Ioana Slabu

In vivo MRI visualization of mesh shrinkage using surgical implants loaded with superparamagnetic iron oxides.

BackgroundProsthetic mesh implants are widely used in hernia surgery. To show long-term mesh-related complications such as shrinkage or adhesions, a precise visualization of meshes and their vicinity in vivo is important. By supplementing mesh fibers with ferro particles, magnetic resonance imaging (MRI) can help to delineate the mesh itself. This study aimed to demonstrate and quantify time-dependent mesh shrinkage in vivo by MRI.MethodsPolyvinylidenfluoride (PVDF) meshes with incorporated superparamagnetic iron oxides (SPIOs) were implanted as an abdominal wall replacement in 30 rats. On days 1, 7, 14, or 21, MRI was performed using a gradient echo sequence with repetition time (TR)/echo time (TE) of 50/4.6 and a flip angle of 20°. The length, width, and area of the device were measured on axial, coronal, and sagittal images, and geometric deformations were assessed by surgical explantation.ResultsIn all cases, the meshes were visualized and their area estimated by measuring the length and width of the mesh. The MRI presented a mean area shrinkage in vivo of 13% on day 7, 23% on day 14, and 23% on day 21. Postmortem measurements differed statistically from MRI, with a mean area shrinkage of 23% on day 7, 28% on day 14, and 30% on day 21. Ex vivo measurements of shrinkage showed in vivo measurements to be overestimated approximately 8%. Delineation of the mesh helped to show folding or adhesions close to the intestine.ConclusionLoading of surgical meshes with SPIOs allows their precise visualization during MRI and guarantees an accurate in vivo assessment of their shrinkage. The authors’ observation clearly indicates that shrinkage in vivo is remarkably less than that shown by illustrated explantation measurements. The use of MRI with such meshes could be a reliable technique for checking on proper operation of implanted meshes and showing related complications, obviating the need for exploratory open surgical revision.

A Concept for Magnetic Resonance Visualization of Surgical Textile Implants

Purpose:To develop a method for visualizing surgical textile implant (STI) with superparamagnetic iron oxides (SPIO), using magnetic resonance imaging (MRI). Therefore, positive-contrast inversion-recovery with on-resonant water suppression (IRON) was applied and its properties were evaluated in vitro. Materials and Methods:STI with different concentrations of SPIO integrated into the base material were produced. Imaging was performed on a clinical 1.5 Tesla scanner, using conventional balanced gradient echo sequences (SSFP), T2*-weighted sequences, and IRON-imaging. In vitro experiments were conducted in an agarose phantom. On MR-images, contrast-to-noise-ratios, and the dimensions of the implant were assessed. Results:Conventional MRI exhibited SPIO-loaded STI as signal voids. Using IRON, the mesh was clearly exhibited hyperintensely with suppression of on-resonant background signals with a distinct differentiation to other sources of off-resonances. Concentrations of approximately 9 mg/g led to best positive contrast and highest contrast-to-noise-ratios using IRON. Depending on B0-orientation, phase encoding direction and the STIs SPIO-load, the IRON-signal showed a characteristic pattern and an overestimation of STI size up to 4.6 mm. Conclusion:The integration of SPIOs into the base material combined with IRON is a feasible approach to visualize STI with MRI. This method could help to identify mesh-related problems in time and to reduce the need for surgical revision.

Fluorescent magnetoliposomes as a platform technology for functional and molecular MR and optical imaging

