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ObjectivesMicro-computed tomography (μ-CT) and histology, the current gold standard methods for assessing the formation of new bone and blood vessels, are invasive and/or destructive. With that in mind, a more conservative tool, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), was tested for its accuracy and reproducibility in monitoring neovascularization during bone regeneration. Additionally, the suitability of blood perfusion as a surrogate of the efficacy of osteoplastic materials was evaluated.Materials and methodsSixteen rabbits were used and equally divided into four groups, according to the time of euthanasia (2, 3, 4, and 6 weeks after surgery). The animals were submitted to two 8-mm craniotomies that were filled with blood or autogenous bone. Neovascularization was assessed in vivo through DCE-MRI, and bone regeneration, ex vivo, through μ-CT and histology.ResultsThe defects could be consistently identified, and their blood perfusion measured through DCE-MRI, there being statistically significant differences within the blood clot group between 3 and 6 weeks (p= 0.029), and between the former and autogenous bone at six weeks (p= 0.017). Nonetheless, no significant correlations between DCE-MRI findings on neovascularization and μ-CT (r=−0.101, 95% CI [−0.445; 0.268]) or histology (r= 0.305, 95% CI [−0.133; 0.644]) findings on bone regeneration were observed.ConclusionsThese results support the hypothesis that DCE-MRI can be used to monitor neovascularization but contradict the premise that it could predict bone regeneration as well.

A dedicated, novel, multichannel transmit/receive (Tx/Rx) coil array was designed, simulated, and tested for cardiac magnetic resonance imaging (cMRI) of pigs at 7 T. The cardiac array was composed of 16 elements with physically independent anterior and posterior parts. The array was connected to the MRI scanner in the parallel transmit (pTx) mode forming an 8-channel transmit and 16-channel receive (8Tx/16Rx) coil configuration. The anterior array was composed of four central octagonal elements, which were decoupled using a common central ring (CCR) and shared decoupling capacitors. The surrounding four triangular elements were decoupled from the central four elements using gaps and capacitive decoupling. In total, the eight elements of the anterior array resembled a coil with a symmetrical circular shape. Due to the advantageous arrangement of the elements in conjunction with the novel decoupling method of a CCR, the coupling between the adjacent loop elements was minimized. The posterior array was built using a $4 \times 2$ standard rectangular, symmetric element configuration. The dedicated cardiac array was tested in phantom and in ex vivo MR measurements with a female pig of 46 kg. The dedicated coil array enhanced the signal-to-noise ratio (40 ± 27) in ex vivo measurements of the pig heart by about three times compared to a coil prototype for cardiac human imaging (11.8 ± 7). High-resolution, ex vivo cardiac images were acquired with an in-plane resolution of up to 0.3 mm $\times0.3$ mm using the dedicated pig coil array. The novel cardiac array supports parallel imaging with an acceleration factor (R) of 4 without increasing the mean $g$ -factor within the heart region beyond 1.15.

Introduction Cardiac magnetic resonance (CMR) at ultrahigh field (UHF) offers the potential of high resolution and fast image acquisition. Both technical and physiological challenges associated with CMR at 7T require specific hardware and pulse sequences. This study aimed to assess the current status and existing, publicly available technology regarding the potential of a clinical application of 7T CMR. Methods Using a 7T MRI scanner and a commercially available radiofrequency coil, a total of 84 CMR examinations on 72 healthy volunteers (32 males, age 19–70 years, weight 50–103 kg) were obtained. Both electrocardiographic and acoustic triggering were employed. The data were analyzed regarding the diagnostic image quality and the influence of patient and hardware dependent factors. 50 complete short axis stacks and 35 four chamber CINE views were used for left ventricular (LV) and right ventricular (RV), mono-planar LV function, and RV fractional area change (FAC). Twenty-seven data sets included aortic flow measurements that were used to calculate stroke volumes. Subjective acceptance was obtained from all volunteers with a standardized questionnaire. Results Functional analysis showed good functions of LV (mean EF 56%), RV (mean EF 59%) and RV FAC (mean FAC 52%). Flow measurements showed congruent results with both ECG and ACT triggering. No significant influence of experimental parameters on the image quality of the LV was detected. Small fractions of 5.4% of LV and 2.5% of RV segments showed a non-diagnostic image quality. The nominal flip angle significantly influenced the RV image quality. Conclusion The results demonstrate that already now a commercially available 7T MRI system, without major methods developments, allows for a solid morphological and functional analysis similar to the clinically established CMR routine approach. This opens the door towards combing routine CMR in patients with development of advanced 7T technology.

