Effects of image homogeneity on stenosis visualization at 7 T in a coronary artery phantom study: With and without B1-shimming and parallel transmission.

BACKGROUND: To investigate the effects of B1-shimming and radiofrequency (RF) parallel transmission (pTX) on the visualization and quantification of the degree of stenosis in a coronary artery phantom using 7 Tesla (7 T) magnetic resonance imaging (MRI). METHODS: Stenosis phantoms with different grades of stenosis (0%, 20%, 40%, 60%, 80%, and 100%; 5 mm inner vessel diameter) were produced using 3D printing (clear resin). Phantoms were imaged with four different concentrations of diluted Gd-DOTA representing established arterial concentrations after intravenous injection in humans. Samples were centrally positioned in a thorax phantom of 30 cm diameter filled with a custom-made liquid featuring dielectric properties of muscle tissue. MRI was performed on a 7 T whole-body system. 2D-gradient-echo sequences were acquired with an 8-channel transmit 16-channel receive (8 Tx / 16 Rx) cardiac array prototype coil with and without pTX mode. Measurements were compared to those obtained with identical scan parameters using a commercially available 1 Tx / 16 Rx single transmit coil (sTX). To assess reproducibility, measurements (n = 15) were repeated at different horizontal angles with respect to the B0-field. RESULTS: B1-shimming and pTX markedly improved flip angle homogeneity across the thorax phantom yielding a distinctly increased signal-to-noise ratio (SNR) averaged over a whole slice relative to non-manipulated RF fields. Images without B1-shimming showed shading artifacts due to local B1+-field inhomogeneities, which hampered stenosis quantification in severe cases. In contrast, B1-shimming and pTX provided superior image homogeneity. Compared with a conventional sTX coil higher grade stenoses (60% and 80%) were graded significantly (p<0.01) more precise. Mild to moderate grade stenoses did not show significant differences. Overall, SNR was distinctly higher with B1-shimming and pTX than with the conventional sTX coil (inside the stenosis phantoms 14%, outside the phantoms 32%). Both full and half concentration (10.2 mM and 5.1 mM) of a conventional Gd-DOTA dose for humans were equally suitable for stenosis evaluation in this phantom study. CONCLUSIONS: B1-shimming and pTX at 7 T can distinctly improve image homogeneity and therefore provide considerably more accurate MR image analysis, which is beneficial for imaging of small vessel structures.

Less than 9.5-mm coracohumeral distance on axial magnetic resonance imaging scans predicts for subscapularis tear.

BACKGROUND: Diagnosis of subscapularis (SSC) tendon lesions on magnetic resonance imaging (MRI) can be challenging. A small coracohumeral distance (CHD) has been associated with SSC tears. This study was designed to define a specific threshold value for CHD to predict SSC tears on axial MRI scans. METHODS: This retrospective study included 172 shoulders of 168 patients who underwent arthroscopic surgery for rotator cuff tear or glenohumeral instability. Diagnostic arthroscopy confirmed an SSC tear in 62 cases (36.0%, test group a), rotator cuff tear tears other than SSC in 71 cases (41.3%, control group b) and glenohumeral instability without any rotator cuff tear in 39 cases (22.7%, zero-sample group c). All patients had a preoperative MRI of the shoulder (1.5T or 3T). Minimum CHD was measured on axial fat-suppressed proton density-, T2-, or T1-weigthed sequences. Receiver operating characteristics analysis was used to determine the threshold value for CHD, and sensitivity and specificity were calculated. RESULTS: CHD measurement had a good interobserver reliability (Intraclass correlation coefficient 0.799). Mean CHD was highly significantly (P < .001) less for test group a (mean 7.3 mm, standard deviation ± 2.2) compared with control group b (mean 11.1 mm, standard deviation ± 2.3) or zero-sample group c (mean 13.6 mm, standard deviation ± 2.9). A threshold value of CHD <9.5 mm had a sensitivity of 83.6% and a specificity of 83.9% to predict SSC tears. CONCLUSION: A CHD <9.5 mm on MRI is predictive of SSC lesions and a valuable tool to diagnose SSC tears.

Near real-time magnetic particle imaging for visual assessment of vascular stenosis in a phantom model.

