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Templates for the acquisition of large datasets such as the Human Connectome Project guide the neuroimaging community to reproducible data acquisition and scientific rigor. By contrast, small animal neuroimaging often relies on laboratory-specific protocols, which limit cross-study comparisons. The establishment of broadly validated protocols may facilitate the acquisition of large datasets, which are essential for uncovering potentially small effects often seen in functional MRI (fMRI) studies. Here, we outline a procedure for the acquisition of fMRI datasets in rats and describe animal handling, MRI sequence parameters, data conversion, preprocessing, quality control and data analysis. The procedure is designed to be generalizable across laboratories, has been validated by using datasets across 20 research centers with different scanners and field strengths ranging from 4.7 to 17.2 T and can be used in studies in which it is useful to compare functional connectivity measures across an extensive range of datasets. The MRI procedure requires 1 h per rat to complete and can be carried out by users with limited expertise in rat handling, MRI and data processing., Competing Interests: Competing interests: C.W. is an employee of Bruker, a manufacturer of preclinical MRI systems., (© 2025. Springer Nature Limited.)

Aims: Mammalian models have been instrumental in investigating adult heart function and human disease. However, electrophysiological differences with human hearts and high costs motivate the need for non-mammalian models. The zebrafish is a well-established genetic model to study cardiovascular development and function; however, analysis of cardiovascular phenotypes in adult specimens is particularly challenging as they are opaque., Methods and Results: Here, we optimized and combined multiple imaging techniques including echocardiography, magnetic resonance imaging, and micro-computed tomography to identify and analyse cardiovascular phenotypes in adult zebrafish. Using alk5a/tgfbr1a mutants as a case study, we observed morphological and functional cardiovascular defects that were undetected with conventional approaches. Correlation analysis of multiple parameters revealed an association between haemodynamic defects and structural alterations of the heart, as observed clinically., Conclusion: We report a new, comprehensive, and sensitive platform to identify otherwise indiscernible cardiovascular phenotypes in adult zebrafish., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Purpose: Segmented echo-planar imaging enables high-resolution diffusion-weighted imaging (DWI). However, phase differences between segments can lead to severe artifacts. This work investigates an algorithm to enable reconstruction of interleaved segmented acquisitions without the need of additional calibration or navigator measurements., Methods: A parallel imaging algorithm is presented that jointly reconstructs all segments of one DWI frame maintaining their phase information. Therefore, the algorithm allows for an iterative improvement of the phase estimates included in the joint reconstruction. Given a limited number of interleaves, the initial-phase estimates can be calculated by a traditional parallel-imaging reconstruction, using the unweighted scan of the DWI measurement as a reference., Results: Reconstruction of phantom data and g-factor simulations show substantial improvement (up to 93% reduction in root mean square error) compared with a generalized auto-calibrating partially parallel-acquisition reconstruction. In vivo experiments show robust reconstruction outcomes in critical imaging situations, including small numbers of receiver channels or low signal-to-noise ratio., Conclusion: An algorithm for the robust reconstruction of segmented DWI data is presented. The method requires neither navigator nor calibration measurements; therefore, it can be applied to existing DWI data sets., (© 2021 International Society for Magnetic Resonance in Medicine.)

In many biomimetic approaches, a deep understanding of the form-structure-function relationships in living and functionally intact organisms, which act as biological role models, is essential. This knowledge is a prerequisite for the identification of parameters that are relevant for the desired technical transfer of working principles. Hence, non-invasive and non-destructive techniques for static (3D) and dynamic (4D) high-resolution plant imaging and analysis on multiple hierarchical levels become increasingly important. In this study we demonstrate that magnetic resonance imaging (MRI) can be used to resolve the plants inner tissue structuring and functioning on the example of four plant concept generators with sizes larger than 5 mm used in current biomimetic research projects: Dragon tree (Dracaena reflexa var. angustifolia), Venus flytrap (Dionaea muscipula), Sugar pine (Pinus lambertiana) and Chinese witch hazel (Hamamelis mollis). Two different MRI sequences were applied for high-resolution 3D imaging of the differing material composition (amount, distribution, and density of various tissues) and condition (hydrated, desiccated, and mechanically stressed) of the four model organisms. Main aim is to better understand their biomechanics, development, and kinematics. The results are used as inspiration for developing novel design and fabrication concepts for bio-inspired technical fiber-reinforced branchings and smart biomimetic actuators., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.)

