Mariana Gueorguieva

Hybrid gold-iron oxide nanoparticles as a multifunctional platform for biomedical application

BackgroundIron oxide nanoparticles (IONPs) have increasing applications in biomedicine, however fears over long term stability of polymer coated particles have arisen. Gold coating IONPs results in particles of increased stability and robustness. The unique properties of both the iron oxide (magnetic) and gold (surface plasmon resonance) result in a multimodal platform for use as MRI contrast agents and as a nano-heater.ResultsHere we synthesize IONPs of core diameter 30 nm and gold coat using the seeding method with a poly(ethylenimine) intermediate layer. The final particles were coated in poly(ethylene glycol) to ensure biocompatibility and increase retention times in vivo. The particle coating was monitored using FTIR, PCS, UV–vis absorption, TEM, and EDX. The particles appeared to have little cytotoxic effect when incubated with A375M cells. The resultant hybrid nanoparticles (HNPs) possessed a maximal absorbance at 600 nm. After laser irradiation in agar phantom a ΔT of 32°C was achieved after only 90 s exposure (50 μgmL-1). The HNPs appeared to decrease T2 values in line with previously clinically used MRI contrast agent Feridex®.ConclusionsThe data highlights the potential of these HNPs as dual function MRI contrast agents and nano-heaters for therapies such as cellular hyperthermia or thermo-responsive drug delivery.

Image-based 3D modeling and validation of radiofrequency interstitial tumor ablation using a tissue-mimicking breast phantom

PurposeMinimally invasive treatment of solid cancers, especially in the breast and liver, remains clinically challenging, despite a variety of treatment modalities, including radiofrequency ablation (RFA), microwave ablation or high-intensity focused ultrasound. Each treatment modality has advantages and disadvantages, but all are limited by placement of a probe or US beam in the target tissue for tumor ablation and monitoring. The placement is difficult when the tumor is surrounded by large blood vessels or organs. Patient-specific image-based 3D modeling for thermal ablation simulation was developed to optimize treatment protocols that improve treatment efficacy.MethodsA tissue-mimicking breast gel phantom was used to develop an image-based 3D computer-aided design (CAD) model for the evaluation of a planned RF ablation. First, the tissue-mimicking gel was cast in a breast mold to create a 3D breast phantom, which contained a simulated solid tumor. Second, the phantom was imaged in a medical MRI scanner using a standard breast imaging MR sequence. Third, the MR images were converted into a 3D CAD model using commercial software (ScanIP, Simpleware), which was input into another commercial package (COMSOL Multiphysics) for RFA simulation and treatment planning using a finite element method (FEM). For validation of the model, the breast phantom was experimentally ablated using a commercial (RITA) RFA electrode and a bipolar needle with an electrosurgical generator (DRE ASG-300). The RFA results obtained by pre-treatment simulation were compared with actual experimental ablation.ResultsA 3D CAD model, created from MR images of the complex breast phantom, was successfully integrated with an RFA electrode to perform FEM ablation simulation. The ablation volumes achieved both in the FEM simulation and the experimental test were equivalent, indicating that patient-specific models can be implemented for pre-treatment planning of solid tumor ablation.ConclusionA tissue-mimicking breast gel phantom and its MR images were used to perform FEM 3D modeling and validation by experimental thermal ablation of the tumor. Similar patient-specific models can be created from preoperative images and used to perform finite element analysis to plan radiofrequency ablation. Clinically, the method can be implemented for pre-treatment planning to predict the effect of an individual’s tissue environment on the ablation process, and this may improve the therapeutic efficacy.

Liver displacement during ventilation in Thiel embalmed human cadavers - a possible model for research and training in minimally invasive therapies

Abstract Respiration-related movement of organs is a complication in a range of diagnostic and interventional procedures. The development and validation of techniques to compensate for such movement requires appropriate models. Human cadavers embalmed with the Thiel method remain flexible and could provide a suitable model. In this study liver displacement during ventilation was assessed in eight Thiel embalmed cadavers, all of which showed thoracic and abdominal motion. Four cadavers displayed realistic lung behaviour, one showed some signs of pneumothorax after prolonged ventilation, one had limited filling of the lungs, and two displayed significant leakage of air into the thorax. A coronal slice containing the largest section through the liver was imaged with a real-time Fast Gradient Echo (FGR) MRI sequence: Craniocaudal displacement of the liver was then determined from a time-series of slices. The maximum liver displacement observed in the cadavers ranged from 7 to 35 mm. The ventilation applied was comparable to tidal breathing at rest and the results found for liver displacement are similar to values in the literature for respiratory motion of the liver under similar conditions. This indicates that Thiel embalmed cadavers have potential as a model for research and training in minimally invasive procedures.