In this study we aimed to assess the effects of continuous formalin fixation on diffusion and relaxation metrics of the ex vivo porcine heart at 7 T. Magnetic resonance imaging was performed on eight piglet hearts using a 7 T whole body system. Hearts were measured fresh within 3 hours of cardiac arrest followed by immersion in 10% neutral buffered formalin. T\(_{2}\)* and T\(_{2}\) were assessed using a gradient multi‐echo and multi‐echo spin echo sequence, respectively. A spin echo and a custom stimulated echo sequence were employed to assess diffusion time‐dependent changes in metrics of cardiac diffusion tensor imaging. SNR was determined for b = 0 images. Scans were performed for 5 mm thick apical, midcavity and basal slices (in‐plane resolution: 1 mm) and repeated 7, 15, 50, 100 and 200 days postfixation. Eigenvalues of the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) decreased significantly (P < 0.05) following fixation. Relative to fresh hearts, FA values 7 and 200 days postfixation were 90% and 80%, while respective relative ADC values at those fixation stages were 78% and 92%. Statistical helix and sheetlet angle distributions as well as respective mean and median values showed no systematic influence of continuous formalin fixation. Similar to changes in the ADC, values for T\(_{2}\), T\(_{2}\)* and SNR dropped initially postfixation. Respective relative values compared with fresh hearts at day 7 were 64%, 79% and 68%, whereas continuous fixation restored T\(_{2}\), T\(_{2}\)* and SNR leading to relative values of 74%, 100%, and 81% at day 200, respectively. Relaxation parameters and diffusion metrics are significantly altered by continuous formalin fixation. The preservation of microstructure metrics following prolonged fixation is a key finding that may enable future studies of ventricular remodeling in cardiac pathologies.

Purpose MRI of lung airspaces using gases with MR-active nuclei (3He, 129Xe, and 19F) is an important area of research in pulmonary imaging. The volume-controlled administration of gas mixtures is important for obtaining quantitative information from MR images. State-of-the-art gas administration using plastic bags (PBs) does not allow for a precise determination of both the volume and timing of a 3He bolus. Methods A novel application unit (AU) was built according to the requirements of the German medical devices law. Integrated spirometers enable the monitoring of the inhaled gas flow. The device is particularly suited for hyperpolarized (HP) gases (e.g., storage and administration with minimal HP losses). The setup was tested in a clinical trial (n = 10 healthy volunteers) according to the German medicinal products law using static and dynamic ventilation HP-3He MRI. Results The required specifications for the AU were successfully realized. Compared to PB-administration, better reproducibility of gas intrapulmonary distribution was observed when using the AU for both static and dynamic ventilation imaging. Conclusion The new AU meets the special requirements for HP gases, which are storage and administration with minimal losses. Our data suggest that gas AU-administration is superior to manual modes for determining the key parameters of dynamic ventilation measurements. Magn Reson Med 74:884–893, 2015. © 2014 Wiley Periodicals, Inc.

The purpose of this work was to validate ventilation-weighted (VW) and perfusion-weighted (QW) Fourier decomposition (FD) magnetic resonance imaging (MRI) with hyperpolarized (3)He MRI and dynamic contrast-enhanced perfusion (DCE) MRI in a controlled animal experiment. Three healthy pigs were studied on 1.5-T MR scanner. For FD MRI, the VW and QW images were obtained by postprocessing of time-resolved lung image sets. DCE acquisitions were performed immediately after contrast agent injection. (3)He MRI data were acquired following the administration of hyperpolarized helium and nitrogen mixture. After baseline MR scans, pulmonary embolism was artificially produced. FD MRI and DCE MRI perfusion measurements were repeated. Subsequently, atelectasis and air trapping were induced, which followed with FD MRI and (3)He MRI ventilation measurements. Distributions of signal intensities in healthy and pathologic lung tissue were compared by statistical analysis. Images acquired using FD, (3)He, and DCE MRI in all animals before the interventional procedure showed homogeneous ventilation and perfusion. Functional defects were detected by all MRI techniques at identical anatomical locations. Signal intensity in VW and QW images was significantly lower in pathological than in healthy lung parenchyma. The study has shown usefulness of FD MRI as an alternative, noninvasive, and easily implementable technique for the assessment of acute changes in lung function.

High-frequency oscillatory ventilation is looked upon as a lung-protective ventilation strategy. For a further clarification of the physical processes promoting gas transport, a visualization of gas flow and the distribution of ventilation are of considerable interest. Therefore, fluorine-19 magnetic resonance imaging of the imaging gas octafluorocyclobutane (C(4) F(8) ) during high-frequency oscillatory ventilation was performed in five healthy pigs. For that, a mutually compatible ventilation-imaging system was set up and transverse images were acquired every 5 sec using FLASH sequences on a 1.5 T scanner. Despite a drop in signal-to-noise ratio after the onset of high-frequency oscillatory ventilation, for each pig, the four experiments could be analyzed. A mean wash-out time (τ) at 5 Hz of 52.7 ± 18 sec and 125.9 ± 39 sec at 10 Hz, respectively, were found for regions of interest including the whole lung. This is in agreement with the clinical findings, in that wash-out of respiratory gases is significantly prolonged for increased high-frequency oscillatory ventilation frequencies. Our study could be a good starting-point for a further optimization of high-frequency oscillatory ventilation.

