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In this work, accelerated non-Cartesian Magnetic Resonance Imaging (MRI) methods were established and applied to cardiovascular imaging (CMR) at different magnetic field strengths (3T and 7T).
To enable rapid data acquisition, highly efficient spiral k-space trajectories were created. In addition, hybrid sampling patterns such as the twisting radial lines (TWIRL) k-space trajectory were studied.
Imperfections of the dynamic gradient system of a MR scanner result in k-space sampling errors. Ultimately, these errors can lead to image artifacts in non-Cartesian acquisitions.
Among other reasons such as an increased reconstruction complexity, they cause the lack of spiral sequences in clinical routine compared to standard Cartesian imaging.
Therefore, the Gradient System Transfer Functions (GSTFs) of both scanners were determined and used for k-space trajectory correction in post-correction as well as in terms of a pre-emphasis.
The GSTF pre-emphasis was implemented as a fully automatic procedure, which enabled a precise correction of arbitrary gradient waveforms for double-oblique slice orientations.
Consequently, artifacts due to trajectory errors could be mitigated, which resulted in high image quality in non-Cartesian MRI.
Additionally, the GSTF correction was validated by measuring pre-emphasized spiral gradient outputs, which showed high agreement with the theoretical gradient waveforms.
Furthermore, it could be demonstrated that the performance of the GSTF correction is superior to a simple delay compensation approach.
The developed pulse sequences were applied to gated as well as real-time CMR. Special focus lied on the implementation of a spiral imaging protocol to resolve the beating heart of animals and humans in real time and free breathing.
In order to achieve real-time CMR with high spatiotemporal resolution, k-space undersampling was performed. For this reason, efficient sampling strategies were developed with the aim to facilitate compressed sensing (CS) during image reconstruction.
The applied CS approach successfully removed aliasing artifacts and yielded high-resolution cardiac image series. Image reconstruction was performed offline in all cases such that the images were not available immediately after acquisition at the scanner.
Spiral real-time CMR could be performed in free breathing, which led to an acquisition time of less than 1 minute for a whole short-axis stack.
At 3T, the results were compared to the gold standard of electrocardiogram-gated Cartesian CMR in breath hold, which revealed similar values for important cardiovascular functional and volumetric parameters.
This paves the way to an application of the developed framework in clinical routine of CMR.
In addition, the spiral real-time protocol was transferred to swallowing and speech imaging at 3T, and first images were presented.
The results were of high quality and confirm the straightforward utilization of the spiral sequence in other fields of MRI.
In general, the GSTF correction yielded high-quality images at both field strengths, 3T and 7T.
Off-resonance related blurring was mitigated by applying non-Cartesian readout gradients of short duration. At 7T, however, B1-inhomogeneity led to image artifacts in some cases.
All in all, this work demonstrated great advances in accelerating the MRI process by combining efficient, undersampled non-Cartesian k-space coverage with CS reconstruction.
Trajectory correction using the GSTF can be implemented at any scanner model and enables non-Cartesian imaging with high image quality.
Especially MRI of dynamic processes greatly benefits from the presented rapid imaging approaches.
Magnetic Resonance Imaging (MRI) is a non-invasive medical imaging technique, that is rou- tinely used in clinical practice for detection and diagnosis of a wide range of different diseases. In MRI, no ionizing radiation is used, making even repeated application unproblematic. This is an important advantage over other common imaging methods such as X-rays and Computer To- mography. One major drawback of MRI, however, are long acquisition times and associated high costs of experiments. Since the introduction of MRI, several important technical developments have been made to successfully reduce acquisition times. In this work, novel approaches were developed to increase the efficiency of MRI acquisitions.
In Chapter 4, an improved radial turbo spin-echo (TSE) combined acquisition and reconstruction strategy was introduced. Cartesian turbo spin-echo sequences [3] are widely used especially for the detection and diagnosis of neurological pathologies, as they provide high SNR images with both clinically important proton density and T2 contrasts. TSE acquisitions combined with radial sampling are very efficient, since it is possible to obtain a number of ETL images with different contrasts from a single radial TSE measurement [56–58]. Conventionally, images with a particular contrast are obtained from both radial and Cartesian TSE acquisitions by combining data from different echo times into a single image. In the radial case, this can be achieved by employing k-space weighted image contrast (KWIC) reconstruction. In KWIC, the center region of k-space is filled exclusively with data belonging to the desired contrast while outer regions also are assembled with data acquired at other echo times. However, this data sharing leads to mixed contrast contributions to both Cartesian and radial TSE images. This is true especially for proton density weighted images and therefore may reduce their diagnostic value.
In the proposed method, an adapted golden angle reordering scheme is introduced for radial TSE acquisitions, that allows a free choice of the echo train length and provides high flexibility in image reconstruction. Unwanted contrast contaminations are greatly reduced by employing a narrow-band KWIC filter, that restricts data sharing to a small temporal window around the de- sired echo time. This corresponds to using fewer data than required for fully sampled images and consequently leads to images exhibiting aliasing artifacts. In a second step, aliasing-free images are obtained using parallel imaging. In the neurological examples presented, the CG-SENSE algorithm [42] was chosen due to its stable convergence properties and its ability to reconstruct arbitrarily sampled data. In simulations as well as in different in vivo neurological applications, no unwanted contrast contributions could be observed in radial TSE images reconstructed with the proposed method. Since this novel approach is easy to implement on today’s scanners and requires low computational power, it might be valuable for the clinical breakthrough of radial TSE acquisitions.
In Chapter 5, an auto-calibrating method was introduced to correct for stimulated echo contribu- tions to T2 estimates from a mono-exponential fit of multi spin-echo (MSE) data. Quantification of T2 is a useful tool in clinical routine for the detection and diagnosis of diseases as well as for tis- sue characterization. Due to technical imperfections, refocusing flip angles in a MSE acquisition deviate from the ideal value of 180○. This gives rise to significant stimulated echo contributions to the overall signal evolution. Therefore, T2 estimates obtained from MSE acquisitions typically are notably higher than the reference. To obtain accurate T2 estimates from MSE acquisitions, MSE signal amplitudes can be predicted using the extended phase graph (EPG, [23, 24]) algo- rithm. Subsequently, a correction factor can be obtained from the simulated EPG T2 value and applied to the MSE T2 estimates. However, EPG calculations require knowledge about refocus- ing pulse amplitudes, T2 and T1 values and the temporal spacing of subsequent echoes. While the echo spacing is known and, as shown in simulations, an approximate T1 value can be assumed for high ratios of T1/T2 without compromising accuracy of the results, the remaining two parameters are estimated from the data themselves. An estimate for the refocusing flip angle can be obtained from the signal intensity ratio of the second to the first echo using EPG. A conventional mono- exponential fit of the MSE data yields a first estimate for T2. The T2 correction is then obtained iteratively by updating the T2 value used for EPG calculations in each step. For all examples pre- sented, two iterations proved to be sufficient for convergence. In the proposed method, a mean flip angle is extracted across the slice. As shown in simulations, this assumption leads to greatly reduced deviations even for more inhomogeneous slice profiles. The accuracy of corrected T2 values was shown in experiments using a phantom consisting of bottles filled with liquids with a wide range of different T2 values. While T2 MSE estimates were shown to deviate significantly from the spin-echo reference values, this is not the case for corrected T2 values. Furthermore, applicability was demonstrated for in vivo neurological experiments.
