Gabriela Apiou-Sbirlea

The use of combined single photon emission computed tomography and X-ray computed tomography to assess the fate of inhaled aerosol

BACKGROUND Gamma camera imaging is widely used to assess pulmonary aerosol deposition. Conventional planar imaging provides limited information on its regional distribution. In this study, single photon emission computed tomography (SPECT) was used to describe deposition in three dimensions (3D) and combined with X-ray computed tomography (CT) to relate this to lung anatomy. Its performance was compared to planar imaging. METHODS Ten SPECT/CT studies were performed on five healthy subjects following carefully controlled inhalation of radioaerosol from a nebulizer, using a variety of inhalation regimes. The 3D spatial distribution was assessed using a central-to-peripheral ratio (C/P) normalized to lung volume and for the right lung was compared to planar C/P analysis. The deposition by airway generation was calculated for each lung and the conducting airways deposition fraction compared to 24-h clearance. RESULTS The 3D normalized C/P ratio correlated more closely with 24-h clearance than the 2D ratio for the right lung [coefficient of variation (COV), 9% compared to 15% p < 0.05]. Analysis of regional distribution was possible for both lungs in 3D but not in 2D due to overlap of the stomach on the left lung. The mean conducting airways deposition fraction from SPECT for both lungs was not significantly different from 24-h clearance (COV 18%). Both spatial and generational measures of central deposition were significantly higher for the left than for the right lung. CONCLUSIONS Combined SPECT/CT enabled improved analysis of aerosol deposition from gamma camera imaging compared to planar imaging. 3D radionuclide imaging combined with anatomical information from CT and computer analysis is a useful approach for applications requiring regional information on deposition.

Non-invasive transdermal two-dimensional mapping of cutaneous oxygenation with a rapid-drying liquid bandage.

Oxygen plays an important role in wound healing, as it is essential to biological functions such as cell proliferation, immune responses and collagen synthesis. Poor oxygenation is directly associated with the development of chronic ischemic wounds, which affect more than 6 million people each year in the United States alone at an estimated cost of

Ventilator-Integrated Jet Nebulization Systems: Tidal Volume Control and Efficiency of Synchronization

25 billion. Knowledge of oxygenation status is also important in the management of burns and skin grafts, as well as in a wide range of skin conditions. Despite the importance of the clinical determination of tissue oxygenation, there is a lack of rapid, user-friendly and quantitative diagnostic tools that allow for non-disruptive, continuous monitoring of oxygen content across large areas of skin and wounds to guide care and therapeutic decisions. In this work, we describe a sensitive, colorimetric, oxygen-sensing paint-on bandage for two-dimensional mapping of tissue oxygenation in skin, burns, and skin grafts. By embedding both an oxygen-sensing porphyrin-dendrimer phosphor and a reference dye in a liquid bandage matrix, we have created a liquid bandage that can be painted onto the skin surface and dries into a thin film that adheres tightly to the skin or wound topology. When captured by a camera-based imaging device, the oxygen-dependent phosphorescence emission of the bandage can be used to quantify and map both the pO2 and oxygen consumption of the underlying tissue. In this proof-of-principle study, we first demonstrate our system on a rat ischemic limb model to show its capabilities in sensing tissue ischemia. It is then tested on both ex vivo and in vivo porcine burn models to monitor the progression of burn injuries. Lastly, the bandage is applied to an in vivo porcine graft model for monitoring the integration of full- and partial-thickness skin grafts.

Bioequivalence of inhaled drugs: fundamentals, challenges and perspectives

BACKGROUND: Jet nebulizers constitute the aerosolization devices most frequently used during mechanical ventilation. Continuous nebulization can influence the delivered tidal volume (VT) and lead to significant medication loss during expiration. Ventilators thus provide integrated jet nebulization systems that are synchronized during inspiration and ostensibly keep VT constant. METHODS: This was a bench study of systems integrated in the Evita XL, Avea, Galileo, and G5 ventilators. The VT delivered with and without nebulization, the inspiratory synchronization of nebulization, and the aerosol deposition were measured with 2 locations of the nebulizer. RESULTS: Changes in VT with the nebulizer were below 20 mL and below 10% of set VT for all ventilators. Synchronization was good at the beginning of insufflation, but prolonged nebulization was observed with all ventilators at the end of insufflation, until up to 1 s during expiration: 5–80% of nebulization occurred during expiration with significant aerosol loss in the expiratory limb. Synchrony could be improved by (1) reducing gas compression/decompression phenomena proximal to the jet nebulizer and (2) increasing inspiratory time, which reduced the amount of nebulization occurring during expiration. Placing the nebulizer upstream in the inspiratory limb did not affect inspiratory synchrony but allowed reduction of the amount of aerosol lost in the expiratory limb. CONCLUSIONS: Jet nebulizer systems integrated in the tested ventilators are reliable in terms of VT control. Gas compression in tubing driving gas to the nebulizer delays synchronization and reduces nebulization yield if the nebulizer is placed close to the Y-piece. Increasing inspiratory time with no end-inspiratory pause reduces the expiratory loss of medication if placement of the nebulizer upstream in the inspiratory limb is not feasible.

