound (US) is an almost ubiquitously available and noninvasive method for investigation of abdominal organs like the pan- creas. Therefore, it is often used as the first imaging method even when the patient has to undergo further imaging examinations. However, US is a highly operator-dependent technique, and imaging quality can be lim- ited for example due to intestinal gas or marked obesity (Brown, Sirlin, Hoyt, & Casola, 2003). Other noninvasive imaging techniques for evalua- tion of the pancreas include computed tomography (CT) and magneticresonanceimaging (MRI). They produce cross-sectional images usually in transversal orientation. Although operator effects have been demon- strated for these techniques as well, they are less pronounced than in US, so that MRI measurements are often considered to be more reliable (Ryan, Semelka, Molina, Yonkers, & Vaidean, 2010; van Vliet et al., 2008). Compared to CT, MRI provides better soft tissue contrast and in combi- nation with magneticresonance cholangiopancreatography (MRCP) it can be used for evaluating of the pancreatic duct (Bulow et al., 2014; Mensel et al., 2014). Validity of different imaging modalities has been assessed for cystic (Lee et al., 2015; Maimone et al., 2010) and solid lesions (Tummala, Junaidi, & Agarwal, 2011; Vukobrat-Bijedic et al., 2014) of the pancreas but there is still a lack of studies comparing the morphology and size of the anatomic segments of the pancreas, particu- larly for US. Due to advances in US technology and improved imaging quality this technique becomes more relevant for diagnostic and thera- peutic strategies (Engjom et al., 2017; Lerch et al., 1992; Poza-Cordon & Ripolles-Gonzalez, 2014; Sun et al., 2017). Therefore, a comparison with high resolution imaging methods such as CT or MRI with US is justified.
Cerebrovascular disease is a terrible medical and economic burden. Stroke, the most acute consequence of cerebrovascular disease, is a leading cause of death and disability in first world countries 1 . However, only about 10% of patients receive causal treatment, i.e. thrombolysis. On the other hand, developing chronic steno-occlusive disease, e.g. with atherosclerotic etiology or as an effect of Moya-Moya-Disease, is a diagnostic challenge, where only potentially harmful invasive diagnostic techniques are available to retrieve necessary diagnostic information. Consequently, diagnostic advances in cerebrovascular imaging are highly warranted. Neuroimaging plays a key role in this endeavor and magneticresonanceimaging (MRI) is a common neuroimaging method due to its inherent advantages: It is non-invasive, offers high spatial resolution and has no known long-lasting harmful effects on patients. Improved and new MRI neuroimaging methods have the potential a) to increase the validity of current diagnostic tools, b) to lead to new diagnostic tools and c) to replace current invasive and potentially risky diagnostic measures. The key question is, however, which diagnostic targets should be the aim of methodological advances. The international research community has developed a terminology to define diagnosis relevant imaging targets in acute stroke, so called “Treatment-Relevant Acute Imaging Targets” (TRAITS) 2 . These TRAITS serve as markers for inclusion or exclusion of patients into certain treatment protocols. This definition is beneficial, as it focuses imaging research on goals which are directly beneficial for patients. While TRAITS were predominantly developed for the use in acute stroke, a use in chronic forms of cerebrovascular disease such a steno-occlusive disease or Moya-Moya-disease is justified, as the imaging targets are similar. For the current thesis we defined three different TRAITS in three subprojects, where diagnostic improvements are warranted, and analyzed them in 7 publications:
Within the brain mapping community, the problem of validity and repeatability of functional neuroimaging results has recently become a major issue. In 2016, the Committee on Best Practice in Data Analysis and Sharing from the Organization for Human Brain Mapping (OHBM) created recommendations for replicable research in neuroimaging, focused on magneticresonanceimaging and functional magneticresonanceimaging (fMRI). Here, “replication” is defined as “Independent researchers use independent data and … methods to arrive at the same original conclusion.” “Repeatability” is defined as repeated investigations performed “with the same method on identical test/measurement items in the same test or measuring facility by the same operator using the same equipment within short intervals of time” (ISO 3534-2:2006 3.3.5). An intermediate position between replication and repeatability is defined for “reproducibility”: repeated investigations performed “with the same method on identical test/measurement items in different test or measurement facilities with different operators using different equipment” (ISO 3534-2:2006 3.3.10). Further definitions vary depending on the focus, be it the “measurement stability,” the “analytical stability,” or the “generaliz- ability” over subjects, labs, methods, or populations.
Chapter 3. Functional MagneticResonanceImaging (fMRI)
so-called fat suppression techniques (cf. section 8.2).