In Chapter 6, a new auto-calibrating parallel imaging method called iterative GROG was pre- sented for the reconstruction of non-Cartesian data. A wide range of different non-Cartesian schemes have been proposed for data acquisition in MRI, that present various advantages over conventional Cartesian sampling such as faster acquisitions, improved dynamic imaging and in- trinsic motion correction. However, one drawback of non-Cartesian data is the more complicated reconstruction, which is ever more problematic for non-Cartesian parallel imaging techniques. Iterative GROG uses Calibrationless Parallel Imaging by Structured Low-Rank Matrix Completion (CPI) for data reconstruction. Since CPI requires points on a Cartesian grid, it cannot be used to directly reconstruct non-Cartesian data. Instead, Grappa Operator Gridding (GROG) is employed in a first step to move the non-Cartesian points to the nearest Cartesian grid locations. However, GROG requires a fully sampled center region of k-space for calibration. Combining both methods in an iterative scheme, accurate GROG weights can be obtained even from highly undersampled non-Cartesian data. Subsequently, CPI can be used to reconstruct either full k- space or a calibration area of arbitrary size, which can then be employed for data reconstruction with conventional parallel imaging methods.
In Chapter 7, a new 2D sampling scheme was introduced consisting of multiple oscillating effi- cient trajectories (MOET), that is optimized for Compressed Sensing (CS) reconstructions. For successful CS reconstruction of a particular data set, some requirements have to be met. First, ev- ery data sample has to carry information about the whole object, which is automatically fulfilled for the Fourier sampling employed in MRI. Additionally, the image to be reconstructed has to be sparse in an arbitrary domain, which is true for a number of different applications. Last, data sam- pling has to be performed in an incoherent fashion. For 2D imaging, this important requirement of CS is difficult to achieve with conventional Cartesian and non-Cartesian sampling schemes. Ra- dial sampling is often used for CS reconstructions of dynamic data despite the streaking present in undersampled images. To obtain incoherent aliasing artifacts in undersampled images while at the same time preserving the advantages of radial sampling for dynamic imaging, MOET com- bines radial spokes with oscillating gradients of varying amplitude and alternating orientation orthogonal to the readout direction. The advantage of MOET over radial sampling in CS re- constructions was demonstrated in simulations and in in vivo cardiac imaging. MOET provides superior results especially when used in CS reconstructions with a sparsity constraint directly in image space. Here, accurate results could be obtained even from few MOET projections, while the coherent streaking artifacts present in the case of radial sampling prevent image recovery even for smaller acceleration factors. For CS reconstructions of dynamic data with sparsity constraint in xf-space, the advantage of MOET is smaller since the temporal reordering is responsible for an important part of incoherency. However, as was shown in simulations of a moving phantom and in the reconstruction of ungated cardiac data, the additional spatial incoherency provided by MOET still leads to improved results with higher accuracy and may allow reconstructions with higher acceleration factors.
The relation between LV function and cardiac MRI tissue characteristics in separate myocardial segments and their change over time has yet to be explored in myocarditis. Thus, our research aimed to investigate possible associations between global and regional myocardial T1 and T2 times and peak strain in patients with suspected myocarditis.
From 2012 to 2015, 129 patients with clinically suspected myocarditis of the prospective, observational MyoRacer-Trial underwent systematic biventricular EMB at baseline and cardiac MRI at baseline and after three months as a follow-up. We divided the LV myocardium into 17 segments and estimated the segmental myocardial strain using FT. We registered T1 and T2 maps to the cine sequences and transferred the segmentations used for FT to ensure conformity of the myocardial segments. Multi-level multivariable linear mixed effects regression was applied to investigate the relation of segmental myocardial strain to relaxation times and their respective change from baseline to follow-up.
We found a significant improvement in myocardial peak strain from baseline to follow-up (p < 0.001; all p-values given for likelihood ratio tests) and significant associations between higher T1 and T2 times and lower segmental myocardial peak strain (p ranging from < 0.001 to 0.049). E.g., regression coefficient (Reg. coef.) for segmental radial peak strain in short axis view (SRPS_SAX) and T1 time: -1.9, 95% CI (-2.6;-1.2) %/100 ms, p < 0.001. A decrease in T1 and T2 times from baseline to follow-up was also significantly related to a recovery of segmental peak strains (p ranging from < 0.001 to 0.050). E.g., Reg. coef. for SRPS_SAX per ΔT1: -1.8, 95% CI (-2.5;-1.0) %/100 ms, p < 0.001. Moreover, the higher the baseline T1 time, the more substantial the functional recovery from baseline to follow-up (p ranging from 0.004 to 0.042, e.g., for SRPS_SAX: Reg. coef. 1.3, 95% CI (0.4;2.1) %/100 ms, p 0.004). We did not find an effect modification by the presence of myocarditis in the EMB (p > 0.1).
Our cross-sectional and longitudinal analyses provide evidence of dose-dependent correlations between T1 and T2 relaxation times and myocardial peak strain in patients with clinical presentation of myocarditis, regardless of the EMB result. Thus, assessing strain values and mapping relaxation times helps estimate the functional prognosis in patients with clinically suspected myocarditis.
Purpose
The AMADEUS (Area Measurement And DEpth and Underlying Structures) scoring and grading system has been proposed for the MRI based evaluation of untreated focal chondral defects around the knee. The clinical practicability, its correlation with arthroscopically assessed grading systems (ICRS – International Cartilage Repair Society) and thereby its clinical value in terms of decision making and guiding prognosis was yet to determine.
Methods
From 2008 to 2019 a total of 89 individuals were indicated for high tibial valgus osteotomy (HTO) due to tibial varus deformity and concomitant chondral defects of the medial compartment of the knee. All patients received a preoperative MRI (1.5 Tesla or 3.0 Tesla) and pre-osteotomy diagnostic arthroscopy. Chondral defects of the medial compartment were scored and graded with the MRI based AMADEUS by three independent raters and compared to arthroscopic defect grading by the ICRS system. Interrater and intrarater reliability as well as correlation analysis with the ICRS classification system were assessed.
