Cardiac-respiratory self-gated cine ultra-short echo time (UTE) cardiovascular magnetic resonance for assessment of functional cardiac parameters at high magnetic fields

Background: To overcome flow and electrocardiogram-trigger artifacts in cardiovascular magnetic resonance (CMR), we have implemented a cardiac and respiratory self-gated cine ultra-short echo time (UTE) sequence. We have assessed its performance in healthy mice by comparing the results with those obtained with a self-gated cine fast low angle shot (FLASH) sequence and with echocardiography. Methods: 2D self-gated cine UTE (TE/TR = 314 μs/6.2 ms, resolution: 129 × 129 μm, scan time per slice: 5 min 5 sec) and self-gated cine FLASH (TE/TR = 3 ms/6.2 ms, resolution: 129 × 129 μm, scan time per slice: 4 min 49 sec) images were acquired at 9.4 T. Volume of the left and right ventricular (LV, RV) myocardium as well as the end-diastolic and -systolic volume was segmented manually in MR images and myocardial mass, stroke volume (SV), ejection fraction (EF) and cardiac output (CO) were determined. Statistical differences were analyzed by using Student t test and Bland-Altman analyses. Results: Self-gated cine UTE provided high quality images with high contrast-to-noise ratio (CNR) also for the RV myocardium (CNRblood-myocardium = 25.5 ± 7.8). Compared to cine FLASH, susceptibility, motion, and flow artifacts were considerably reduced due to the short TE of 314 μs. The aortic valve was clearly discernible over the entire cardiac cycle. Myocardial mass, SV, EF and CO determined by self-gated UTE were identical to the values measured with self-gated FLASH and showed good agreement to the results obtained by echocardiography. Conclusions: Self-gated UTE allows for robust measurement of cardiac parameters of diagnostic interest. Image quality is superior to self-gated FLASH, rendering the method a powerful alternative for the assessment of cardiac function at high magnetic fields.</p

MRI visualization of Staphyloccocus aureus-induced infective endocarditis in mice

Infective endocarditis (IE) is a severe and often fatal disease, lacking a fast and reliable diagnostic procedure. The purpose of this study was to establish a mouse model of Staphylococcus aureus-induced IE and to develop a MRI technology to characterize and diagnose IE. To establish the mouse model of hematogenous IE, aortic valve damage was induced by placing a permanent catheter into right carotid artery. 24 h after surgery, mice were injected intravenously with either iron particle-labeled or unlabeled S. aureus (strain 6850). To distinguish the effect of IE from mere tissue injury or recruited macrophages, subgroups of mice received sham surgery prior to infection (n = 17), received surgery without infection (n = 8), or obtained additionally injection of free iron particles to label macrophages (n = 17). Cardiac MRI was performed 48 h after surgery using a self-gated ultra-short echo time (UTE) sequence (TR/TE, 5/0.31 ms; in-plane/slice, 0.125/1 mm; duration, 12:08 min) to obtain high-resolution, artifact-free cinematographic images of the valves. After MRI, valves were either homogenized and plated on blood agar plates for determination of bacterial titers, or sectioned and stained for histology. In the animal model, both severity of the disease and mortality increased with bacterial numbers. Infection with 105 S. aureus bacteria reliably caused endocarditis with vegetations on the valves. Cinematographic UTE MRI visualised the aortic valve over the cardiac cycle and allowed for detection of bacterial vegetations, while mere tissue trauma or labeled macrophages were not detected. Iron labeling of S. aureus was not required for detection. MRI results were consistent with histology and microbial assessment. These data showed that S. aureus-induced IE in mice can be detected by MRI. The established mouse model allows for investigation of the pathophysiology of IE, testing of novel drugs and may serve for the development of a clinical diagnostic strategy

Bacteria tracking by in vivo magnetic resonance imaging

Background: Different non-invasive real-time imaging techniques have been developed over the last decades to study bacterial pathogenic mechanisms in mouse models by following infections over a time course. In vivo investigations of bacterial infections previously relied mostly on bioluminescence imaging (BLI), which is able to localize metabolically active bacteria, but provides no data on the status of the involved organs in the infected host organism. In this study we established an in vivo imaging platform by magnetic resonance imaging (MRI) for tracking bacteria in mouse models of infection to study infection biology of clinically relevant bacteria. Results: We have developed a method to label Gram-positive and Gram-negative bacteria with iron oxide nano particles and detected and pursued these with MRI. The key step for successful labeling was to manipulate the bacterial surface charge by producing electro-competent cells enabling charge interactions between the iron particles and the cell wall. Different particle sizes and coatings were tested for their ability to attach to the cell wall and possible labeling mechanisms were elaborated by comparing Gram-positive and -negative bacterial characteristics. With 5-nm citrate-coated particles an iron load of 0.015 ± 0.002 pg Fe/bacterial cell was achieved for Staphylococcus aureus. In both a subcutaneous and a systemic infection model induced by iron-labeled S. aureus bacteria, high resolution MR images allowed for bacterial tracking and provided information on the morphology of organs and the inflammatory response. Conclusion: Labeled with iron oxide particles, in vivo detection of small S. aureus colonies in infection models is feasible by MRI and provides a versatile tool to follow bacterial infections in vivo. The established cell labeling strategy can easily be transferred to other bacterial species and thus provides a conceptual advance in the field of molecular MRI.<br