Here, we present a detailed characterisation of rhodamine B-containing magnetoliposomes (FLU-ML), emphasising the dependence of their fluorescence properties on the presence of iron oxide cores, and the molar fraction of the fluorophore. The magnetoliposome types used exist as colloidally stable, negatively charged clusters with an average hydrodynamic diameter of 95 nm. The molar rhodamine B fractions were 0.67 % and 1.97 %. Rhodamine B normalised fluorescence, quantum yields and fluorescence lifetimes were substantially reduced by inner filter effects as the magnetoliposome concentration is increased, by increasing molar rhodamine B fraction, and by quenching originating from the iron oxide cores. MR relaxometry at 3 T revealed extremely high r2 relaxivities (440 to 554 s-1mM-1) and moderately high r1 values (2.06 to 3.59 s-1mM-1). Upon incubating human prostate carcinoma (PC-3) cells with FLU-ML, a dose-dependent particle internalisation was found by MR relaxometry. In addition, the internalised FLU-ML were clearly visible by fluorescence microscopy. At the FLU-ML concentrations used (up to 3 × 10³ M Fe) cell viability was not substantially impaired. These results provide valuable insights on the fluorescence properties of bimodal magnetoliposomes and open promising perspectives for the use of these materials as a platform technology for advanced functional and molecular MR and optical imaging applications.

Mapping of proton relaxation near superparamagnetic iron oxide particle-loaded polymer threads for magnetic susceptibility difference quantification.

ObjectivesConventional radiological methods, including magnetic resonance imaging (MRI), fail to visualize polymeric surgical mesh implants because of small thread dimensions and material characteristics. For MRI delineation of such meshes, superparamagnetic iron oxide particles (SPIOs) are integrated in the mesh polymer. Usually, if SPIOs are used as an intravenous contrast agent, they increase the R1 and R2 of adjacent protons. It can be assumed that embedding SPIOs in polymers alters their molecular dynamics. The aim of this study was to investigate the influence of SPIO integration in polymer on the relaxation of adjacent protons. Materials and MethodsPolymer threads were placed in an agarose phantom. At 1.5 T, R1, R2, and R2* maps were calculated from multi inversion-recovery spin echo, multi–spin echo, and multi–gradient echo images, respectively. The threads were aligned parallel or orthogonal to B0. ResultsNo impact of SPIO on proton R1 and R2 was observed. R2* was increased by the SPIO-loaded threads. R1 and R2 amplitude maps showed a magnetic susceptibility difference of 0.97 ppm/(mg SPIO/g polymer) around SPIO-loaded threads. ConclusionsIn contrast to SPIO in aqueous solutions, polymer-embedded SPIO do not affect proton R1 and R2. However, embedded SPIO generate strong local static magnetic field gradients. Thus, SPIO integration is suitable to control the magnetic susceptibility of polymer threads. This can be exploited to visualize implanted polymer-based meshes in MRI using R2* susceptible sequences. Because no impact on R1 and R2 of adjacent protons by SPIO embedded in mesh threads was observed, structures adjacent to implanted meshes will be observable in R1 and R2 maps.

Optimization of magnetic drug targeting by mathematical modeling and simulation of magnetic fields

Magnetic drug targeting is a method of transporting drugs to specific locations within the human body. For this purpose superparamagnetic nanoparticles (MNP) are combined with chemotherapeutic agents, injected into the circulatory system and guided to a target site using an external magnetic field that acts on the MNP.

Agglomeration of magnetic nanoparticles and its effects on magnetic hyperthermia

Abstract Magnetic fluid hyperthermia (MFH) is a promising approach for organ-confined tumor treatment. In MFH, magnetic nanoparticles (MNP) are magnetically targeted at the tumor site and heated in an alternating magnetic field. The heat produced by the MNP is used to cause tumor cell death. At the tumor site, MNP bind to the cell membrane and form agglomerates before they are internalized into the intracellular compartments. Intracellular immobilization and the formation of agglomerates influence heating properties of MNP making it difficult to control the local heating inside the tumor. In this study, we investigated MNP agglomerated samples for their heating efficiency. We found an increase in heating of 22 % upon agglomeration. If MNP are additionally immobilized, however, the heating decreases by 30 %. Consequently, due to the binding of bigger MNP agglomerates at cellular level, heating efficiency inside tumors is assumed to decrease.