Results
Intraclass correlation coefficients for the various subscores of the AMADEUS showed an overall good to excellent interrater agreement (min: 0.26, max: 0.80). Intrarater agreement turned out to be substantially inferior (min: 0.08, max: 0.53). Spearman correlation revealed an overall moderate correlative association of the AMADEUS subscores with the ICRS classification system, apart from the defect area subscore. Sensitivity of the AMADEUS to accurately identify defect severity according to the ICRS was 0.7 (0.69 for 3.0 Tesla MRI, 0.67 for 1.5 Tesla MRI). The mean AMADEUS grade was 2.60 ± 0.81 and the mean ICRS score 2.90 ± 0.63.
Conclusions
Overall, the AMADEUS with all its subscores shows moderate correlation with the arthroscopic chondral grading system according to ICRS. This suggests that chondral defect grading by means of the MRI based AMADEUS is well capable of influencing and guiding treatment decisions. Interrater reliability shows overall good agreement.
Within this thesis, three main approaches for the assessment and investigation of altered hemodynamics like wall shear stress, oscillatory shear index and the arterial pulse wave velocity in atherosclerosis development and progression were conducted:
1. The establishment of a fast method for the simultaneous assessment of 3D WSS and PWV in the complete murine aortic arch via high-resolution 4D-flow MRI
2. The utilization of serial in vivo measurements in atherosclerotic mouse models using high-resolution 4D-flow MRI, which were divided into studies describing altered hemodynamics in late and early atherosclerosis
3. The development of tissue-engineered artery models for the controllable application and variation of hemodynamic and biologic parameters, divided in native artery models and biofabricated artery models, aiming for the investigation of the relationship between atherogenesis and hemodynamics
Chapter 2 describes the establishment of a method for the simultaneous measurement of 3D WSS and PWV in the murine aortic arch at, using ultra high-field MRI at 17.6T [16], based on the previously published method for fast, self-navigated wall shear stress measurements in the murine aortic arch using radial 4D-phase contrast MRI at 17.6 T [4]. This work is based on the collective work of Dr. Patrick Winter, who developed the method and the author of this thesis, Kristina Andelovic, who performed the experiments and statistical analyses. As the method described in this chapter is basis for the following in vivo studies and undividable into the sub-parts of the contributors without losing important information, this chapter was not split into the single parts to provide fundamental information about the measurement and analysis methods and therefore better understandability for the following studies. The main challenge in this chapter was to overcome the issue of the need for a high spatial resolution to determine the velocity gradients at the vascular wall for the WSS quantification and a high temporal resolution for the assessment of the PWV without prolonging the acquisition time due to the need for two separate measurements. Moreover, for a full coverage of the hemodynamics in the murine aortic arch, a 3D measurement is needed, which was achieved by utilization of retrospective navigation and radial trajectories, enabling a highly flexible reconstruction framework to either reconstruct images at lower spatial resolution and higher frame rates for the acquisition of the PWV or higher spatial resolution and lower frame rates for the acquisition of the 3D WSS in a reasonable measurement time of only 35 minutes. This enabled the in vivo assessment of all relevant hemodynamic parameters related to atherosclerosis development and progression in one experimental session. This method was validated in healthy wild type and atherosclerotic Apoe-/- mice, indicating no differences in robustness between pathological and healthy mice.
The heterogeneous distribution of plaque development and arterial stiffening in atherosclerosis [10, 12], however, points out the importance of local PWV measurements. Therefore, future studies should focus on the 3D acquisition of the local PWV in the murine aortic arch based on the presented method, in order to enable spatially resolved correlations of local arterial stiffness with other hemodynamic parameters and plaque composition.
In Chapter 3, the previously established methods were used for the investigation of changing aortic hemodynamics during ageing and atherosclerosis in healthy wild type and atherosclerotic Apoe-/- mice using the previously established methods [4, 16] based on high-resolution 4D-flow MRI. In this work, serial measurements of healthy and atherosclerotic mice were conducted to track all changes in hemodynamics in the complete aortic arch over time. Moreover, spatially resolved 2D projection maps of WSS and OSI of the complete aortic arch were generated. This important feature allowed for the pixel-wise statistical analysis of inter- and intragroup hemodynamic changes over time and most importantly – at a glance. The study revealed converse differences of local hemodynamic profiles in healthy WT and atherosclerotic Apoe−/− mice, with decreasing longWSS and increasing OSI, while showing constant PWV in healthy mice and increasing longWSS and decreasing OSI, while showing increased PWV in diseased mice. Moreover, spatially resolved correlations between WSS, PWV, plaque and vessel wall characteristics were enabled, giving detailed insights into coherences between hemodynamics and plaque composition. Here, the circWSS was identified as a potential marker of plaque size and composition in advanced atherosclerosis. Moreover, correlations with PWV values identified the maximum radStrain could serve as a potential marker for vascular elasticity. This study demonstrated the feasibility and utility of high-resolution 4D flow MRI to spatially resolve, visualize and analyze statistical differences in all relevant hemodynamic parameters over time and between healthy and diseased mice, which could significantly improve our understanding of plaque progression towards vulnerability. In future studies the relation of vascular elasticity and radial strain should be further investigated and validated with local PWV measurements and CFD.
Moreover, the 2D histological datasets were not reflecting the 3D properties and regional characteristics of the atherosclerotic plaques. Therefore, future studies will include 3D plaque volume and composition analysis like morphological measurements with MRI or light-sheet microscopy to further improve the analysis of the relationship between hemodynamics and atherosclerosis.
Chapter 4 aimed at the description and investigation of hemodynamics in early stages of atherosclerosis. Moreover, this study included measurements of hemodynamics at baseline levels in healthy WT and atherosclerotic mouse models. Due to the lack of hemodynamic-related studies in Ldlr-/- mice, which are the most used mouse models in atherosclerosis research together with the Apoe-/- mouse model, this model was included in this study to describe changing hemodynamics in the aortic arch at baseline levels and during early atherosclerosis development and progression for the first time. In this study, distinct differences in aortic geometries of these mouse models at baseline levels were described for the first time, which result in significantly different flow- and WSS profiles in the Ldlr-/- mouse model. Further basal characterization of different parameters revealed only characteristic differences in lipid profiles, proving that the geometry is highly influencing the local WSS in these models. Most interestingly, calculation of the atherogenic index of plasma revealed a significantly higher risk in Ldlr-/- mice with ongoing atherosclerosis development, but significantly greater plaque areas in the aortic arch of Apoe-/- mice. Due to the given basal WSS and OSI profile in these two mouse models – two parameters highly influencing plaque development and progression – there is evidence that the regional plaque development differs between these mouse models during very early atherogenesis.
Therefore, future studies should focus on the spatiotemporal evaluation of plaque development and composition in the three defined aortic regions using morphological measurements with MRI or 3D histological analyses like LSFM. Moreover, this study offers an excellent basis for future studies incorporating CFD simulations, analyzing the different measured parameter combinations (e.g., aortic geometry of the Ldlr-/- mouse with the lipid profile of the Apoe-/- mouse), simulating the resulting plaque development and composition. This could help to understand the complex interplay between altered hemodynamics, serum lipids and atherosclerosis and significantly improve our basic understanding of key factors initiating atherosclerosis development.