3.2.5. N/2 Ghost
A specific EPI artefact is the so called N/2 ghost caused by a misregistration between odd and even lines acquired. The N/2 ghost is a rather faint duplicate of the imaged object shifted by half the field-of-view. The intensity of the N/2 ghost is usually modulated by a sinosoidal signal profile in readout direction which reflects the phase difference corresponding to the shift between the k-space lines. Various methods have been proposed to correct for these ghosts, some of which do not even require a separate calibration scan. The most prevalent calibration method relies on the acquisition of two non-phase-encoded projections using a very short echo train immediately following excitation (and slice rewinding). Assuming, without loss of generality, the first readout is positive, the second, negative readout is usually followed by an additional third positive readout resulting in three projections with extrememly short echo time and thus very little phase evolution (almost no signal drop-outs, etc.). The first and the third projection, i.e. the Fourier transformed odd numbered signals, are averaged and the complex phase is compared to the complex phase of the second projection.The systematic phase difference can then be corrected for in the following imaging scans. Unless stated otherwise, for all results shown in this work a linear approximation of the phase (constant offset and slope) is used for phase correction. This leads to reasonable N/2 ghost reduction, at least at moderate field strengths of 3 Tesla. Alternative methods include non-linear phase correction and a pixel-by-pixel phase correction which can be computed from standard phase correction scans as well. A detailed discussion of these fundametal phase correction methods can be found in Ref. .
Independent component analysis is a method for blind signal separation formed on the basis of assumed statistical independence of the source signals. The problem of blind source sep- aration or blind signal separation (BSS) appears in many contexts. Blind source separation is a class of explorative tools originally developed for the analysis of images and sound. BSS has received wide attention in various fields such as speech enhancement, geophysical data processing, data mining, wireless communications, image processing, and biomedical signal analysis and processing (EEG, MEG, fMRI). The method is called ’blind’ because it aims to recover source signals from mixtures with unknown coefficients. The most simple situation occurs for two speakers speaking simultaneously. Imagine that the mixture of their voices reaches two microphones, and one wants to separate both sources such that each detector registers only one voice. The problem is called the cocktail party problem which can also be extended to N people standing around and chatting with each other. This mixture of signals is recorded by N microphones. Again, the aim is to extract the voices of the speaker (the sources) from the mixture of speech signals without knowing the sources and the mixture process assuming that the voices are independent of each other. In this project the problem of BSS is applied to the field of functional magneticresonanceimaging (fMRI), especially to fMRI time series, For the fMRI time series it is assumed that the measured signal of neuronal activity are mixed linearly with multiple other signals like noise or movement artifacts, contributing to the measurement. The aim of blind signal sep- aration in fMRI is to detect the intrinsic signals, i.e. the neuronal activity, from the mixed signals measured during the fMRI study. ICA is a statistical approach of transforming multidimensional data into components that are as independent of each other as possible.
Chapter 3. Functional MagneticResonanceImaging (fMRI)
so-called fat suppression techniques (cf. section 8.2).
3.2.5. N /2 Ghost
A specific EPI artefact is the so called N /2 ghost caused by a misregistration between odd and even lines acquired. The N /2 ghost is a rather faint duplicate of the imaged object shifted by half the field-of-view. The intensity of the N /2 ghost is usually modulated by a sinosoidal signal profile in readout direction which reflects the phase difference corresponding to the shift between the k-space lines. Various methods have been proposed to correct for these ghosts, some of which do not even require a separate calibration scan. The most prevalent calibration method relies on the acquisition of two non-phase-encoded projections using a very short echo train immediately following excitation (and slice rewinding). Assuming, without loss of generality, the first readout is positive, the second, negative readout is usually followed by an additional third positive readout resulting in three projections with extrememly short echo time and thus very little phase evolution (almost no signal drop-outs, etc.). The first and the third projection, i.e. the Fourier transformed odd numbered signals, are averaged and the complex phase is compared to the complex phase of the second projection.The systematic phase difference can then be corrected for in the following imaging scans. Unless stated otherwise, for all results shown in this work a linear approximation of the phase (constant offset and slope) is used for phase correction. This leads to reasonable N/2 ghost reduction, at least at moderate field strengths of 3 Tesla. Alternative methods include non-linear phase correction and a pixel-by-pixel phase correction which can be computed from standard phase correction scans as well. A detailed discussion of these fundametal phase correction methods can be found in Ref. .
The novel technique for phase-based quantitative conductivity mapping finds it application in brain tumour management, as demonstrated in Chapter 5. Furthermore, a novel method to estimate and quantify tissue sodium concentration in the brain in vivo which relies on MR-based electrical properties mapping (MR-EPT) is proposed in Chapter 6. To validate this approach, conductivity maps and sodium concentration maps of the brain (the latter one being based on sodium MRI) were estimated independently using state-of-the-art approaches in a group of 8 healthy adults. The so-called pseudo tissue sodium concentration (pTSC) maps derived from the conductivity map using the proposed model was compared with the “true” sodium concentration map (TSC) and the agreement between the two was studied. A statistically significant Pearson correlation (p<0.001; r=0.6) was observed between the two modalities while Bland-Altman analysis revealed a discrepancy of ~4mMol/L on average over the whole brain. This study suggests that pseudo tissue sodium concentration mapping could become a valuable alternative method to infer quantitative sodium concentration maps in the brain, and directions of improvements are discussed to lead to progress in this field, namely the possibility to include tissue water content to refine the model. A perspective technological application of this work is the possibility to estimate sodium concentration maps at sites where the necessary hardware for sodium MRI is not available. This work is revised and accepted in the journal “MagneticResonance in Medicine”. Consequently, Chapter 6 is an adaptation of the original article with modifications and unpublished results.
