Paul Borm

Dual contrast agent for computed tomography and magnetic resonance hard tissue imaging.

Calcium phosphate cements (CPCs) are commonly used bone substitute materials, which closely resemble the composition of the mineral phase of bone. However, this high similarity to natural bone also results in difficult discrimination from the bone tissue by common imaging modalities, that is, plain X-ray radiography and three-dimensional computed tomography (CT). In addition, new imaging techniques introduced for bone tissue visualization, like magnetic resonance imaging (MRI), face a similar problem. Even at high MRI resolution, the lack of contrast between CPCs and surrounding bone is evident. Therefore, this study aimed to evaluate the feasibility of a dual contrast agent, traceable with both CT and MRI as enhancers of CPC/bone tissue contrast. Our formulation is based on the use of silica beads as vectors, which encapsulate and carry contrast-enhancing nanoparticles, in our case, colloidal Gold and Superparamagnetic Iron oxide particles (SPIO). The bead suspension was incorporated within a calcium phosphate powder. The resultant cements were then tested both in vitro and in vivo in a femoral condyle defect model in rats. Results showed that the mechanical properties of the cement were not significantly affected by the inclusion of the beads. Both in vitro and in vivo data proved the homogeneous incorporation of the contrast within the cement and its visual localization, characterized by a short-term CT contrast enhancement and a long-term MR effect recognizable by the characteristic blooming shape. Finally, no signs of adverse tissue reactions were noticed in vivo. In conclusion, this study proved the feasibility of a multimodal contrast agent as an inert and biocompatible enhancer of CaP cement versus bone tissue contrast.

A theranostic agent to enhance osteogenic and magnetic resonance imaging properties of calcium phosphate cements.

With biomimetic biomaterials, like calcium phosphate cements (CPCs), non-invasive assessment of tissue regeneration is challenging. This study describes a theranostic agent (TA) to simultaneously enhance both imaging and osteogenic properties of such a bone substitute material. For this purpose, mesoporous silica beads were produced containing an iron oxide core to enhance bone magnetic resonance (MR) contrast. The same beads were functionalized with silane linkers to immobilize the osteoinductive protein BMP-2, and finally received a calcium phosphate coating, before being embedded in the CPC. Both in vitro and in vivo tests were performed. In vitro testing showed that the TA beads did not interfere with essential material properties like cement setting. Furthermore, bioactive BMP-2 could be efficiently released from the carrier-beads. In vivo testing in a femoral condyle defect rat model showed long-term MR contrast enhancement, as well as improved osteogenic capacity. Moreover, the TA was released during CPC degradation and was not incorporated into the newly formed bone. In conclusion, the described TA was shown to be suitable for longitudinal material degradation and bone healing studies.

Magnetic Particle Imaging: A Resovist Based Marking Technology for Guide Wires and Catheters for Vascular Interventions

Magnetic Particle Imaging (MPI) is able to provide high temporal and good spatial resolution, high signal to noise ratio and sensitivity. Furthermore, it is a truly quantitative method as its signal strength is proportional to the concentration of its tracer, superparamagnetic iron oxide nanoparticles (SPIOs), over a wide range practically relevant concentrations. Thus, MPI is proposed as a promising future method for guidance of vascular interventions. To implement this, devices such as guide wires and catheters have to be discernible in MPI, which can be achieved by coating already commercially available devices with SPIOs. In this proof of principle study the feasibility of that approach is demonstrated. First, a Ferucarbotran-based SPIO-varnish was developed by embedding Ferucarbotran into an organic based solvent. Subsequently, the biocompatible varnish was applied to a commercially available guidewire and diagnostic catheter for vascular interventional purposes. In an interventional setting using a vessel phantom, the coating proved to be mechanically and chemically stable and thin enough to ensure normal handling as with uncoated devices. The devices were visualized in 3D on a preclinical MPI demonstrator using a system function based image reconstruction process. The system function was acquired with a probe of the dried varnish prior to the measurements. The devices were visualized with a very hightemporal resolution and a simple catheter/guide wire maneuver was demonstrated.Magnetic particle imaging (MPI) is able to provide high temporal and good spatial resolution, high signal to noise ratio and sensitivity. Furthermore, it is a truly quantitative method as its signal strength is proportional to the concentration of its tracer, superparamagnetic iron oxide nanoparticles (SPIOs), over a wide range practically relevant concentrations. Thus, MPI is proposed as a promising future method for guidance of vascular interventions. To implement this, devices such as guide wires and catheters have to be discernible in MPI, which can be achieved by coating already commercially available devices with SPIOs. In this proof of principle study the feasibility of that approach is demonstrated. First, a Ferucarbotran-based SPIO-varnish was developed by embedding Ferucarbotran into an organic based solvent. Subsequently, the biocompatible varnish was applied to a commercially available guidewire and diagnostic catheter for vascular interventional purposes. In an interventional setting using a vessel phantom, the coating proved to be mechanically and chemically stable and thin enough to ensure normal handling as with uncoated devices. The devices were visualized in 3D on a preclinical MPI demonstrator using a system function based image reconstruction process. The system function was acquired with a probe of the dried varnish prior to the measurements. The devices were visualized with a very high temporal resolution and a simple catheter/guide wire maneuver was demonstrated.

Labeling of Collagen Type I Templates with a Naturally Derived Contrast Agent for Noninvasive MR Imaging in Soft Tissue Engineering

In vivo monitoring of tissue-engineered constructs is important to assess their integrity, remodeling, and degradation. However, this is challenging when the contrast with neighboring tissues is low, necessitating labeling with contrast agents (CAs), but current CAs have limitations (i.e., toxicity, negative contrast, label instability, and/or inappropriate size). Therefore, a naturally derived hemin-L-lysine (HL) complex is used as a potential CA to label collagen-based templates for magnetic resonance imaging (MRI). Labeling does not change the basic characteristics of the collagen templates. When hybrid templates composed of collagen type I reinforced with degradable polymers are subcutaneously implanted in mice, longitudinal visualization by MRI is possible with good contrast and in correlation with template remodeling. In contrast, unlabeled collagen templates are hardly detectable and the fate of these templates cannot be monitored by MRI. Interestingly, tissue remodeling and vascularization are enhanced within HL-labeled templates. Thus, HL labeling is presented as a promising universal imaging marker to label tissue-engineered implants for MRI, which additionally seems to accelerate tissue regeneration.

The depiction of labeled guidewires in a phantom in an interventional MRI setting

The aim of this study was to evaluate the influence of bandwidth and echotime on the size of signal voids created by iron oxide nanoparticles on a guidewire.