Chapter 5 describes the establishment of a tissue-engineered artery model, which is based on native, decellularized porcine carotid artery scaffolds, cultured in a MRI-suitable bioreactor-system [23] for the investigation of hemodynamic-related atherosclerosis development in a controllable manner, using the previously established methods for WSS and PWV assessment [4, 16]. This in vitro artery model aimed for the reduction of animal experiments, while simultaneously offering a simplified, but completely controllable physical and biological environment. For this, a very fast and gentle decellularization protocol was established in a first step, which resulted in porcine carotid artery scaffolds showing complete acellularity while maintaining the extracellular matrix composition, overall ultrastructure and mechanical strength of native arteries. Moreover, a good cellular adhesion and proliferation was achieved, which was evaluated with isolated human blood outgrowth endothelial cells. Most importantly, an MRI-suitable artery chamber was designed for the simultaneous cultivation and assessment of high-resolution 4D hemodynamics in the described artery models. Using high-resolution 4D-flow MRI, the bioreactor system was proven to be suitable to quantify the volume flow, the two components of the WSS and the radStrain as well as the PWV in artery models, with obtained values being comparable to values found in literature for in vivo measurements. Moreover, the identification of first atherosclerotic processes like intimal thickening is achievable by three-dimensional assessment of the vessel wall morphology in the in vitro models. However, one limitation is the lack of a medial smooth muscle cell layer due to the dense ECM. Here, the utilization of the laser-cutting technology for the generation of holes and / or pits on a microscale, eventually enabling seeding of the media with SMCs showed promising results in a first try and should be further investigated in future studies. Therefore, the proposed artery model possesses all relevant components for the extension to an atherosclerosis model which may pave the way towards a significant improvement of our understanding of the key mechanisms in atherogenesis.
Chapter 6 describes the development of an easy-to-prepare, low cost and fully customizable artery model based on biomaterials. Here, thermoresponsive sacrificial scaffolds, processed with the technique of MEW were used for the creation of variable, biomimetic shapes to mimic the geometric properties of the aortic arch, consisting of both, bifurcations and curvatures. After embedding the sacrificial scaffold into a gelatin-hydrogel containing SMCs, it was crosslinked with bacterial transglutaminase before dissolution and flushing of the sacrificial scaffold. The hereby generated channel was subsequently seeded with ECs, resulting in an easy-to-prepare, fast and low-cost artery model. In contrast to the native artery model, this model is therefore more variable in size and shape and offers the possibility to include smooth muscle cells from the beginning. Moreover, a custom-built and highly adaptable perfusion chamber was designed specifically for the scaffold structure, which enabled a one-step creation and simultaneously offering the possibility for dynamic cultivation of the artery models, making it an excellent basis for the development of in vitro disease test systems for e.g., flow-related atherosclerosis research. Due to time constraints, the extension to an atherosclerosis model could not be achieved within the scope of this thesis. Therefore, future studies will focus on the development and validation of an in vitro atherosclerosis model based on the proposed bi- and three-layered artery models.
In conclusion, this thesis paved the way for a fast acquisition and detailed analyses of changing hemodynamics during atherosclerosis development and progression, including spatially resolved analyses of all relevant hemodynamic parameters over time and in between different groups. Moreover, to reduce animal experiments, while gaining control over various parameters influencing atherosclerosis development, promising artery models were established, which have the potential to serve as a new platform for basic atherosclerosis research.
Objective
Growing interest in measuring the cochlear duct length (CDL) has emerged, since it can influence the selection of cochlear implant electrodes. Currently the measurements are performed with ionized radiation imaging. Only a few studies have explored CDL measurements in magnetic resonance imaging (MRI). Therefore, the presented study aims to fill this gap by estimating CDL in MRI and comparing it with multislice computed tomography (CT).
Study Design
Retrospective data analyses of 42 cochleae.
Setting
Tertiary care medical center.
Methods
Diameter (A value) and width (B value) of the cochlea were measured in HOROS software. The CDL and the 2-turn length were determined by the elliptic circular approximation (ECA). In addition, the CDL, the 2-turn length, and the angular length were determined via HOROS software by the multiplanar reconstruction (MPR) method.
Results
CDL values were significantly shorter in MRI by MPR (d = 1.38 mm, P < .001) but not by ECA. Similar 2-turn length measurements were significantly lower in MRI by MPR (d = 1.67 mm) and ECA (d = 1.19 mm, both P < .001). In contrast, angular length was significantly higher in MRI (d = 26.79°, P < .001). When the values were set in relation to the frequencies of the cochlea, no clinically relevant differences were estimated (58 Hz at 28-mm CDL).
Conclusion
In the presented study, CDL was investigated in CT and MRI by using different approaches. Since no clinically relevant differences were found, diagnostics with radiation may be omitted prior to cochlear implantation; thus, a concept of radiation-free cochlear implantation could be established.
Background
The Goutallier Classification is a semi quantitative classification system to determine the amount of fatty degeneration in rotator cuff muscles. Although initially proposed for axial computer tomography scans it is currently applied to magnet-resonance-imaging-scans. The role for its clinical use is controversial, as the reliability of the classification has been shown to be inconsistent. The purpose of this study was to compare the semi quantitative MRI-based Goutallier Classification applied by 5 different raters to experimental MR spectroscopic quantitative fat measurement in order to determine the correlation between this classification system and the true extent of fatty degeneration shown by spectroscopy.
Methods
MRI-scans of 42 patients with rotator cuff tears were examined by 5 shoulder surgeons and were graduated according to the MRI-based Goutallier Classification proposed by Fuchs et al. Additionally the fat/water ratio was measured with MR spectroscopy using the experimental SPLASH technique. The semi quantitative grading according to the Goutallier Classification was statistically correlated with the quantitative measured fat/water ratio using Spearman’s rank correlation.
Results
Statistical analysis of the data revealed only fair correlation of the Goutallier Classification system and the quantitative fat/water ratio with R = 0.35 (p < 0.05). By dichotomizing the scale the correlation was 0.72. The interobserver and intraobserver reliabilities were substantial with R = 0.62 and R = 0.74 (p < 0.01).
Conclusion
The correlation between the semi quantitative MRI based Goutallier Classification system and MR spectroscopic fat measurement is weak. As an adequate estimation of fatty degeneration based on standard MRI may not be possible, quantitative methods need to be considered in order to increase diagnostic safety and thus provide patients with ideal care in regard to the amount of fatty degeneration. Spectroscopic MR measurement may increase the accuracy of the Goutallier classification and thus improve the prediction of clinical results after rotator cuff repair. However, these techniques are currently only available in an experimental setting.
Background
Functional lung MRI techniques are usually associated with time-consuming post-processing, where manual lung segmentation represents the most cumbersome part. The aim of this study was to investigate whether deep learning-based segmentation of lung images which were scanned by a fast UTE sequence exploiting the stack-of-spirals trajectory can provide sufficiently good accuracy for the calculation of functional parameters.