PURPOSE: To protect the patient with acute respiratory distress syndrome from ventilator associated lung injury (VALI) high-frequency oscillatory ventilation (HFOV) is used. Clinical experience has proven that HFOV is an efficient therapy when conventional artificial ventilation is insufficient. However, the optimal settings of HFOV parameters, eg, tidal volumes, pressure amplitudes and frequency for maximal lung protection, and efficient gas exchange are not established unambiguously. METHODS: In this work magnetic resonance imaging (MRI) with hyperpolarized (3)He was employed to visualize the redistribution of gas within the cadaver pig lung during HFOV. The saturated slice method was used to characterize fast gas kinetics. RESULTS: The strong differences in kinetics were observed for HFOV-driven gas exchange in comparison with diffusive gas transport (apnea). The significant regional and HFOV frequency dependence was detected for washout and gas exchange within the lungs. Gas redistribution was much faster in posterior than in anterior parts of the lungs during HFOV, in contrast to minor differences with an opposite trend observed in apnea. CONCLUSION: The method shows significant potential for visualization and quantification of gas redistribution under HFOV and may help in optimization of the parameters to improve the clinical effect of HFOV for patients.

The aim of this work was to establish a new, fast, and robust method of flip-angle calibration for magnetic resonance imaging of hyperpolarized 3He. The method called flip-angle measurement with magnetization inversion is based on acquiring images from periodically inverted longitudinal magnetization created using the spatial modulation of magnetization technique. By measuring the width of the area where the magnetization was inverted by the spatial modulation of magnetization preparation in phase images, the flip angle can be generated using a simple equation. To validate and establish the limits of the proposed method, flip-angle measurement with magnetization inversion acquisitions were simulated and applied to proton and hyperpolarized 3He phantoms. Then, the calibration procedure was applied during hyperpolarized 3He magnetic resonance imaging in a healthy volunteer. The advantage of the flip-angle measurement with magnetization inversion method compared with the conventional method based on the assessment of radiofrequency-decay is that it is free of errors induced by relaxation due to oxygen, by imperfect excitation slice profile and by any diffusion of 3He into and out of the slice. Another advantage is that it does not require image processing with external software and therefore can be performed using the implemented tools on the magnetic resonance workstation. Magn Reson Med, 2011. © 2010 Wiley-Liss, Inc.

Purpose Overhauser dynamic nuclear polarization (DNP) allows the production of liquid hyperpolarized substrate inside the MRI magnet bore as well as its administration in continuous flow mode to acquire MR images with enhanced signal-to-noise ratio. We implemented inversion recovery preparation in order to improve contrast-to-noise ratio and to quantify the overall imaging performance of Overhauser DNP-enhanced MRI. Method The negative enhancement created by DNP in combination with inversion recovery (IR) preparation allows canceling selectively the signal originated from Boltzmann magnetization and visualizing only hyperpolarized fluid. The theoretical model describing gain of MR image intensity produced by steady-state continuous flow DNP hyperpolarized magnetization was established and proved experimentally. Results A precise quantification of signal originated purely from DNP hyperpolarization was achieved. A temperature effect on longitudinal relaxation had to be taken into account to fit experimental results with numerical prediction. Conclusion Using properly adjusted IR preparation, the complete zeroing of thermal background magnetization was achieved, providing an essential increase of contrast-to-noise ratio of DNP-hyperpolarized water images. To quantify and optimize the steady-state conditions for MRI with continuous flow DNP, an approach similar to that incorporating transient-state thermal magnetization equilibrium in spoiled fast field echo imaging sequences can be used. Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc.

We present a pilot study based on (19)F-MRI to measure fast and slow wash-in and wash-out kinetics of volatile anesthetics in pig brain.The periodic administration of anesthetics in pulsed mode is used to enhance the sensitivity of the anesthetic concentration detection by (19)F-MRI signal. Temporal correlation analysis allows mapping the kinetics time constants.The clear correlation response to anesthetics concentration changes was found in the brain region in comparison with fatty tissues.The methodology may yield important pharmacological findings on regional effect of the anesthetics in brain and be a step towards human studies.

We have used liquid state (“Overhauser”) Dynamic Nuclear Polarization (DNP) to significantly enhance the signal to noise ratio (SNR) of Magnetic Resonance Imaging (MRI). For the first time this was achieved by hyperpolarizing directly in the MRI-scanner field of 1.5 T in continuous flow mode and immediately delivering the hyperpolarized substance to the imaging site to ensure maximum contrast between hyperpolarized sample and sample at thermal polarization. We achieve a maximum absolute signal enhancement factor of 98; while the hyperpolarized sample is transported at a flow rate of up to 30 ml/h yielding an average flow speed up to 470 mm/s over a distance of approximately 80 mm. A spatial imaging resolution of 100 μm with a signal to noise ratio of 25 was achieved on the flowing sample. Application to MRI contrast enhancement or microfluidic imaging can be envisaged immediately.

In order to better understand the mechanisms of gas transport during High Frequency Oscillatory Ventilation (HFOV) Magnetic Resonance Imaging (MRI) with contrast gases and numerical flow simulations based on Computational Fluid Dynamics(CFD) methods are performed.