PURPOSE: This study aimed to investigate the potential of magnetic particle imaging (MPI) to quantify artificial stenoses in vessel phantoms in near real-time. METHODS: Custom-made stenosis phantoms with different degrees of stenosis (0%, 25%, 50%, 75%, and 100%; length 40 mm, inner diameter 8 mm, Polyoxymethylene) were filled with diluted Ferucarbotran (superparamagnetic iron-oxide nanoparticle (SPION) tracer agent, 500 mmol (Fe)/l). A traveling wave MPI scanner (spatial resolution ~ 2 mm, gradient strength ~ 1.5 T/m, field of view: 65 mm length and 29 mm diameter, frequencies f1 = 1050 Hz and f2 = 12150 Hz) was used to acquire images of the phantoms (200 ms total acquisition time per image, 10 averages). Standardized grey scaling was used for comparability. All measured stenoses (n = 80) were graded manually using a dedicated software tool. RESULTS: MPI allowed for accurate visualization of stenoses at a frame rate of 5frames per second. Less severe stenoses were detected more precisely than higher-grade stenoses and came with smaller standard deviations. In particular, the 0%, 25%, 50%, 75%, and 100% stenosis phantom were measured as 3.7 ± 2.7% (mean ± standarddeviation), 18.6 ± 1.8%, 52.8 ± 3.7%, 77.8 ± 14.8% and 100 ± 0%. Geometrical distortions occurred around the center of the high-grade stenosis and led to higher standard deviations compared to lower grade stenoses. In the frame of this study the MPI signal depended linearly on the SPION concentration down to 0.05 mmol (Fe)/l. CONCLUSION: Near real-time MPI accurately visualized and quantified different stenosis grades in vascular phantoms.

B0 shimming of the human heart at 7T.

PURPOSE: Inhomogeneities of the static magnetic B0 field are a major limiting factor in cardiac MRI at ultrahigh field (≥ 7T), as they result in signal loss and image distortions. Different magnetic susceptibilities of the myocardium and surrounding tissue in combination with cardiac motion lead to strong spatio-temporal B0 -field inhomogeneities, and their homogenization (B0 shimming) is a prerequisite. Limitations of state-of-the-art shimming are described, regional B0 variations are measured, and a methodology for spherical harmonics shimming of the B0 field within the human myocardium is proposed. METHODS: The spatial B0 -field distribution in the heart was analyzed as well as temporal B0 -field variations in the myocardium over the cardiac cycle. Different shim region-of-interest selections were compared, and hardware limitations of spherical harmonics B0 shimming were evaluated by calibration-based B0 -field modeling. The role of third-order spherical harmonics terms was analyzed as well as potential benefits from cardiac phase-specific shimming. RESULTS: The strongest B0 -field inhomogeneities were observed in localized spots within the left-ventricular and right-ventricular myocardium and varied between systolic and diastolic cardiac phases. An anatomy-driven shim region-of-interest selection allowed for improved B0 -field homogeneity compared with a standard shim region-of-interest cuboid. Third-order spherical harmonics terms were demonstrated to be beneficial for shimming of these myocardial B0 -field inhomogeneities. Initial results from the in vivo implementation of a potential shim strategy were obtained. Simulated cardiac phase-specific shimming was performed, and a shim term-by-term analysis revealed periodic variations of required currents. CONCLUSION: Challenges in state-of-the-art B0 shimming of the human heart at 7 T were described. Cardiac phase-specific shimming strategies were found to be superior to vendor-supplied shimming.

3D cone-beam CT with a twin robotic x-ray system in elbow imaging: comparison of image quality to high-resolution multidetector CT.

BACKGROUND: Elbow imaging is challenging with conventional multidetector computed tomography (MDCT), while cone-beam CT (CBCT) provides superior options. We compared intra-individually CBCT versus MDCT image quality in cadaveric elbows. METHODS: A twin robotic x-ray system with new CBCT mode and a high-resolution clinical MDCT were compared in 16 cadaveric elbows. Both systems were operated with a dedicated low-dose (LD) protocol (equivalent volume CT dose index [CTDIvol(16 cm)] = 3.3 mGy) and a regular clinical scan dose (RD) protocol (CTDIvol(16 cm) = 13.8 mGy). Image quality was evaluated by two radiologists (R1 and R2) on a seven-point Likert scale, and estimation of signal intensity in cancellous bone was conducted. Wilcoxon signed-rank tests and intraclass correlation coefficient (ICC) statistics were used. RESULTS: The CBCT prototype provided superior subjective image quality compared to MDCT scans (for RD, p ≤ 0.004; for LD, p ≤ 0.001). Image quality was rated very good or excellent in 100% of the cases by both readers for RD CBCT, 100% (R1) and 93.8% (R2) for LD CBCT, 62.6% and 43.8% for RD MDCT, and 0.0% and 0.0% for LD MDCT. Single-measure ICC was 0.95 (95% confidence interval 0.91-0.97; p < 0.001). Software-based assessment supported subjective findings with less "undecided" pixels in CBCT than dose-equivalent MDCT (p < 0.001). No significant difference was found between LD CBCT and RD MDCT. CONCLUSIONS: In cadaveric elbow studies, the tested cone-beam CT prototype delivered superior image quality compared to high-end multidetector CT and showed a potential for considerable dose reduction.