Methods
In this study, lung images were acquired in 20 patients suffering from cystic fibrosis (CF) and 33 healthy volunteers, by a fast UTE sequence with a stack-of-spirals trajectory and a minimum echo-time of 0.05 ms. A convolutional neural network was then trained for semantic lung segmentation using 17,713 2D coronal slices, each paired with a label obtained from manual segmentation. Subsequently, the network was applied to 4920 independent 2D test images and results were compared to a manual segmentation using the Sørensen–Dice similarity coefficient (DSC) and the Hausdorff distance (HD). Obtained lung volumes and fractional ventilation values calculated from both segmentations were compared using Pearson’s correlation coefficient and Bland Altman analysis.
To investigate generalizability to patients outside the CF collective, in particular to those exhibiting larger consolidations inside the lung, the network was additionally applied to UTE images from four patients with pneumonia and one with lung cancer.
Results
The overall DSC for lung tissue was 0.967 ± 0.076 (mean ± standard deviation) and HD was 4.1 ± 4.4 mm. Lung volumes derived from manual and deep learning based segmentations as well as values for fractional ventilation exhibited a high overall correlation (Pearson’s correlation coefficent = 0.99 and 1.00). For the additional cohort with unseen pathologies / consolidations, mean DSC was 0.930 ± 0.083, HD = 12.9 ± 16.2 mm and the mean difference in lung volume was 0.032 ± 0.048 L.
Conclusions
Deep learning-based image segmentation in stack-of-spirals based lung MRI allows for accurate estimation of lung volumes and fractional ventilation values and promises to replace the time-consuming step of manual image segmentation in the future.
AimIn PET imaging, the different types of radiotracers and accumulations, as well as the diversity of disease patterns, make the analysis of molecular imaging data acquired in vivo challenging. Here, we evaluate and validate a semi-automated MRI template-based data analysis tool that allows preclinical PET images to be aligned to a self-created PET template. Based on the user-defined volume-of-interest (VOI), image data can then be evaluated using three different semi-quantitative parameters: normalized activity, standardized uptake value, and uptake ratio.
Materials and MethodsThe nuclear medicine Data Processing Analysis tool (NU_DPA) was implemented in Matlab. Testing and validation of the tool was performed using two types of radiotracers in different kinds of stroke-related brain diseases in rat models. The radiotracers used are 2-[\(^{18}\)F]fluoro-2-deoxyglucose ([\(^{18}\)F]FDG), a metabol\(^{68}\)Ga]Ga-Fucoidan, a target-selective radioligand specifically binding to p-selectin. After manual image import, the NU_DPA tool automatically creates an averaged PET template out of the acquired PET images, to which all PET images are then aligned onto. The added MRI template-based information, resized to the lower PET resolution, defines the VOI and also allows a precise subdivision of the VOI into individual sub-regions. The aligned PET images can then be evaluated semi-quantitatively for all regions defined in the MRI atlas. In addition, a statistical analysis and evaluation of the semi-quantitative parameters can then be performed in the NU_DPA tool.
ResultsUsing ischemic stroke data in Wistar rats as an example, the statistical analysis of the tool should be demonstrated. In this [\(^{18}\)F]FDG-PET experiment, three different experimental states were compared: healthy control state, ischemic stroke without electrical stimulation, ischemic stroke with electrical stimulation. Thereby, statistical data evaluation using the NU_DPA tool showed that the glucose metabolism in a photothrombotic lesion can be influenced by electrical stimulation.
ConclusionOur NU_DPA tool allows a very flexible data evaluation of small animal PET data in vivo including statistical data evaluation. Using the radiotracers [\(^{18}\)F]FDG and [\(^{68}\)Ga]Ga-Fucoidan, it was shown that the semi-automatic MRI-template based data analysis of the NU_DPA tool is potentially suitable for both metabolic radiotracers as well as target-selective radiotracers.
Magnetic resonance imaging (MRI) is a medical imaging method that involves no ionizing radiation and can be used non-invasively. Another important - if not the most important - reason for the widespread and increasing use of MRI in clinical practice is its interesting and highly flexible image contrast, especially of biological tissue. The main disadvantages of MRI, compared to other widespread imaging modalities like computed tomography (CT), are long measurement times and the directly resulting high costs. In the first part of this work, a new technique for accelerated MRI parameter mapping using a radial IR TrueFISP sequence is presented. IR TrueFISP is a very fast method for the simultaneous quantification of proton density, the longitudinal relaxation time T1, and the transverse relaxation time T2. Chapter 2 presents speed improvements to the original IR TrueFISP method. Using a radial view-sharing technique, it was possible to obtain a full set of relaxometry data in under 6 s per slice. Furthermore, chapter 3 presents the investigation and correction of two major sources of error of the IR TrueFISP method, namely magnetization transfer and imperfect slice profiles. In the second part of this work, a new MRI thermometry method is presented that can be used in MRI-safety investigations of medical implants, e.g. cardiac pacemakers and implantable cardioverter-defibrillators (ICDs). One of the major safety risks associated with MRI examinations of pacemaker and ICD patients is RF induced heating of the pacing electrodes. The design of MRI-safe (or MRI-conditional) pacing electrodes requires elaborate testing. In a first step, many different electrode shapes, electrode positions and sequence parameters are tested in a gel phantom with its geometry and conductivity matched to a human body. The resulting temperature increase is typically observed using temperature probes that are placed at various positions in the gel phantom. An alternative to this local thermometry approach is to use MRI for the temperature measurement. Chapter 5 describes a new approach for MRI thermometry that allows MRI thermometry during RF heating caused by the MRI sequence itself. Specifically, a proton resonance frequency (PRF) shift MRI thermometry method was combined with an MR heating sequence. The method was validated in a gel phantom, with a copper wire serving as a simple model for a medical implant.