To date, few optical imaging systems are available in clinical practice to perform noninvasive measurements transcutaneously. Instead, functional imaging is performed using ionizing radiation or intense magnetic fields in most cases. The applicability of fluorescence imaging (e.g., for the detection of fluorescently labeled objects, such as tumors) is limited due to the restricted tissue penetration of light and the required long exposure time. Thus, the development of highly sensitive and easily manageable instruments is necessary to broaden the utility of optical imaging. To advance these developments, an improved fluorescence imaging system was designed in this study that operates on the principle of noncontact laser-induced fluorescence and enables the detection of fluorescence from deeper tissue layers as well as real-time imaging. The high performance of the developed optical laser scanner results from the combination of specific point illumination, an intensified charge-coupled device (ICCD) detector with a novel light trap, and a filtering strategy. The suitability of the laser scanner was demonstrated in two representative applications and an in vivo evaluation. In addition, a comparison with a planar imaging system was performed. The results show that the exposure time with the developed laser scanner can be reduced to a few milliseconds during measurements with a penetration depth of up to 32 mm. Due to these short exposure times, real-time fluorescence imaging can be easily achieved. The ability to measure fluorescence from deep tissue layers enables clinically relevant applications, such as the detection of fluorescently labeled malignant tumors., Competing Interests: We have the following interests. Jens Waldeck is employed by Bruker BioSpin MRI GmbH and Bernhard Müller by ProxiVision GmbH. The Mannheim University of Applied Sciences and ProxiVision GmbH are the inventors of a patent application for the imaging system described, which is not yet assigned a patent number. The patent application name is: “Bildgebendes System zur nichtinvasiven optischen Untersuchung von Gewebe in der Tiefe” There are no further patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

Aim: To determine whether non-steroidal mineralocorticoid receptor (MR) antagonists oppose metabolic syndrome-related end-organ, i.e. cardiac, damage., Materials and Methods: In Zucker fa/fa rats, a rat model of metabolic syndrome, we assessed the effects of the non-steroidal MR antagonist finerenone (oral 2 mg/kg/day) on left ventricular (LV) function, haemodynamics and remodelling (using echocardiography, magnetic resonance imaging and biochemical methods)., Results: Long-term (90 days) finerenone modified neither systolic blood pressure nor heart rate, but reduced LV end-diastolic pressure and LV end-diastolic pressure-volume relationship, without modifying LV end-systolic pressure and LV end-systolic pressure-volume relationship. Simultaneously, long-term finerenone reduced both LV systolic and diastolic diameters, associated with reductions in LV weight and LV collagen density, while proteinuria and renal nGAL expression were reduced. Short-term (7 days) finerenone improved LV haemodynamics and reduced LV systolic diameter, without modifying LV diastolic diameter. Moreover, short-term finerenone increased myocardial tissue perfusion and reduced myocardial reactive oxygen species, while plasma nitrite levels, an indicator of nitric oxide (NO) bio-availability, were increased., Conclusions: In rats with metabolic syndrome, the non-steroidal MR antagonist finerenone opposed metabolic syndrome-related diastolic cardiac dysfunction and nephropathy. This involved acute effects, such as improved myocardial perfusion, reduced oxidative stress/increased NO bioavailability, as well as long-term effects, such as modifications in the myocardial structure., (© 2018 John Wiley & Sons Ltd.)

This study reports preclinical data showing that the interleukin (IL)-1β modulation is a new promising target in the pathophysiological context of heart failure. Indeed, in nondiabetic Wistar and diabetic Goto-Kakizaki rats with chronic heart failure induced by myocardial infarction, administration of the IL-1β antibody gevokizumab improves 'surrogate' markers of survival (i.e., left ventricular remodeling, hemodynamics, and function as well as coronary function). However, whether IL-1β modulation per se or in combination with standard treatments of heart failure improves long-term outcome in human heart failure remains to be determined.