Parallel magnetic particle imaging.

Magnetic Particle Imaging (MPI) is a promising tomographic method to visualize the distribution of superparamagnetic materials in three-dimensions. For encoding, a strong gradient represented by a field free point (FFP) or a field free line (FFL) is steered rapidly through the field of view (FOV), acquiring the signal successively. Conventional MPI scanners only provide a single FFP or FFL to sample the entire scan volume, which limits the size of the FOV and/or the temporal resolution. The alternative scanner concept of Traveling Wave MPI (TWMPI) uses a dynamic linear gradient array (dLGA) for dynamic FFP generation along the symmetry axis. The TWMPI scanner is capable of creating multiple FFPs simultaneously, and usually care is taken to locate only a single FFP in the desired FOV. In this manuscript, the concept of parallel MPI utilizing multiple FFPs simultaneously is introduced. For that, conceptual simulations are presented followed by reconstruction approaches for visualization of parallel MPI signals. In addition, an initial parallel MPI experiment with simultaneous acquisition of signals from two FFPs inside the FOV of the same scanner using two receive chains is demonstrated. This allows scanning a doubled FOV within the same acquisition time without sacrificing resolution compared to the standard TWMPI scanner.

Superspeed Bolus Visualization for Vascular Magnetic Particle Imaging.

Magnetic Particle Imaging (MPI) is a fast imaging technique to visualize the distribution of superparamagnetic iron-oxide nanoparticles (SPIONs). For spatial encoding, a field free area is moved rapidly through the field of view (FOV) generating localized signal. Fast moving samples, e.g., a bolus of SPIONs traveling through the large veins in the human body carried by blood flow with velocities in the order of ~45 cm/s, cause temporal blurring in MPI measurements using common sequences and reconstruction techniques. This hampers the evaluation of dynamics of fast moving samples. In this manuscript, a first study on fast moving samples visualized within an MPI scanner is demonstrated. By optimizing parameters for imaging and reconstruction, the dynamics of a fast moving bolus at different velocities can be visualized with high temporal resolution without blurring artifacts.

Magnetic Particle Imaging meets Computed Tomography: first simultaneous imaging.

Magnetic Particle Imaging (MPI) is a promising new tomographic modality for fast as well as three-dimensional visualization of magnetic material. For anatomical or structural information an additional imaging modality such as computed tomography (CT) is required. In this paper, the first hybrid MPI-CT scanner for multimodal imaging providing simultaneous data acquisition is presented.

Magnetic Particle Imaging-Guided Stenting.

Purpose:To assess the feasibility of magnetic particle imaging (MPI) to guide stenting in a phantom model. Materials and Methods: MPI is a new tomographic imaging method based on the background-free magnetic field detection of a tracer agent composed of superparamagnetic iron oxide nanoparticles (SPIOs). All experiments were conducted on a custom-built MPI scanner (field of view: 29-mm diameter, 65-mm length; isotropic spatial resolution 1-1.5-mm). Stenosis phantoms (n=3) consisted of polyvinyl chloride (PVC) tubes (8-mm inner diameter) prepared with centrally aligned cable binders to form a ~50% stenosis. A dedicated image reconstruction algorithm allowed precise tracking of endovascular instruments at 8 frames/s with a latency time of ~115 ms. A custom-made MPI-visible lacquer was used to manually label conventional guidewires, balloon catheters, and stainless steel balloon-expandable stents. Vascular stenoses were visualized by injecting a diluted SPIO tracer (ferucarbotran, 10 mmol iron/L) into the vessel phantoms. Balloon angioplasty and stent placement were performed by inflating balloon catheters and stent delivery balloons with diluted ferucarbotran. Results: After deployment of the stent, the markers on its ends were clearly visible. The applied lacquer markers were thin enough to not relevantly alter gliding properties of the devices while withstanding friction during the experiments. Placing an optimized flexible lacquer formulation on the preexisting radiopaque stent markers provided enough stability to withstand stent expansion. Final MPA confirmed successful stenosis treatment, facilitated by the disappearance of the lacquer markers on the stent due to differences in SPIO concentration. Thus, the in-stent lumen could be visualized without interference by the signal from the markers. Conclusion: Near real-time visualization of MPI-guided stenting of stenoses in a phantom model is feasible. Optimized MPI-visible markers can withstand the expansion process of stents.