with in Chpt. 6. The theoretical background and the implemented algorithms for reconstruction of magnetic susceptibility distributions based on fieldmaps are described in Chpt. 7. The im- plemented algorithms from literature include closed-form and minimisation approaches. These approaches are validated and parameter optimisation is attempted. This chapter is followed by the investigation of background field influences observed in MRI fieldmaps (see Chpt. 8), including a detailed assessment of several background removal strategies. A novel approach, MUBAFIRE, is introduced, validated and qualitatively and quantitatively compared to other algorithms in Chpt. 9. MUBAFIRE is a multi-step technique that combines several models for background field correction in a sequential filter chain, whilst preserving the information required for susceptibility reconstruction. The last processing step addressed in this thesis is the recombination of phase data from multiple receive channels. Although this step is actually the very first in a computing chain, multichannel recombination is only necessary at high field strength, so the according chap- ter was placed in the end. Finally, a variety of applications for the phase imaging process including post mortem and in vivo measurements at 3 T and at 9.4 T are presented in Chpt. 11. Quanti- tative evaluation means and various measurement parametrisations are discussed and presented. Although all technical chapters contain examples for the application of the described methods, this last main chapter outlines the benefits and substantiates the applicability of the established phase imaging workflow with respect to the presented measurements.
7.4. RECONSTRUCTING SUSCEPTIBILITY DISTRIBUTIONS
7.4 Reconstructing Susceptibility Distributions
All strategies for estimating susceptibility distributions in soft tissue are based on the a priori estimation of fieldmaps, and thus on phase imaging. Single-echo GRE measurements are not useful for this aim, since fieldmaps derived of such data may contain deviations from the true field due to unconsidered phase offsets (see Section 6.1). Fieldmaps used for susceptibility recon- struction should at least rely on double-echo, or offset-corrected phase data. Furthermore it is evident, that the estimation of susceptibility requires knowledge of the magnetic field in all spatial dimensions. Ideally, an isotropic sampling of space should be attempted. This is best achieved using an isotropically sampled, full 3D GRE sequence with slab- or non-selective excitation. Sev- eral strategies for the reconstruction of tissue magnetic susceptibility were introduced during the last years. Two main categories can be defined, single and multiple orientation measurements. Furthermore, reconstruction can be performed directly or by using a minimisation approach. All methods presented below use the model of scalar susceptibility (Section 7.3.1), and will be shown in application examples using optimised parametrisation. Parameter optimisation will be discussed later on in Section 7.6. A comprehensive discussion of the current reconstruction techniques and applications for susceptibility imaging in MRI can be found in Reichenbach [ 2012 ].
In principle, cardiac T1 mapping using both approaches is not restricted to radial trajectories and gradient echo read out. The approach would gain clinical relevance by acquisition with bSSFP read out because higher SNR that is needed for lower field strength, since nowadays most clinical MRI examinations are performed on a 1.5 Tesla scanner. However, this implementation comes with challenges, such as magnetization transfer effect and T2 dependencies [ 14 ]. These effects have to be included into the model function and preliminary results can be found in [ C1 ]. Other trajectories that provide frequent coverage of low frequencies would be suitable for multiparametric imaging, such as spiral trajectories with golden radial ratio between two consecutive read outs, providing more information per read out line than radial spokes. Another option would be pseudo-random sampling along phase encoding, where compressed sensing with higher sampling rate of low frequencies for a good determination of the longitudinal magnetization during magnetization recovery and motion of the heart could be used instead of iterative SENSE reconstruction for faster image reconstruction.
In the previous sections we described the response of spins to an ex- ternal magnetic field and the resulting NMR signal. The described raw signal — the free induction decay — does not yield any infor- mation about the location of the spins. For the generation of an image one needs information on spin location. This information can be gained by using time–varying gradient fields. The gradient fields used in imaging are generally spatially linear varying magnetic fields which are superimposed on the static magnetic field. In an MRI scanner these fields are generated by electrical gradient coils driven by powerful amplifiers which enable a rapid switching of the gradi- ents. Compared to the magnetic field which is on the order of 1.5-3 Tesla for clinical scanners and up to 9.4 Tesla for state–of–the–art research instruments the magnetic field gradients have relatively low maximum field strengths usually on the order of 80 mT with gradient strengths of 40-80 mT m for whole body scanners.