Magnetic Resonance Imaging (MRI) appears as a good surrogate to Computed Tomography (CT) scan as it does not involve radiation. In this context, a 3D anatomical and perfusion MR imaging protocol was developed to follow the evolution of bone regeneration and the neo-vascularization in femoral bone defects in rats. For this, three different biomaterials based on Pullulan-Dextran and containing either Fucoidan or HydroxyApatite or both were implanted. In vivo MRI, ex vivo micro-CT and histology were performed 1, 3 and 5 weeks after implantation. The high spatially resolved (156 × 182 × 195 µm) anatomical images showed a high contrast from the defects filled with biomaterials that decreased over time due to bone formation. The 3D Dynamic Contrast Enhanced (DCE) imaging with high temporal resolution (1 image/19 s) enabled to detect a modification in the Area-Under-The-Gadolinium-Curve over the weeks post implantation. The high sensitivity of MRI enabled to distinguish which biomaterial was the least efficient for bone regeneration, which was confirmed by micro-CT images and by a lower vessel density observed by histology. In conclusion, the methodology developed here highlights the efficiency of longitudinal MRI for tissue engineering as a routine small animal exam.

Purpose: To develop a fast three-dimensional (3D) k-space encoding method based on spiral projection imaging (SPI) with an interleaved golden-angle approach and to validate this novel sequence on small animal models., Methods: A disk-like trajectory, in which each disk contained spirals, was developed. The 3D encoding was performed by tilting the disks with a golden angle. The sharpness was first calculated at different T2* values. Then, the sharpness was measured on phantom using variable undersampling ratios. Finally, the sampling method was validated by whole brain time-of-flight angiography and ultrasmall superparamagnetic iron oxide (USPIO) enhanced free-breathing liver angiography on mouse., Results: The in vitro results demonstrated the robustness of the method for short T2* and high undersampling ratios. In vivo experiments showed the ability to properly detect small vessels in the brain with an acquisition time shorter than 1 min. Free-breathing mice liver angiography showed the insensitivity of this protocol toward motions and flow artifacts, and enabled the visualization of liver motion during breathing., Conclusions: The method implemented here allowed fast 3D k-space sampling with a high undersampling ratio. Combining the advantages of center-out spirals with the flexibility of the golden angle approach could have major implications for real-time imaging. Magn Reson Med 77:1831-1840, 2017. © 2016 International Society for Magnetic Resonance in Medicine., (© 2016 International Society for Magnetic Resonance in Medicine.)

Research in pathologies of the brain, heart and kidney have gained immensely from the plethora of studies that have helped shape new methods in magnetic resonance (MR) for characterizing preclinical disease models. Methodical probing into preclinical animal models by MR is invaluable since it allows a careful interpretation and extrapolation of data derived from these models to human disease. In this review we will focus on the applications of cryogenic radiofrequency (RF) coils in small animal MR as a means of boosting image quality (e.g., by supporting MR microscopy) and making data acquisition more efficient (e.g., by reducing measuring time); both being important constituents for thorough investigational studies on animal models of disease. This review attempts to make the (bio)medical imaging, molecular medicine, and pharmaceutical communities aware of this productive ferment and its outstanding significance for anatomical and functional MR in small rodents. The goal is to inspire a more intense interdisciplinary collaboration across the fields to further advance and progress non-invasive MR methods that ultimately support thorough (patho)physiological characterization of animal disease models. In this review, current and potential future applications for the RF coil technology in cardiovascular, neurovascular, and renal disease will be discussed.

Purpose: Zero echo time (ZTE) imaging with single-pulse excitation is a fast, robust, and silent three-dimensional (3D) method for MRI of short T2 tissues. In this technique, algebraic reconstruction serves to fill gaps in the center of k-space due to finite acquisition dead time. The purpose of this study was to investigate the effect of this operation on depiction characteristics, noise behavior, and achievable bandwidth., Methods: The spatial response function (SRF) and noise covariance resulting from ZTE reconstruction were studied using formal analysis, simulations, and phantom experiments., Results: Three prominent limiting phenomena were identified: SRF behavior within the field of view, heightened sensitivity to out-of-band signal sources, and noise amplification. The related errors all appear as image distortions of low spatial frequency and are strongly attenuated upon the transition from one-dimensional projections to 3D image data. Relying on these observations, ZTE imaging was accomplished with a previously unreached gap size, permitting the depiction of a solid sample with T2 ≈ 25 µs at a bandwidth of 500 kHz., Conclusion: The tightest bandwidth limits in ZTE arise from background signal and radiofrequency (RF) switching transients. Significant advances in ZTE performance will be afforded by faster transmit-receive (T/R) switching with negligible transients and RF coils free of background signal., (© 2014 Wiley Periodicals, Inc.)