Stroke, after myocardial infarction and cancer is the third most common cause of death worldwide and 1/6th of all human beings will suffer at least one stroke in their lives. Furthermore, it is the leading cause for adult disability with approximately one third of patients who survive for the next 6 months are dependent on others. Because of its huge socioeconomic burden absorbing 6% of all health care budgets and with the fact that life expectancy increases globally, one can assume that stroke is already, and will continue to be, the most challenging disease. Ischemic stroke accounts for approximately 80% of all strokes and results from a thrombotic or embolic occlusion of a major cerebral artery (most often the middle cerebral artery, MCA) or its branches Following acute ischemic stroke, the most worrisome outcome is the rapidly increasing intra-cranial pressure due to the formation of space-occupying vasogenic oedema which can have lethal consequences. Permeability changes at the Blood-Brain Barrier (BBB) usually accompanies the oedematous development and their time course can provide invaluable insight into the nature of the insult, activation of compensatory mechanisms followed by long term repair. Rodent models of focal cerebral ischemia have been developed and optimized to mimic human stroke conditions and serve as indispensable tools in the field of stroke research. The presented work constituting of three separate but complete works by themselves are sequential, where, the first part was dedicated to the establishment of non-invasive small animal imaging strategies on a 3 tesla clinical magnetic resonance scanner. This facilitated the longitudinal monitoring of pathological outcomes following stroke where identical animals can serve as its own control. Tissue relaxometric estimations were carried out initially to derive the transverse (T2), longitudinal (T1) and the transverse relaxation time due to magnetic susceptibility effects (T2*) at the cortical and striatal regions of the rodent brain. Statistically significant differences in T2*-values could be found between the cortex and striatal regions of the rodent brain. The derived tissue relaxation values were considered to modify the existing imaging protocols to facilitate the study of the rodent model of ischemic stroke. The modified sequence protocols adequately characterized all the clinically relevant sequels following acute ischemic stroke, like, the altered perfusion and diffusion characteristics. Subsequent to this, serial magnetic resonance imaging was performed to investigate the temporal and spatial relationship between the biphasic nature of BBB opening and, in parallel, the oedema formation after I/R injury in rats. T2-relaxometry for oedema assessment was performed at 1 h after ischemia, immediately following reperfusion, and at 4, 24 and 48 hours post reperfusion. Post-contrast T1-weighted imaging was performed at the last three time points to assess BBB integrity. The biphasic course of BBB opening with significant reduction in BBB permeability at 24 hours after reperfusion was associated with a progressive expansion of leaky BBB volume, accompanied by a peak ipsilateral oedema formation. At 48 hours, the reduction in T2-value indicated oedema resorption accompanied by a second phase of BBB opening. In addition, at 4 hours after reperfusion, oedema formation could also be detected at the contralateral striatum which persisted to varying degrees throughout the study, indicative of widespread effects of I/R injury. The observations of this study may indicate a dynamic temporal shift in the mechanisms responsible for biphasic BBB permeability changes, with non-linear relations to oedema formation. Two growth factor peptides namely pigment epithelium derived factor (PEDF) and epidermal growth factor (EGF) with widely different trophic properties were considered for their beneficial effects, if any, in the established rodent model of I/R injury and studied up to one week employing magnetic resonance imaging. Both the selected, trophic factors demonstrated significant neuroprotection as demonstrated by a reduction in infarct volume, even though PEDF was found to be the most potent one. PEDF also demonstrated significant attenuation of oedema formation in comparison to both the control and EGF groups, even though EGF could also demonstrate oedema suppression. In the present work, we noticed that interventions with macromolecule protein/peptides by itself could mediate remote oedema at distant sites even though the significance of such an observation is not clear at present. Susceptibility (T2*) weighted tissue relaxometric estimations were considered at the infarct region to detect any metabolic changes arising out of any neuroprotection and/or cellular proliferation / neurogenesis. PEDF group demonstrated a striking reduction of the T2*-values, which is indicative of an increased metabolic activity. Moreover, all the groups (Control, EGF and PEDF) demonstrated significantly elevated T2*-values at the contralateral striatum, which is indicative of widespread metabolic suppression usually associated with a variety of traumatic brain conditions. Moreover, as expected from the properties of PEDF, it demonstrated an extended BBB permeability suppression throughout the duration of the study. This study underlines the merits of considering non-invasive imaging strategies without which it was not possible to study the required parameters in a longitudinal fashion. All the observations are adequately supported by reasonably well defined mechanisms and needs to be further verified and confirmed by an immunohistochemical study. These results also need to be complemented by a functional study to evaluate the behavioural outcome of animals following these treatments. These studies are progressing at our laboratory and the results will be duly published afterwards.
Direct cooling of the catheter tip increases safety for CMR-guided electrophysiological procedures
(2012)
Background: One of the safety concerns when performing electrophysiological (EP) procedures under magnetic resonance (MR) guidance is the risk of passive tissue heating due to the EP catheter being exposed to the radiofrequency (RF) field of the RF transmitting body coil. Ablation procedures that use catheters with irrigated tips are well established therapeutic options for the treatment of cardiac arrhythmias and when used in a modified mode might offer an additional system for suppressing passive catheter heating.
Methods: A two-step approach was chosen. Firstly, tests on passive catheter heating were performed in a 1.5 T Avanto system (Siemens Healthcare Sector, Erlangen, Germany) using a ASTM Phantom in order to determine a possible maximum temperature rise. Secondly, a phantom was designed for simulation of the interface between blood and the vascular wall. The MR-RF induced temperature rise was simulated by catheter tip heating via a standard ablation generator. Power levels from 1 to 6 W were selected. Ablation duration was 120 s with no tip irrigation during the first 60 s and irrigation at rates from 2 ml/min to 35 ml/min for the remaining 60 s (Biotronik Qiona Pump, Berlin, Germany). The temperature was measured with fluoroscopic sensors (Luxtron, Santa Barbara, CA, USA) at a distance of 0 mm, 2 mm, 4 mm, and 6 mm from the catheter tip. Results: A maximum temperature rise of 22.4 degrees C at the catheter tip was documented in the MR scanner. This temperature rise is equivalent to the heating effect of an ablator's power output of 6 W at a contact force of the weight of 90 g (0.883 N). The catheter tip irrigation was able to limit the temperature rise to less than 2 degrees C for the majority of examined power levels, and for all examined power levels the residual temperature rise was less than 8 degrees C.
Conclusion: Up to a maximum of 22.4 degrees C, the temperature rise at the tissue surface can be entirely suppressed by using the catheter's own irrigation system. The irrigated tip system can be used to increase MR safety of EP catheters by suppressing the effects of unwanted passive catheter heating due to RF exposure from the MR scanner.
Background
Human cerebral small vessel disease (CSVD) has distinct histopathologic and imaging findings in its advanced stages. In spontaneously hypertensive stroke-prone rats (SHRSP), a well-established animal model of CSVD, we recently demonstrated that cerebral microangiopathy is initiated by early microvascular dysfunction leading to the breakdown of the blood–brain barrier and an activated coagulatory state resulting in capillary and arteriolar erythrocyte accumulations (stases). In the present study, we investigated whether initial microvascular dysfunction and other stages of the pathologic CSVD cascade can be detected by serial magnetic resonance imaging (MRI).
Findings
Fourteen SHRSP and three control (Wistar) rats (aged 26–44 weeks) were investigated biweekly by 3.0 Tesla (3 T) MRI. After perfusion, brains were stained with hematoxylin–eosin and histology was correlated with MRI data. Three SHRSP developed terminal CSVD stages including cortical, hippocampal, and striatal infarcts and macrohemorrhages, which could be detected consistently by MRI. Corresponding histology showed small vessel thromboses and increased numbers of small perivascular bleeds in the infarcted areas. However, 3 T MRI failed to visualize intravascular erythrocyte accumulations, even in those brain regions with the highest densities of affected vessels and the largest vessels affected by stases, as well as failing to detect small perivascular bleeds.