Combining Bulk Temperature and Nanoheating Enables Advanced Magnetic Fluid Hyperthermia Efficacy on Pancreatic Tumor Cells

Many efforts are made worldwide to establish magnetic fluid hyperthermia (MFH) as a treatment for organ-confined tumors. However, translation to clinical application hardly succeeds as it still lacks of understanding the mechanisms determining MFH cytotoxic effects. Here, we investigate the intracellular MFH efficacy with respect to different parameters and assess the intracellular cytotoxic effects in detail. For this, MiaPaCa-2 human pancreatic tumor cells and L929 murine fibroblasts were loaded with iron-oxide magnetic nanoparticles (MNP) and exposed to MFH for either 30 min or 90 min. The resulting cytotoxic effects were assessed via clonogenic assay. Our results demonstrate that cell damage depends not only on the obvious parameters bulk temperature and duration of treatment, but most importantly on cell type and thermal energy deposited per cell during MFH treatment. Tumor cell death of 95% was achieved by depositing an intracellular total thermal energy with about 50% margin to damage of healthy cells. This is attributed to combined intracellular nanoheating and extracellular bulk heating. Tumor cell damage of up to 86% was observed for MFH treatment without perceptible bulk temperature rise. Effective heating decreased by up to 65% after MNP were internalized inside cells.

Establishment of a biophysical model to optimize endoscopic targeting of magnetic nanoparticles for cancer treatment

Superparamagnetic iron oxide nanoparticles (SPION) may be used for local tumor treatment by coupling them to a drug and accumulating them locally with magnetic field traps, that is, a combination of permanent magnets and coils. Thereafter, an alternating magnetic field generates heat which may be used to release the thermosensitively bound drug and for hyperthermia. Until today, only superficial tumors can be treated with this method. Our aim was to transfer this method into an endoscopic setting to also reach the majority of tumors located inside the body. To find the ideal endoscopic magnetic field trap, which accumulates the most SPION, we first developed a biophysical model considering anatomical as well as physical conditions. Entities of choice were esophageal and prostate cancer. The magnetic susceptibilities of different porcine and rat tissues were measured with a superconducting quantum interference device. All tissues showed diamagnetic behavior. The evaluation of clinical data (computed tomography scan, endosonography, surgical reports, pathological evaluation) of patients gave insight into the topographical relationship between the tumor and its surroundings. Both were used to establish the biophysical model of the tumors and their surroundings, closely mirroring the clinical situation, in which we could virtually design, place and evaluate different electromagnetic coil configurations to find optimized magnetic field traps for each tumor entity. By simulation, we could show that the efficiency of the magnetic field traps can be enhanced by 38-fold for prostate and 8-fold for esophageal cancer. Therefore, our approach of endoscopic targeting is an improvement of the magnetic drug-targeting setups for SPION tumor therapy as it holds the possibility of reaching tumors inside the body in a minimal-invasive way. Future animal experiments must prove these findings in vivo.

Simulation of Magnetic Nanoparticles in Blood Flow for Magnetic Drug Targeting Applications.

A new magnetic drug targeting model of placing an array of permanent magnets and coils inside hollow organs of the body was developed. This gives the possibility to target e. g. prostate carcinoma, oesophagus adenocarcinoma or bile duct Klatskin tumours with drugs bounded to magnetic nanoparticles. The targeting model uses FEM based simulations and describes the interaction of an external magnetic field with single suspended superparamagnetic iron oxide (SPIO) nanoparticles in blood flow, thereby, quantifying the amount of the accumulated SPIO at a vessel wall.

Behavior of Superparamagnetic Iron Oxides in Magnetic Targeting Models

In order to improve the specificity of chemotherapeutic drugs towards pathological tissue, we investigated minimally invasive delivery methods by simulation of a magnetic targeting system. This system aims at the concentration of superparamagnetic nanoparticles at a tumor site in the body under the influence of external magnetic forces after injection of the particles into the circulatory system. Therefore, the properties of differently synthesized superparamagnetic iron oxides (SPIOs) were analyzed and implemented in a simulation model. FEM simulations were performed using the Navier-Stokes equation of fluid motion, which describes the hydrodynamic forces that act on the SPIOs in blood flow, with an additional magnetic term caused by the interaction between the SPIOs and the external magnetic field. As a result, we could show the feasibility of magnetic targeting by combining the optimization of both the magnetic fields and the SPIOs’ properties.