Introduction: The purpose of this paper is to develop an easy method to generate both fat signal and banding artifact free 3D balanced Steady State Free Precession (bSSFP) images at high magnetic field., Methods: In order to suppress fat signal and bSSFP banding artifacts, two or four images were acquired with the excitation frequency of the water-selective binomial radiofrequency pulse set On Resonance or shifted by a maximum of 3/4TR. Mice and human volunteers were imaged at 7 T and 3 T, respectively to perform whole-body and musculoskeletal imaging. "Sum-Of-Square" reconstruction was performed and combined or not with parallel imaging., Results: The frequency selectivity of 1-2-3-2-1 or 1-3-3-1 binomial pulses was preserved after (3/4TR) frequency shifting. Consequently, whole body small animal 3D imaging was performed at 7 T and enabled visualization of small structures within adipose tissue like lymph nodes. In parallel, this method allowed 3D musculoskeletal imaging in humans with high spatial resolution at 3 T. The combination with parallel imaging allowed the acquisition of knee images with ~500 μm resolution images in less than 2 min. In addition, ankles, full head coverage and legs of volunteers were imaged, demonstrating the possible application of the method also for large FOV., Conclusion: In conclusion, this robust method can be applied in small animals and humans at high magnetic fields. The high SNR and tissue contrast obtained in short acquisition times allows to prescribe bSSFP sequence for several preclinical and clinical applications.

Background: Enhanced heart rate observed in metabolic syndrome (MS) contributes to the deterioration of left ventricular (LV) function via impaired LV filling and relaxation, increased myocardial O2 consumption, and reduced coronary perfusion. However, whether heart rate reduction (HRR) opposes LV dysfunction observed in MS is unknown., Methods: We assessed in Zucker fa/fa rats, a rat model of MS, the cardiovascular effects of HRR induced by the If current inhibitor S38844 (3 mg · kg(-1) · d(-1))., Results: Delayed short-term (4 days) and long-term (90 days) HRR induced by S38844 reduced LV end-diastolic pressure and LV end-diastolic pressure-volume relation, increased myocardial tissue perfusion, decreased myocardial oxidized glutathione levels, and preserved cardiac output, without modifying LV end-systolic pressure and LV end-systolic pressure-volume relation, although only long-term S38844 opposed LV collagen accumulation. Long-term S38844 improved flow-induced endothelium-dependent dilatation of mesenteric arteries, while metabolic parameters, such as plasma glucose levels, and Hb1c, were never modified., Conclusions: In rats with MS, HRR induced by the If inhibitor S38844 improved LV diastolic function and endothelium-dependent vascular dilatation, independent from modifications in metabolic status. Moreover, this improvement in cardiac function involves not only immediate effects such as improved myocardial perfusion and reduced oxidative stress but also long-term effects such as modifications in the myocardial structure.

Purpose: Zero echo time (ZTE) imaging is a fast, robust, and silent three-dimensional technique for direct MRI of tissues with rapid transverse relaxation. It is conventionally performed with hard, block-shaped excitation pulses short enough to excite spins uniformly over a large bandwidth. With this approach, the achievable flip angle (FA) is limited by the available B1 amplitude. The purpose of this work is to accomplish ZTE imaging with larger FAs by combined amplitude and frequency modulation of the excitation pulse while keeping the pulse duration short enough to limit acquisition dead time., Methods: Quantitative performance criteria for FA yield and uniformity of radio frequency (RF) pulses were developed and used to optimize hyperbolic secant pulse shapes. The RF pulses were implemented on a 4.7 T animal MRI system, included in algebraic image reconstruction, and tested in experiments on phantoms and tissue samples., Results: The optimized modulated pulses provide considerably improved performance with respect to uniformity and mean FA as compared with block-shaped counterparts of the same maximum length. Using these pulses, ZTE images of excellent uniformity were obtained with enhanced FA and thus expanded contrast versatility., Conclusion: The performance of ZTE imaging can be significantly improved by employing optimized short amplitude- and frequency-modulated RF pulses., (© 2014 Wiley Periodicals, Inc.)