Magnetic Particle Imaging Guided Real-Time Percutaneous Transluminal Angioplasty in a Phantom Model.

PURPOSE: To investigate the potential of real-time magnetic particle imaging (MPI) to guide percutaneous transluminal angioplasty (PTA) of vascular stenoses in a phantom model. MATERIALS AND METHODS: Experiments were conducted on a custom-built MPI scanner. Vascular stenosis phantoms consisted of polyvinyl chloride tubes (inner diameter 8 mm) prepared with a centrally aligned cable tie to form ~ 50% stenoses. MPI angiography for visualization of stenoses was performed using the superparamagnetic iron oxide nanoparticle-based contrast agent Ferucarbotran (10 mmol (Fe)/l). Balloon catheters and guidewires for PTA were visualized using custom-made lacquer markers based on Ferucarbotran. Stenosis dilation (n = 3) was performed by manually inflating the PTA balloon with diluted Ferucarbotran. An online reconstruction framework was implemented for real-time imaging with very short latency time. RESULTS: Visualization of stenosis phantoms and guidance of interventional instruments in real-time (4 frames/s, ~ 100 ms latency time) was possible using an online reconstruction algorithm. Labeling of guidewires and balloon catheters allowed for precise visualization of instrument positions. CONCLUSION: Real-time MPI-guided PTA in a phantom model is feasible.

Assessment of local pulse wave velocity distribution in mice using k-t BLAST PC-CMR with semi-automatic area segmentation.

BACKGROUND: Local aortic pulse wave velocity (PWV) is a measure for vascular stiffness and has a predictive value for cardiovascular events. Ultra high field CMR scanners allow the quantification of local PWV in mice, however these systems are yet unable to monitor the distribution of local elasticities. METHODS: In the present study we provide a new accelerated method to quantify local aortic PWV in mice with phase-contrast cardiovascular magnetic resonance imaging (PC-CMR) at 17.6 T. Based on a k-t BLAST (Broad-use Linear Acquisition Speed-up Technique) undersampling scheme, total measurement time could be reduced by a factor of 6. The fast data acquisition enables to quantify the local PWV at several locations along the aortic blood vessel based on the evaluation of local temporal changes in blood flow and vessel cross sectional area. To speed up post processing and to eliminate operator bias, we introduce a new semi-automatic segmentation algorithm to quantify cross-sectional areas of the aortic vessel. The new methods were applied in 10 eight-month-old mice (4 C57BL/6J-mice and 6 ApoE (-/-)-mice) at 12 adjacent locations along the abdominal aorta. RESULTS: Accelerated data acquisition and semi-automatic post-processing delivered reliable measures for the local PWV, similiar to those obtained with full data sampling and manual segmentation. No statistically significant differences of the mean values could be detected for the different measurement approaches. Mean PWV values were elevated for the ApoE (-/-)-group compared to the C57BL/6J-group (3.5 ± 0.7 m/s vs. 2.2 ± 0.4 m/s, p < 0.01). A more heterogeneous PWV-distribution in the ApoE (-/-)-animals could be observed compared to the C57BL/6J-mice, representing the local character of lesion development in atherosclerosis. CONCLUSION: In the present work, we showed that k-t BLAST PC-MRI enables the measurement of the local PWV distribution in the mouse aorta. The semi-automatic segmentation method based on PC-CMR data allowed rapid determination of local PWV. The findings of this study demonstrate the ability of the proposed methods to non-invasively quantify the spatial variations in local PWV along the aorta of ApoE (-/-)-mice as a relevant model of atherosclerosis.

Contrast-enhanced voiding urosonography phantom study: intravenous iodinated and gadolinium-based contrast agents may cause false-negative results in assessment of vesicoureteral reflux in children.