Effect of the hybrid composition on the physicochemical properties and morphology of iron oxide–gold nanoparticles

Hybrid nanoparticles (HNPs) formed from iron oxide cores and gold nano-shells are becoming increasingly applicable in biomedicine. However, little investigation has been carried out on the effects of the constituent components on their physical characteristics. Here we determine the effect of polymer intermediate, gold nano-shell thickness and magnetic iron oxide core diameter on the morphological and physical properties of these nano-hybrids. Our findings suggest that the use of polymer intermediate directly impacts the morphology of the nanostructure formed. Here, we observed the formation of nano-sphere and nano-star structures by varying the cationic polymer intermediate. The nano-stars formed have a larger magnetic coercivity, T2 relaxivity and exhibited a unique characteristic nano-heating pattern upon laser irradiation. Increasing the iron oxide core diameter resulted in a greater T2 relaxivity enhanced and nano-heating capabilities due to increased surface area. Increasing the gold nano-shell thickness resulted in a decreased efficiency as a nano-heater along with a decrease in T2 relaxivity. These results highlight the importance of identifying the key traits required when fabricating HNPs in order to tailor them to specific applications.

MRI of thiel‐embalmed human cadavers

To explain the observed considerable loss of signal and contrast when Thiel‐embalmed human cadavers are imaged using clinical magnetic resonance imaging (MRI) sequences, especially those based on spin‐echo MRI.

Synthesis, characterization and surface modification of ZnCrFeO4 nanoparticles

The aim of this research was to investigate zinc chromium ferrite (ZnCrFeO4) nanoparticles, synthesized using the sol gel technique with nanoparticle size controlled through a two-stage annealing process. Stage one was a low temperature firing which produced low quality nanocrystals with an average size of 15 nm. This was followed by a second firing stage at high temperature which enhanced the crystal quality. The nanoparticles were then coated with a bio-compatible shell to form a stable suspension in the ferrofluid carrier. The resulting nanoparticles were found by electron microscopy, atomic force microscopy and X-ray diffraction studies to have excellent crystal quality. The average size was 8.5 nm. Preliminary cell culture studies indicated the ZnCrFeO4 nanoparticles were non-toxic. The relatively high measured value of the relaxivity r2 showed that the nanoparticle coating was effective in substantially reducing aggregation and enhancing the properties of the nanoparticles associated with contrast enhancement in MRI.

Comparative ergonomic workflow and user experience analysis of MRI versus fluoroscopy-guided vascular interventions: an iliac angioplasty exemplar case study

PurposeA methodological framework is introduced to assess and compare a conventional fluoroscopy protocol for peripheral angioplasty with a new magnetic resonant imaging (MRI)-guided protocol. Different scenarios were considered during interventions on a perfused arterial phantom with regard to time-based and cognitive task analysis, user experience and ergonomics.MethodsThree clinicians with different expertise performed a total of 43 simulated common iliac angioplasties (9 fluoroscopic, 34 MRI-guided) in two blocks of sessions. Six different configurations for MRI guidance were tested in the first block. Four of them were evaluated in the second block and compared to the fluoroscopy protocol. Relevant stages’ durations were collected, and interventions were audio-visually recorded from different perspectives. A cued retrospective protocol analysis (CRPA) was undertaken, including personal interviews. In addition, ergonomic constraints in the MRI suite were evaluated.ResultsSignificant differences were found when comparing the performance between MRI configurations versus fluoroscopy. Two configurations [with times of 8.56 (0.64) and 9.48 (1.13) min] led to reduce procedure time for MRI guidance, comparable to fluoroscopy [8.49 (0.75) min]. The CRPA pointed out the main influential factors for clinical procedure performance. The ergonomic analysis quantified musculoskeletal risks for interventional radiologists when utilising MRI. Several alternatives were suggested to prevent potential low-back injuries.ConclusionsThis work presents a step towards the implementation of efficient operational protocols for MRI-guided procedures based on an integral and multidisciplinary framework, applicable to the assessment of current vascular protocols. The use of first-user perspective raises the possibility of establishing new forms of clinical training and education.

Characterisation of Mn0·7Zn0·3Fe2O4 nanoparticles prepared by two stage annealing

Abstract Nanoparticles of the spinel ferrite Mn0·7Zn0·3Fe2O4, with potential for use as contrast agents for magnetic resonance imaging applications, have been prepared by a sol–gel method followed by a two stage annealing process. The second stage of the annealing process improved the quality of the nanoparticles but also led to intergrown aggregates. The nanoparticles were milled to reduce this aggregation. After hand milling, the average nanoparticle size was 20 nm and after 5 h ball milling, the average nanoparticle size was 10 nm. The principal objectives of this study were to assess the effects of the two stage annealing process and milling on average nanoparticle size, crystal quality and magnetic properties relating to potential use in magnetic resonance imaging. Preliminary cytotoxicity measurements enabled assessment of possible nanoparticle contamination during milling on potential medical and clinical applications. A special surfactant was modified to disperse the nanoparticles in water and render them hydrophilic and to reduce agglomeration.