Conclusion
Serial MRI at a field strength of 3 T failed to detect the initial microvascular dysfunction and subsequent small perivascular bleeds in SHRSP; only terminal stages of cerebral microangiopathy were reliably detected. Further investigations at higher magnetic field strengths (7 T) using blood- and flow-sensitive sequences are currently underway.
Background
The effect of smoking on coronary vasomotion has been investigated in the past with various imaging techniques in both short- and long-term smokers. Additionally, coronary vasomotion has been shown to be normalized in long-term smokers by L-Arginine acting as a substrate for NO synthase, revealing the coronary endothelium as the major site of abnormal vasomotor response. Aim of the prospective cohort study was to investigate coronary vasomotion of young healthy short-term smokers via magnetic resonance cold pressor test with and without the administration of L-Arginine and compare obtained results with the ones from nonsmokers.
Methods
Myocardial blood flow (MBF) was quantified with first-pass perfusion MRI on a 1.5 T scanner in healthy short-term smokers (N = 10, age: 25.0 ± 2.8 years, 5.0 ± 2.9 pack years) and nonsmokers (N = 10, age: 34.3 ± 13.6) both at rest and during cold pressor test (CPT). Smokers underwent an additional examination after administration of L-Arginine within a median of 7 days of the naïve examination.
Results
MBF at rest turned out to be 0.77 ± 0.30 (smokers with no L-Arginine; mean ± standard deviation), 0.66 ± 0.21 (smokers L-Arginine) and 0.84 ± 0.08 (nonsmokers). Values under CPT were 1.21 ± 0.42 (smokers no L-Arginine), 1.09 ± 0.35 (smokers L-Arginine) and 1.63 ± 0.33 (nonsmokers). In all groups, MBF was significantly increased under CPT compared to the corresponding rest examination (p < 0.05 in all cases). Additionally, MBF under CPT was significantly different between the smokers and the nonsmokers (p = 0.002). MBF at rest was significantly different between the smokers when L-Arginine was given and the nonsmokers (p = 0.035).
Conclusion
Short-term smokers showed a reduced response to cold both with and without the administration of L-Arginine. However, absolute MBF values under CPT were lower compared to nonsmokers independently of L-Arginine administration.
Even as medical data sets become more publicly accessible, most are restricted to specific medical conditions. Thus, data collection for machine learning approaches remains challenging, and synthetic data augmentation, such as generative adversarial networks (GAN), may overcome this hurdle. In the present quality control study, deep convolutional GAN (DCGAN)-based human brain magnetic resonance (MR) images were validated by blinded radiologists. In total, 96 T1-weighted brain images from 30 healthy individuals and 33 patients with cerebrovascular accident were included. A training data set was generated from the T1-weighted images and DCGAN was applied to generate additional artificial brain images. The likelihood that images were DCGAN-created versus acquired was evaluated by 5 radiologists (2 neuroradiologists [NRs], vs 3 non-neuroradiologists [NNRs]) in a binary fashion to identify real vs created images. Images were selected randomly from the data set (variation of created images, 40%-60%). None of the investigated images was rated as unknown. Of the created images, the NRs rated 45% and 71% as real magnetic resonance imaging images (NNRs, 24%, 40%, and 44%). In contradistinction, 44% and 70% of the real images were rated as generated images by NRs (NNRs, 10%, 17%, and 27%). The accuracy for the NRs was 0.55 and 0.30 (NNRs, 0.83, 0.72, and 0.64). DCGAN-created brain MR images are similar enough to acquired MR images so as to be indistinguishable in some cases. Such an artificial intelligence algorithm may contribute to synthetic data augmentation for "data-hungry" technologies, such as supervised machine learning approaches, in various clinical applications.
Background:
The amount of fatty degeneration (FD) has major impact on the clinical result and cuff integrity after rotator cuff repair. A quantitative analysis with magnet resonance imaging (MRI) spectroscopy was employed to analyze possible correlation of FD with tendon retraction, tendon thickness and patients’ characteristics in full thickness supraspinatus tears.
Methods:
Forty-two patients with full-thickness supraspinatus tears underwent shoulder MRI including an experimental spectroscopic sequence allowing quantification of the fat fraction in the supraspinatus muscle belly. The amount of fatty degeneration was correlated with tendon retraction, tendon thickness, patients’ age, gender, smoker status, symptom duration and body mass index (BMI). Patients were divided in to three groups of retraction (A) 0-10 mm (n=), (B) 11-20 mm (n=) and (C) < 21 mm (n=) and the means of FD for each group were calculated.
Results:
Tendon retraction (R = 0.6) and symptom duration (R = 0.6) correlated positively, whereas tendon thickness correlated negatively (R = − 0.6) with the amount of FD. The fat fraction increased significantly with tendon retraction: Group (A) showed a mean fat mount of 3.7% (±4%), group (B) of 16.7% (±8.2%) and group (C) of 37.5% (±19%). BMI, age and smoker-status only showed weak to moderate correlation with the amount of FD in this cohort.
Conclusion:
MRI spectroscopy revealed significantly higher amount of fat with increasing grade of retraction, symptom duration and decreased tendon thickness. Thus, these parameters may indirectly be associated with the severity of tendon disease.
Fulminant myocarditis is rare but a potentially life-threatening disease. Acute or mild myocarditis following acute ischemia is generally associated with a profound activation of the host’s immune system. On one hand this is mandatory to protect the host’s heart by fighting the invading agents (i.e., bacteria, viruses or other microbial agents) and/or to induce healing and repair processes in the damaged myocardium. On other hand, uncontrolled activation of the immune system may result in the generation of auto-reactive (not always beneficial) immune cells.
Myocarditis or inflammatory cardiomyopathy is characterized by focal or diffuse infiltrates, myocyte necrosis and/or apoptosis and subsequent fibrotic replacement of the heart muscle. In humans, about 30% of the myocarditis-patients develop dilated cardiomyopathy. As the clinical picture of myocarditis is multifaceted, it is difficult to diagnose the disease. Therefore, the main goal of the present work was to test and further develop novel non-invasive methods for the detection of myocardial inflammation by employing both contrast enhanced MRI techniques as well as novel nuclear tracers that are suitable for in vivo PET/ SPECT imaging.
