Impact of yttrium-90 microsphere density, flow dynamics, and administration technique on spatial distribution: analysis using an in vitro model

Purpose: To investigate material density, flow, and viscosity effects on microsphere distribution within an in vitro model designed to simulate hepatic arteries.Materials and Methods: A vascular flow model was used to compare distribution of glass and resin surrogates in a clinically derived flow range (60–120 mL/min). Blood-mimicking fluid (BMF) composed of glycerol and water (20%–50% vol/vol) was used to simulate a range of blood viscosities. Microsphere distribution was quantified gravimetrically, and injectate solution was dyed to enable quantification by UV spectrophotometry. Microsphere injection rate (5–30 mL/min) and the influence of contrast agent dilution of injection solution (0%–60% vol/vol) were also investigated.Results: No significant differences in behavior were observed between the glass and resin surrogate materials under any tested flow conditions (P = .182; n = 144 injections). Microspheres tend to align more consistently with the saline injection solution (r2 = 0.5712; n = 144) compared with total BMF flow distribution (r2 = 0.0104; n = 144). The most predictable injectate distribution (ie, greatest alignment with BMF flow, &lt; 5% variation) was demonstrated with &gt; 10-mL/min injection rates of pure saline solution, although &lt; 20% variation with glass microsphere distribution was observed with injection solution containing as much as 30% contrast medium when injected at &gt; 20 mL/min.Conclusions: Glass and resin yttrium-90 surrogates demonstrated similar distribution in a range of clinically relevant flow conditions, suggesting that microsphere density does not have a significant influence on microsphere distribution. Injection parameters that enhanced the mixing of the spheres with the BMF resulted in the most predictable distribution.<br/

Researching outside the box: Welcoming innovative qualitative inquiry to nurse education today

I would like to begin by thanking Billy Lauder for inviting me to write this editorial, following my recent appointment to the NET International Advisory Board. My first aim in what follows is to make some critical comments about trends I have seen in published qualitative research articles over the years of my involvement with NET and other mainstream international nursing journals. In this regard, I speak as a qualitative research teacher, supervisor, article and book writer, and peer reviewer and past editorial board member of journals in and beyond the discipline of nursing. On the basis of these critical comments, my second aim is to argue the need for an increase in innovative qualitative articles in NET. This will bring our journal more into line with the developing state of the art global picture of qualitative inquiry, evident in recent years in journals informing wider interdisciplinary fields in the social and human sciences and the humanities. I believe that such a broadening of scope can only enhance the status of NET as a world leader in creative nurse educational research and scholarship. In the light of these two aims, again responding to a request from Billy, I will end my editorial by describing related amendments to the journal’s article guidelines for authors on structuring innovative qualitative articles, and a corresponding increase in peer reviewers, appropriate for the task ahead

Characterizing geomorphological change to support sustainable river restoration and management

The hydrology and geomorphology of most rivers has been fundamentally altered through a long history of human interventions including modification of river channels, floodplains, and wider changes in the landscape that affect water and sediment delivery to the river. Resultant alterations in fluvial forms and processes have negatively impacted river ecology via the loss of physical habitat, disruption to the longitudinal continuity of the river, and lateral disconnection between aquatic, wetland, and terrestrial ecosystems. Through a characterization of geomorphological change, it is possible to peel back the layers of time to investigate how and why a river has changed. Process rates can be assessed, the historical condition of rivers can be determined, the trajectories of past changes can be reconstructed, and the role of specific human interventions in these geomorphological changes can be assessed. To achieve this, hydrological, geomorphological, and riparian vegetation characteristics are investigated within a hierarchy of spatial scales using a range of data sources. A temporal analysis of fluvial geomorphology supports process-based management that targets underlying problems. In this way, effective, sustainable management and restoration solutions can be developed that recognize the underlying drivers of geomorphological change, the constraints imposed on current fluvial processes, and the possible evolutionary trajectories and timelines of change under different future management scenarios. Catchment/river basin planning, natural flood risk management, the identification and appraisal of pressures, and the assessment of restoration needs and objectives would all benefit from a thorough temporal analysis of fluvial geomorphology

Applied biomimetic microfluidics for embolisation applications: towards the reduction of animal models for therapeutic evaluation of embolic agents