Purpose: Magnetic particle imaging (MPI) is a new radiologic imaging modality. For the first time, a commercial preclinical scanner is installed. The goal of this study was to establish a workflow between MPI and magnetic resonance imaging (MRI) scanners for a complete in vivo examination of a mouse and to generate the first co-registered in vivo MR-MP images., Materials and Methods: The in vivo examination of five mice were performed on a preclinical MPI scanner and a 7 Tesla preclinical MRI system. MRI measurements were used for anatomical referencing and validation of the injection of superparamagnetic iron oxide (SPIO) particles during a dynamic MPI scan. We extracted MPI data of the injection phase and co-registered it with MRI data., Results: A workflow process for a combined in vivo MRI and MPI examination was established. A successful injection of ferucarbotran was proven in MPI and MRI. MR-MPI co-registration allocated the SPIOs in the inferior vena cava and the heart during and shortly after the injection., Conclusion: The acquisition of preclinical MPI and MRI data is feasible and allows the combined analysis of MR-MPI information., (© Georg Thieme Verlag KG Stuttgart · New York.)

This work describes the first experimental realization of three-dimensional spatially selective excitation using parallel transmission in vivo. For the design of three-dimensional parallel excitation pulses with short durations and high excitation accuracy, the choice of a suitable transmit k-space trajectory is crucial. For this reason, the characteristics of a stack-of-spirals trajectory and of a concentric-shells trajectory were examined in an initial simulation study. It showed that, especially when undersampling the trajectories in combination with parallel transmission, experimental parameters such as transmit-coil geometry and off-resonance conditions have an essential impact on the suitability of the selected trajectory and undersampling scheme. Both trajectories were applied in MR inner-volume imaging experiments which demonstrate that acceptably short and robust three-dimensional selective pulses can be achieved if the trajectory is temporally optimized and its actual path is measured and considered during pulse calculation. Pulse durations as short as 3.2 ms were realized and such pulses were appropriate to accurately excite arbitrarily shaped volumes in a corn cob and in a rat in vivo. Reduced field-of-view imaging of these selectively excited targets allowed high spatial resolution and significantly reduced measurement times and furthermore demonstrates the feasibility of three-dimensional parallel excitation in realistic MRI applications in vivo., (Copyright © 2012 Wiley Periodicals, Inc.)

Multidimensional spatially selective excitation (SSE) has stimulated a variety of useful applications in magnetic resonance imaging and magnetic resonance spectroscopy, which have regained considerable interest after the recent introduction of parallel excitation. For SSE, radiofrequency pulses are designed specifically for certain time-courses of spatially encoding magnetic fields (SEM) which are applied simultaneously with the radiofrequency pulses. However, experimental imperfections of gradient-systems and undesired SEM field contributions often prevent the correct co-action of radiofrequency pulses and gradient-waveforms and therefore degrade the fidelity of excitation patterns, especially for parallel excitation. To cope with such imperfections, a classical measurement of k-space-trajectories can be performed followed by an adaptation of the SSE-pulses. However, this method is limited to linear SEM field distributions, which are describable in the k-space-formalism. Hence, this work presents a more sophisticated method consisting in a spatially resolved measurement of the temporal phase evolution of the transverse magnetization. This exhaustive phase information can be incorporated into pulse-design algorithms to compensate even for undesired spatially nonlinear, dynamic SEM field contributions. Both approaches are assessed in various experimental scenarios and individual benefits and limitations are discussed. The adaptation of SSE-pulses to experimentally achieved calibration data turned out to be very beneficial, and especially the novel spatially resolved method exhibited high potential for robust SSE even in adverse experimental setups., (Copyright © 2010 Wiley-Liss, Inc.)