As a part of this thesis, a pre-clinical animal model was successfully established by immunizing female Lewis rats with whole-porcine cardiac myosin (CM). Induction of Experimental Autoimmune Myocarditis (EAM) is considered successful when anti-myosin antibody titers are increased more than 100-fold over control animals and pericardial effusion develops. In addition, cardiac tissues from EAM-rats versus controls were analyzed for the expression of various pro-inflammatory and fibrosis markers. To further exploit non-invasive MRI techniques for the detection of myocarditis, our EAM-rats were injected either with (1) ultra-small Paramagnetic iron oxide particles (USPIO’s; Feraheme®), allowing for in vivo imaging , (2) micron sized paramagnetic iron oxide particles (MPIO) for ex vivo inflammatory cell-tracking by cMRI, or (3) with different radioactive nuclear tracers (67gallium citrate, 68gallium-labeled somatostatin analogue, and 68gallium-labeled cyclic RGD-peptide) which in the present work have been employed for autoradiographic imaging, but in principle are also suitable for in vivo nuclear imaging (PET/SPECT). In order to compare imaging results with histology, consecutive heart sections were stained with hematoxylin & eosin (HE, for cell infiltrates) and Masson Goldner trichrome (MGT, for fibrosis); in addition, immuno-stainings were performed with anti-CD68 (macrophages), anti-SSRT2A (somatostatin receptor type 2A), anti-CD61 (β3-integrins) and anti-CD31 (platelet endothelial cell adhesion molecule 1).
Sera from immunized rats strongly reacted with cardiac myosin. In immunized rats, echocardiography and subsequent MRI revealed huge amounts of pericardial effusion (days 18-21). Analysis of the kinetics of myocardial infiltrates revealed maximal macrophage invasion between days 14 and 28. Disappearance of macrophages resulted in replacement-fibrosis in formerly cell-infiltrated myocardial areas. This finding was confirmed by the time-dependent differential expression of corresponding cytokines in the myocardium. Immunized animals reacted either with an early or a late pattern of post-inflammation fibrosis. Areas with massive cellular infiltrates were easily detectible in autoradiograms showing a high focal uptake of 67gallium-citrate and 68gallium labeled somatostatin analogues (68Ga DOTA-TATE). Myocardium with a loss of cardiomyocytes presented a high uptake of 68gallium labeled cyclic RGD-peptide (68Ga NOTA-RGD). MRI cell tracking experiments with Feraheme® as the contrast-agent were inconclusive; however, strikingly better results were obtained when MPIOs were used as a contrast-agent: histological findings correlated well with in vivo and ex vivo MPIO-enhanced MRI images.
Imaging of myocardial inflammatory processes including the kinetics of macrophage invasion after microbial or ischemic damage is still a major challenge in, both animal models and in human patients. By applying a broad panel of biochemical, histological, molecular and imaging methods, we show here that different patterns of reactivity may occur upon induction of myocarditis using one and the same rat strain. In particular, immunized Lewis rats may react either with an early or a late pattern of macrophage invasion and subsequent post-inflammation fibrosis. Imaging results achieved in the acute inflammatory phase of the myocarditis with MPIOs, 67gallium citrate and 68gallium linked to somatostatin will stimulate further development of contrast agents and radioactive-nuclear tracers for the non-invasive detection of acute myocarditis and in the near future perhaps even in human patients.
Increased aortic stiffness is known to be associated with atherosclerosis and has a predictive value for cardiovascular events. This study aims to investigate the local distribution of early arterial stiffening due to initial atherosclerotic lesions. Therefore, global and local pulse wave velocity (PWV) were measured in ApoE\(^{-/-}\) and wild type (WT) mice using ultrahigh field MRI. For quantification of global aortic stiffness, a new multi-point transit-time (TT) method was implemented and validated to determine the global PWV in the murine aorta. Local aortic stiffness was measured by assessing the local PWV in the upper abdominal aorta, using the flow/area (QA) method. Significant differences between age matched ApoE\(^{-/-}\) and WT mice were determined for global and local PWV measurements (global PWV: ApoE\(^{-/-}\): 2.7 ±0.2m/s vs WT: 2.1±0.2m/s, P<0.03; local PWV: ApoE\(^{-/-}\): 2.9±0.2m/s vs WT: 2.2±0.2m/s, P<0.03). Within the WT mouse group, the global PWV correlated well with the local PWV in the upper abdominal aorta (R\(^2\) = 0.75, P<0.01), implying a widely uniform arterial elasticity.
In ApoE\(^{-/-}\) animals, however, no significant correlation between individual local and global PWV was present (R\(^2\) = 0.07, P = 0.53), implying a heterogeneous distribution of vascular stiffening in early atherosclerosis. The assessment of global PWV using the new multi-point TT measurement technique was validated against a pressure wire measurement in a vessel
phantom and showed excellent agreement. The experimental results demonstrate that vascular stiffening caused by early atherosclerosis is unequally distributed over the length of large vessels. This finding implies that assessing heterogeneity of arterial stiffness by multiple local measurements of PWV might be more sensitive than global PWV to identify early atherosclerotic lesions.
Low field NMR has been successfully used for the evaluation of seed composition and quality, but largely only in crop species. We show here that 1.5T NMR provides a reliable means for analysing the seed lipid fraction present in a wide range of species, where both the seed size and lipid concentration differed by >10 fold. Little use of high field NMR has been made in seed research to date, even though it potentially offers many opportunities for studying seed development, metabolism and storage. Here we demonstrate how 17.5T and 20T NMR can be applied to image seed structure, and analyse lipid and metabolite distribution. We suggest that further technical developments in NMR/MRI will facilitate significant advances in our understanding of seed biology.
The goal of the work presented in this thesis was to explore the possibilities and limitations of MRI / MRS using an ultra high field of 17.6 tesla. A broad range of specific applications and MR methods, from MRI to MRSI and MRS were investigated. The main foci were on sodium magnetic resonance spectroscopic imaging of rodents, magnetic resonance spectroscopy of the mouse brain, and the detection of small amounts of iron labeled stem cells in the rat brain using MRI Sodium spectroscopic imaging was explored since it benefits tremendously from the high magnetic field. Due to the intrinsically low signal in vivo, originating from the low concentrations and short transverse relaxation times, only limited results have been achieved by other researchers until now. Results in the literature include studies conducted on large animals such as dogs to animals as small as rats. No studies performed on mice have been reported, despite the fact that the mouse is the most important laboratory animal due to the ready availability of transgenic strains. Hence, this study concentrated on sodium MRSI of small rodents, mostly mice (brain, heart, and kidney), and in the case of the brain on young rats. The second part of this work concentrated on proton magnetic resonance spectroscopy of the rodent brain. Due to the high magnetic field strength not only the increasing signal but also the extended spectral resolution was advantageous for such kind of studies. The difficulties/limitations of ultra high field MRS were also investigated. In the last part of the presented work detection limits of iron labeled stem cells in vivo using magnetic resonance imaging were explored. The studies provided very useful benchmarks for future researchers in terms of the number of labeled stem cells that are required for high-field MRI studies. Overall this work has shown many of the benefits and the areas that need special attention of ultra high fields in MR. Three topics in MRI, MRS and MRSI were presented in detail. Although there are significant additional difficulties that have to be overcome compared to lower frequencies, none of the work presented here would have been possible at lower field strengths.