In vitro testing is a powerful tool for evaluating the performance of medical devices. This thesis presents the application of biomimetic microfluidic devices for in vitro characterisation of embolic microspheres, with respect to clinically inspired case-studies of the treatment of hyper-vascularised tumours.A comprehensive literature review of in vitro characterisation methods identified areas of potential research associated with the flow distribution, physical attributes and drug delivery capabilities of embolic agents. Flow devices were designed to replicate sections of hepatic architecture; initially focusing on embolic penetration efficacy, and then expanding to involve circular channels of various sizes representative of human blood vessels.Microfluidic testing was integrated into the development of novel radiopaque microspheres, providing novel assessment criteria for the selection of physicochemical attributes and aiding effective translation from in vitro to first-in-human studies. An in vitro vascular network device was then refined through collaboration with treating physicians and utilised for novel emulsion characterisation, as part of a pre-clinical screening study. Pharmacokinetic trends and handling investigated in this study enabled confirmation of performance behaviour predicted in vitro. To account for microvascular flow effects, a device representative of 3rd order hepatic bifurcations was utilised to investigate distribution of drug loaded embolics under clinically relevant flow conditions. Computational Fluid Dynamic modelling was applied for in silico prediction according to empirical observations indicating preliminary prediction capabilities.In vitro drug elution in respect to core bead chemistry, size and dose density at the point of catheter delivery was investigated. Reported elution trends indicated the highest statistical level of in vitro – in vivo correlation with pre-clinical studies, providing better understanding of systemic plasma profiles generated in vivo. A separate gel model representative of porcine parenchymal tissue was employed to investigate the effects of external focused ultrasound on contact based drug diffusion. Diffusion rate was shown to be higher for non-radiopaque, smaller beads, aligned with findings from previous freeflowing elution models.Finally, a case-study investigated the in vitro flow distribution of radioembolic microspheres with respect to particle density and the application of contrast agent concurrent to microsphere administration. The investigation was able to show that material density was not the overriding factor influencing distribution and a novel administration protocol combining contrast agent with saline injections for potential intra-procedural visualisation was proposed.Overall, this thesis utilises novel compartmentalised in vitro devices to characterise embolic agent attributes, enable development of predictive models and provide potential methods for the reduction of animal testing. Devices and methods were incorporated into clinically inspired casestudies to demonstrate relevance and application to the field of interventional oncology

Esophageal obstruction due to enteral feed bezoar: A case report and literature review

This paper describes a rare complication of enteral feeding, esophageal obstruction due to feeding formula bezoar, and reviews the published cases. An attempt to re-insert the nasogastric tube in a chronically ventilated 80-year-old female fed via a nasogastric tube with Jevity® failed. An esophagogastroduodenoscopy revealed an 18 cm-long concretion of the feeding formula, filling most of the esophageal lumen, which was removed endoscopically. Forty-two cases of feeding formula esophageal bezoars have been reported in the literature. The formation of feeding formula bezoars is triggered by acidic gastroesophageal reflux. The acidic pH in the esophagus causes clotting of the casein in the formula. Predisposing factors for bezoar formation are: mechanical ventilation, supine position, neurological diseases, diabetes mellitus, hypothyroidism, obesity and history of partial gastrectomy. Diagnosis and removal of the bezoar is done endoscopically. Feeding in a semi-recumbent position, administration of prokinetic agents and proton pump inhibitors may prevent this complication

Review of the development of methods for characterization of microspheres for use in embolotherapy: translating Bench to Cathlab

Therapeutic embolotherapy is the deliberate occlusion of a blood vessel within the body, which can be for the prevention of internal bleeding, stemming of flow through an arteriovenous malformation, or occlusion of blood vessels feeding a tumour. This is achieved using a wide selection of embolic devices such as; balloons, coils, gels, glues and particles.Particulate embolization is often favoured for blocking smaller vessels, particularly within hyper-vascularised tumours, as they are available in calibrated sizes and can be delivered distally via microcatheters for precise occlusion with associated locoregional drug delivery.Embolic performance has been traditionally evaluated using animal models, but with increasing interest in the 3R’s (Replacement, Reduction, Refinement), manufacturers, regulators and clinicians have shown interest in the development of more sophisticated in vitro methods for evaluation and prediction of in vivo performance. Herein we review the current progress in developing bespoke techniques incorporating; physical handling, fluid dynamics, occlusive behaviour and sustained drug elution kinetics within vascular systems.Whilst it is necessary to continue to validate the safety of such devices in vivo, great strides have been made in the development of bench tests that better predict the behaviour of these products aligned with the principles of the 3R’s

Spatiotemporal dynamics of doxorubicin elution from embolic beads within a microfluidic network

Anticancer treatment using embolic drug-eluting beads (DEBs) has shown multifarious advantages compared to systemic chemotherapy. However, there is a growing need for a better understanding of the physical parameters governing drug-elution from embolic devices under physiologically relevant fluidic conditions. In the present study, we investigated the spatiotemporal dynamics of doxorubicin hydrochloride elution from drug-loaded hydrogel embolic beads within a microfluidic device consisting of a network of interconnected microchannels which replicates the architectural properties of microvascular systems. Drug-elution has been investigated experimentally at a single-bead level, using in-house developed microscopy- and spectrofluorimetry-based methods. Results demonstrated that the kinetics of drug-elution and the amount of eluted drug strongly depended on the location of the embolic event within the embolised channel (e.g. fractional amount of eluted drug after 3 h was equal to ~ 0.2 and ~ 0.6 for completely-confined and partially-confined bead, respectively). Drug-elution from partially-confined bead showed a counterintuitive dependence on the local Reynolds number (and thus on the mean fluid velocity), as a result of dynamic changes in bead compressibility causing the displacement of the bead from the primary embolic site. Conversely, the kinetics of drug-elution from fully-confined bead was less affected by the local Reynolds number and bead displayed faster elution from the surface area exposed to the systemic flow, which was associated with the formation of fluid eddies nearby the bead post embolisation