Renal Allograft Rejection: Noninvasive Ultrasound- and MRI-Based Diagnostics

To date, allogeneic kidney transplantation remains the best available therapeutic option for patients with end-stage renal disease regarding overall survival and quality of life. Despite the advancements in immunosuppressive drugs and protocols, episodes of acute allograft rejection, a sterile inflammatory process, continue to endanger allograft survival. Since effective treatment for acute rejection episodes is available, instant diagnosis of this potentially reversible graft injury is imperative. Although histological examination by invasive core needle biopsy of the graft remains the gold standard for the diagnosis of ongoing rejection, it is always associated with the risk of causing substantial graft injury as a result of the biopsy procedure itself. At the same time, biopsies are not immediately feasible for a considerable number of patients taking anticoagulants due to the high risk of complications such as bleeding and uneven distribution of pathological changes within the graft. This can result in the wrong diagnosis due to the small size of the tissue sample taken. Therefore, there is a need for a tool that overcomes these problems by being noninvasive and capable of assessing the whole organ at the same time for specific and fast detection of acute allograft rejection. In this article, we review current state-of-the-art approaches for noninvasive diagnostics of acute renal transplant inflammation, i.e., rejection. We especially focus on nonradiation-based methods using magnetic resonance imaging (MRI) and ultrasound

Functional imaging of murine hearts using accelerated self-gated UTE cine MRI

We introduce a fast protocol for ultra-short echo time (UTE) Cine magnetic resonance imaging (MRI) of the beating murine heart. The sequence involves a self-gated UTE with golden-angle radial acquisition and compressed sensing reconstruction. The self-gated acquisition is performed asynchronously with the heartbeat, resulting in a randomly undersampled kt-space that facilitates compressed sensing reconstruction. The sequence was tested in 4 healthy rats and 4 rats with chronic myocardial infarction, approximately 2 months after surgery. As a control, a non-accelerated self-gated multi-slice FLASH sequence with an echo time (TE) of 2.76 ms, 4.5 signal averages, a matrix of 192 × 192, and an acquisition time of 2 min 34 s per slice was used to obtain Cine MRI with 15 frames per heartbeat. Non-accelerated UTE MRI was performed with TE = 0.29 ms, a reconstruction matrix of 192 × 192, and an acquisition time of 3 min 47 s per slice for 3.5 averages. Accelerated imaging with 2×, 4× and 5× undersampled kt-space data was performed with 1 min, 30 and 15 s acquisitions, respectively. UTE Cine images up to 5× undersampled kt-space data could be successfully reconstructed using a compressed sensing algorithm. In contrast to the FLASH Cine images, flow artifacts in the UTE images were nearly absent due to the short echo time, simplifying segmentation of the left ventricular (LV) lumen. LV functional parameters derived from the control and the accelerated Cine movies were statistically identical. Keywords: Compressed sensing; UTE; Cardiac MRI; Functional imagin

Velocity mapping of the aortic flow at 9.4 T in healthy mice and mice with induced heart failure using time-resolved three-dimensional phase-contrast MRI (4D PC MRI)

\u3cp\u3eObjectives: In this study, we established and validated a time-resolved three-dimensional phase-contrast magnetic resonance imaging method (4D PC MRI) on a 9.4 T small-animal MRI system. Herein we present the feasibility of 4D PC MRI in terms of qualitative and quantitative flow pattern analysis in mice with transverse aortic constriction (TAC). Materials and methods: 4D PC FLASH images of a flow phantom and mouse heart were acquired at 9.4 T using a four-point phase-encoding scheme. The method was compared with slice-selective PC FLASH and ultrasound using Bland–Altman analysis. Advanced 3D streamlines were visualized utilizing Voreen volume-rendering software. Results: In vitro, 4D PC MRI flow profiles showed the transition between laminar and turbulent flow with increasing velocities. In vivo, 4D PC MRI data of the ascending aorta and the pulmonary artery were confirmed by ultrasound, resulting in linear regressions of R\u3csup\u3e2\u3c/sup\u3e &gt; 0.93. Magnitude- and direction-encoded streamlines differed substantially pre- and post-TAC surgery. Conclusions: 4D PC MRI is a feasible tool for in vivo velocity measurements on high-field small-animal scanners. Similar to clinical measurement, this method provides a complete spatially and temporally resolved dataset of the murine cardiovascular blood flow and allows for three-dimensional flow pattern analysis.\u3c/p\u3

A novel MRI compatible mouse fracture model to characterize and monitor bone regeneration and tissue composition

Over the last years, murine in vivo magnetic resonance imaging (MRI) contributed to a new understanding of tissue composition, regeneration and diseases. Due to artefacts generated by the currently used metal implants, MRI is limited in fracture healing research so far. In this study, we investigated a novel MRI-compatible, ceramic intramedullary fracture implant during bone regeneration in mice. Three-point-bending revealed a higher stiffness of the ceramic material compared to the metal implants. Electron microscopy displayed a rough surface of the ceramic implant that was comparable to standard metal devices and allowed cell attachment and growth of osteoblastic cells. MicroCT-imaging illustrated the development of the callus around the fracture site indicating a regular progressing healing process when using the novel implant. In MRI, different callus tissues and the implant could clearly be distinguished from each other without any artefacts. Monitoring fracture healing using MRI-compatible implants will improve our knowledge of callus tissue regeneration by 3D insights longitudinal in the same living organism, which might also help to reduce the consumption of animals for future fracture healing studies, significantly. Finally, this study may be translated into clinical application to improve our knowledge about human bone regeneration