Low-energy extracorporeal shockwave therapy (ESWT) improves metaphyseal fracture healing in an osteoporotic rat model.

PURPOSE: As result of the current demographic changes, osteoporosis and osteoporotic fractures are becoming an increasing social and economic burden. In this experimental study, extracorporeal shock wave therapy (ESWT), was evaluated as a treatment option for the improvement of osteoporotic fracture healing. METHODS: A well-established fracture model in the metaphyseal tibia in the osteoporotic rat was used. 132 animals were divided into 11 groups, with 12 animals each, consisting of one sham-operated group and 10 ovariectomized (osteoporotic) groups, of which 9 received ESWT treatment. Different energy flux intensities (0.15 mJ/mm2, 0.35 mJ/mm2, or 0.55 mJ/mm2) as well as different numbers of ESWT applications (once, three times, or five times throughout the 35-day healing period) were applied to the osteoporotic fractures. Fracture healing was investigated quantitatively and qualitatively using micro-CT imaging, quantitative real-time polymerase chain reaction (qRT-PCR) analysis, histomorphometric analysis and biomechanical analysis. RESULTS: The results of this study show a qualitative and quantitative improvement in the osteoporotic fracture healing under low-energy (energy flux intensity: 0,15 mJ/mm2) ESWT and with fewer treatment applications per healing period. CONCLUSION: In conclusion, low-energy ESWT seems to exhibit a beneficial effect on the healing of osteoporotic fractures, leading to improved biomechanical properties, enhanced callus-quantity and -quality, and an increase in the expression of bone specific transcription factors. The results suggest that low-energy ESWT, as main treatment or as adjunctive treatment in addition to a surgical intervention, may prove to be an effective, simple to use, and cost-efficient option for the qualitative and quantitative improvement of osteoporotic fracture healing.

Minimally Invasive Monitoring of Chronic Central Venous Catheter Patency in Mice Using Digital Subtraction Angiography (DSA).

BACKGROUND: Repetitive administration of medication or contrast agents is frequently performed in mice. The introduction of vascular access mini-ports (VAMP) for mice allows long-term vascular catheterization, hereby eliminating the need for repeated vessel puncture. With catheter occlusion being the most commonly reported complication of chronic jugular vein catheterization, we tested whether digital subtraction angiography (DSA) can be utilized to evaluate VAMP patency in mice. METHODS: Twenty-three mice underwent catheterization of the jugular vein and subcutaneous implantation of a VAMP. The VAMP was flushed every second day with 50 µL of heparinized saline solution (25 IU/ml). DSA was performed during injection of 100 µL of an iodine based contrast agent using an industrial X-ray inspection system intraoperatively, as well as 7±2 and 14±2 days post implantation. RESULTS: DSA allowed localization of catheter tip position, to rule out dislocation, kinking or occlusion of a microcatheter, and to evaluate parent vessel patency. In addition, we observed different ante- and retrograde collateral flow patterns in case of jugular vein occlusion. More exactly, 30% of animals showed parent vessel occlusion after 7±2 days in our setting. At this time point, nevertheless, all VAMPs verified intravascular contrast administration. After 14±2 days, intravascular contrast injection was verified in 70% of the implanted VAMPs, whereas at this point of time 5 animals had died or were sacrificed and in 2 mice parent vessel occlusion hampered intravascular contrast injection. Notably, no occlusion of the catheter itself was observed. CONCLUSION: From our observations we conclude DSA to be a fast and valuable minimally invasive tool for investigation of catheter and parent vessel patency and for anatomical studies of collateral blood flow in animals as small as mice.

Implantation of pipeline flow-diverting stents reduces aneurysm inflow without relevantly affecting static intra-aneurysmal pressure.

BACKGROUND: Flow-diverting stent (FDS) implantation is an endovascular treatment option for intracranial aneurysms. However, little is known about the hemodynamic effects. OBJECTIVE: To assess the effect of stent compression on FDS porosity, to evaluate the influence of single and overlapping implantation of FDS on intra-aneurysmal flow profiles, and to correlate stent porosity with changes in static mean intra-aneurysmal pressure. METHODS: Intra-aneurysmal time-density curves were recorded in a pulsatile in vitro flow model before and after implantation of FDSs (Pipeline Embolization Device; ev3) in 7 different types of aneurysm models. Reductions in the maximum contrast inflow and time to maximum intra-aneurysmal contrast were calculated. Micro--computed tomography was performed, and compression-related FDS porosity was measured. The influence of FDS placement on mean static intra-aneurysmal pressure was measured. RESULTS: FDS compression resulted in an almost linear reduction in stent porosity. Stent porosity (struts per 1 mm) correlated significantly with the reduction of aneurysm contrast inflow (R = 0.81, P < .001) and delay until maximum contrast (R = 0.34, P = .001). Circulating intra-aneurysmal high-velocity flow was terminated in all sidewall models after implantation of a single stent. Superimposition of 2 stents reduced maximum intra-aneurysmal contrast by 69.1 ± 3.1% (mean ± SD) in narrow-necked sidewall aneurysm models, whereas no substantial reduction in maximum intra-aneurysmal contrast was observed in wide-necked sidewall aneurysm models. Intra-aneurysmal mean static pressure did not correlate with FDS porosity or number of implanted stents. CONCLUSION: Implantation of FDS effectively reduces aneurysm inflow in a porosity-dependent way without relevantly affecting static mean intra-aneurysmal pressure. ABBREVIATIONS: FDS, flow-diverting stentMAP, mean arterial pressurePED, Pipeline Embolization Device.