BACKGROUND: Contrast-enhanced voiding urosonography (ce-VUS) is commonly requested simultaneously to other diagnostic imaging necessitating intravenous contrast agents. To date there is limited knowldedge about intravesical interactions between different types of contrast agents. OBJECTIVE: To assess the effect of excreted intravenous iodinated and gadolinium-based contrast agents on the intravesical distribution of ultrasound contrast within contrast-enhanced voiding urosonography. MATERIALS AND METHODS: Iodinated (iomeprol, iopamidol) and gadolinium-based (gadoterate meglumine) contrast agents were diluted to bladder concentration and injected into balloons filled with saline solution. CT scans were performed to assess the contrast distribution in these phantoms. Regions of interest were placed at the top and bottom side of each balloon and Hounsfield units (HU) were measured. Three other balloons were filled with saline solution and contrast media likewise. The ultrasound contrast agent sulphur hexafluoride was added and its distribution was assessed using sonography. RESULTS: MDCT scans showed a separation of two liquid layers in all bladder phantoms with the contrast layers located at the bottom and the saline solution at the top. Significant differences of the HU measurements at the top and bottom side were observed (P < 0.001-0.007). Following injection of ultrasound contrast agent, US showed its distribution exclusively among the saline solution. CONCLUSIONS: False-negative results of contrast-enhanced voiding urosonography may occur if it is performed shortly after imaging procedures requiring intravenous contrast.

Production of recombinant antigens and antibodies in Nicotiana benthamiana using 'magnifection' technology: GMP-compliant facilities for small- and large-scale manufacturing.

This review describes the adaptation of the plant virus-based transient expression system, magnICON(®) for the at-scale manufacturing of pharmaceutical proteins. The system utilizes so-called "deconstructed" viral vectors that rely on Agrobacterium-mediated systemic delivery into the plant cells for recombinant protein production. The system is also suitable for production of hetero-oligomeric proteins like immunoglobulins. By taking advantage of well established R&D tools for optimizing the expression of protein of interest using this system, product concepts can reach the manufacturing stage in highly competitive time periods. At the manufacturing stage, the system offers many remarkable features including rapid production cycles, high product yield, virtually unlimited scale-up potential, and flexibility for different manufacturing schemes. The magnICON system has been successfully adaptated to very different logistical manufacturing formats: (1) speedy production of multiple small batches of individualized pharmaceuticals proteins (e.g. antigens comprising individualized vaccines to treat NonHodgkin's Lymphoma patients) and (2) large-scale production of other pharmaceutical proteins such as therapeutic antibodies. General descriptions of the prototype GMP-compliant manufacturing processes and facilities for the product formats that are in preclinical and clinical testing are provided.

Development of novel types of plastid transformation vectors and evaluation of factors controlling expression.

Two new vector types for plastid transformation were developed and uidA reporter gene expression was compared to standard transformation vectors. The first vector type does not contain any plastid promoter, instead it relies on extension of existing plastid operons and was therefore named "operon-extension" vector. When a strongly expressed plastid operon like psbA was extended by the reporter gene with this vector type, the expression level was superior to that of a standard vector under control of the 16S rRNA promoter. Different insertion sites, promoters and 5'-UTRs were analysed for their effect on reporter gene expression with standard and operon-extension vectors. The 5'-UTR of phage 7 gene 10 in combination with a modified N-terminus was found to yield the highest expression levels. Expression levels were also strongly dependent on external factors like plant or leaf age or light intensity. In the second vector type, named "split" plastid transformation vector, modules of the expression cassette were distributed on two separate vectors. Upon co-transformation of plastids with these vectors, the complete expression cassette became inserted into the plastome. This result can be explained by successive co-integration of the split vectors and final loop-out recombination of the duplicated sequences. The split vector concept was validated with different vector pairs.

A tomato enzyme catalyzing the phosphorylation of 3,4-dihydroxy-2-butanone.

A riboflavin biosynthesis ribB mutant of Escherichia coli deficient of 3,4-dihydroxy-2-butanone 4-phosphate synthase was complemented with a cDNA library from Lycopersicon esculentum. The complementing gene was isolated and expressed in E. coli. The resulting protein was shown to specify a 62 kDa protein which phosphorylates dihydroxyacetone, both enantiomers of 3,4-dihydroxy-2-butanone, and several other aldoses and ketoses. Sequence analysis revealed homology to dihydroacetone kinases (dak) genes from plants, animals, fungi and some eubacteria. Genes with similarity to the 5' part of the dak gene from tomato were found in many other eubacteria. The physiological role of the dak gene is still incompletely known.