Comparison of Fenestra LC, ExiTron nano 6000, and ExiTron nano 12000 for micro-CT imaging of liver and spleen in mice.

RATIONALE AND OBJECTIVES: The purpose of this study was to compare different contrast agents for longitudinal liver and spleen imaging in a mouse model of liver metastasis. MATERIALS AND METHODS: Mice developing liver metastases underwent longitudinal micro-computed tomography imaging after injection of Fenestra LC, ExiTron nano 6000, or ExiTron nano 12000. Elimination times and contrast enhancement of liver and spleen were compared. RESULTS: For all contrast agents, liver contrast peaked at approximately 4 hours and spleen contrast at 48 hours postinjection. A single dose of 100 µL of ExiTron nano 6000 or 12000 resulted in longstanding enhancement of liver and spleen tissue for longer than 3 weeks, whereas repeated injections of 400 µL of Fenestra LC were required to retain contrast at acceptable levels and allowed imaging of the liver/spleen for up to 2 and 9 days, respectively. CONCLUSION: Both ExiTron nano agents provide longer and stronger contrast enhancement of liver and spleen compared to Fenestra LC, and they do so at a 75% lower injection volume in mice.

A Low Cost Metal-Free Vascular Access Mini-Port for Artifact Free Imaging and Repeated Injections in Mice.

PURPOSE: Small injection ports for mice are increasingly used for drug testing or when administering contrast agents. Commercially available mini-ports are expensive single-use items that cause imaging-artifacts. We developed and tested an artifact-free, low-cost, vascular access mini-port (VAMP) for mice. PROCEDURES: Leakage testing of the VAMP was conducted with high speed bolus injections of different contrast agents. VAMP-induced artifacts were assessed using a micro-CT and a small animal MRI (9.4T) scanner ex vivo. Repeated contrast administration was performed in vivo. RESULTS: With the VAMP there was no evidence of leakage with repeated punctures, high speed bolus contrast injections, and drawing of blood samples. In contrast to the tested commercially available ports, the VAMP did not cause artifacts with MRI or CT imaging. CONCLUSIONS: The VAMP is an alternative to commercially available mini-ports and has useful applications in animal research involving imaging procedures and contrast agent testing.

Comparison of digital subtraction angiography, micro-computed tomography angiography and magnetic resonance angiography in the assessment of the cerebrovascular system in live mice.

PURPOSE: Mice are often used as small animal models of brain ischemia, venous thrombosis, or vasospasm. This article aimed at providing an overview of the currently available methodologies for in vivo imaging of the murine cerebrovasculature and comparing the capabilities and limitations of the different methods. METHODS: Micro-computed tomography angiography (CTA) was performed during intra-arterial and intravenous administration of a contrast agent bolus. Digital subtraction angiography (DSA) was performed during intra-arterial administration of contrast agent using the micro-CT scanner. Time-of-flight (ToF) magnetic resonance (MR) angiography was performed using a small animal scanner (9.4 T) equipped with a cryogenic transceive quadrature coil. Datasets were compared for scan time, contrast-to-noise ratio (CNR), temporal and spatial resolution, radiation dose, contrast agent dose and detailed recognition of cerebrovascular structures. RESULTS: Highest spatial resolution was achieved using micro-CTA (16 x 16 x 16 µm) and DSA (14 x 14 µm). Compared to micro-CTA (20-40 s) and ToF-MRA (57 min), DSA provided highest temporal resolutions (30 fps) allowing analyses of the cerebrovascular blood flow. Highest mean CNR was reached using ToF-MRA (50.7 ± 15.0), while CNR of micro-CTA depended on the intra-arterial (19.0 ± 1.0) and intravenous (1.3 ± 0.4) use of agents. The CNR of DSA was 10.0 ± 1.8. CONCLUSIONS: The use of dedicated small animal scanners allows cerebrovascular imaging in live animals as small as mice. As each of the methods analyzed has its advantages and limitations, choosing the best suited imaging modality for a defined question is of great importance. By this means the aforementioned methods offer a great potential for future projects in preclinical cerebrovascular research including ischemic stroke or vasospasm.

Three-dimensional in vivo imaging of the murine liver: a micro-computed tomography-based anatomical study.

Various murine models are currently used to study acute and chronic pathological processes of the liver, and the efficacy of novel therapeutic regimens. The increasing availability of high-resolution small animal imaging modalities presents researchers with the opportunity to precisely identify and describe pathological processes of the liver. To meet the demands, the objective of this study was to provide a three-dimensional illustration of the macroscopic anatomical location of the murine liver lobes and hepatic vessels using small animal imaging modalities. We analysed micro-CT images of the murine liver by integrating additional information from the published literature to develop comprehensive illustrations of the macroscopic anatomical features of the murine liver and hepatic vasculature. As a result, we provide updated three-dimensional illustrations of the macroscopic anatomy of the murine liver and hepatic vessels using micro-CT. The information presented here provides researchers working in the field of experimental liver disease with a comprehensive, easily accessable overview of the macroscopic anatomy of the murine liver.