Numerical modelling of conductive and convective heat transfers in retinal laser applications

Interest in bioequivalence (BE) of inhaled drugs derives largely from the desire to offer generic substitutes to successful drug products. The complexity of aerosol dosage forms renders them difficult to mimic and raises questions regarding definitions of similarities and those properties that must be controlled to guarantee both the quality and the efficacy of the product. Despite a high level of enthusiasm to identify and control desirable properties there is no clear guidance, regulatory or scientific, for the variety of aerosol dosage forms, on practical measures of BE from which products can be developed. As more data on the pharmaceutical and clinical relevance of various techniques, as described in this review, become available, it is likely that a path to the demonstration of BE will become evident. In the meantime, debate on this topic will continue.

Influence of Choroidal Perfusion on Retinal Temperature Increase During Retinal Laser Treatments

The control of the temperature increase is an important issue in retinal laser treatments. Within the fundus of the eye heat, generated by absorption of light, is transmitted by diffusion in the retinal pigment epithelium and in the choroid and lost by convection due to the choroidal blood flow. The temperature can be spatially and temporally determined by solving the heat equation. In a former analytical model this was achieved by assuming uniform convection for the whole fundus of the eye. A numerical method avoiding this unrealistic assumption by considering convective heat transfer only in the choroid is used here to solve the heat equation. Numerical results are compared with experimental results obtained by using a novel method of noninvasive optoacoustic retinal temperature measurements in rabbits. Assuming global convection the perfusion coefficient was evaluated to 0.07 s(-1), whereas a value of 0.32 s(-1)--much closer to values found in the literature (between 0.28 and 0.30 s(-1))--was obtained when choroidal convection was assumed, showing the advantage of the numerical method. The modelling of retinal laser treatment is thus improved and could be considered in the future to optimize treatments by calculating retinal temperature increases under various tissues and laser properties.

Modeling of conductive and convective heat transfers in retinal laser treatments

In most retinal laser treatments the therapeutic effect is initiated by a transient temperature increase at and around the retinal pigment epithelium (RPE). Especially in long exposure time treatments like Transpupillary Thermotherapy (TTT) choroidal perfusion has a strong influence on the realized temperature at the fundus. The fundus blood circulation and therefore the heat dissipation is influenced by the intraocular pressure (IOP), which is investigated in the study presented here. In order to reduce the choroidal perfusion, the IOP is increased by injection of physiological saline solution into the eye of anaesthetized rabbits. The fundus is irradiated with 3.64 W/cm2 by means of a TTT-laser (λ = 810 nm) for t = 20 s causing a retinal temperature increase. Realtime temperature determination at the irradiated spot is achieved by a non invasive optoacoustic technique. Perfusion can be reduced by increasing IOP, which leads to different temperature increases when irradiating the retina. This should be considered for long time laser treatments.

Biomedical optics centers: forty years of multidisciplinary clinical translation for improving human health

Tumor thermo treatment such as photodynamic therapy (PDT) or transpupillary thermotherapy (TTT) deal with long term and large laser spot exposures. The induced temperature increase is not exactly known [1]. Under these conditions convective heat transfers due to the blood flow in the choroid and the choriocapillaris must be considered in addition to the usually calculated heat conduction. From an existing analytical model defining a unique convective term for the whole fundus irradiated with Gaussian irradiance distribution lasers [2], we developed a numerical one allowing a precise modelling of convection and calculating heating evolution and temperature profiles of the fundus of the eye. The aim of this study is to present the modelling and several comparisons between experimental results [3] and numerical ones concerning the convective heat transfers inside the fundus of the eye.

A wearable conformal bandage for non-invasive two-dimensional imaging of skin oxygenation(Conference Presentation)

Abstract. Despite widespread government and public interest, there are significant barriers to translating basic science discoveries into clinical practice. Biophotonics and biomedical optics technologies can be used to overcome many of these hurdles, due, in part, to offering new portable, bedside, and accessible devices. The current JBO special issue highlights promising activities and examples of translational biophotonics from leading laboratories around the world. We identify common essential features of successful clinical translation by examining the origins and activities of three major international academic affiliated centers with beginnings traceable to the mid-late 1970s: The Wellman Center for Photomedicine (Mass General Hospital, USA), the Beckman Laser Institute and Medical Clinic (University of California, Irvine, USA), and the Medical Laser Center Lübeck at the University of Lübeck, Germany. Major factors driving the success of these programs include visionary founders and leadership, multidisciplinary research and training activities in light-based therapies and diagnostics, diverse funding portfolios, and a thriving entrepreneurial culture that tolerates risk. We provide a brief review of how these three programs emerged and highlight critical phases and lessons learned. Based on these observations, we identify pathways for encouraging the growth and formation of similar programs in order to more rapidly and effectively expand the impact of biophotonics and biomedical optics on human health.

Special Section Guest Editorial: Translational biophotonics

The complex surface topology and soft mechanics of the skin poses a considerable challenge to the development of wearable, conformal sensors. As a results, current clinical assessments of healing-related skin parameters often rely on bulky and expensive optical systems that are difficult to deploy at the point of care. Here, using a rapid-drying, liquid bandage containing oxygen-sensing molecules, we created a wearable sensor bandage that conforms the surface geometry of skin and wounds, and provides two-dimensional maps of cutaneous oxygenation in a non-disruptive fashion. Custom oxygen sensing phosphors have been developed in house that are at least five times brighter than the commercial sensing molecules, enabling the visualization of oxygen concentration using a simple color camera or even by eye under ambient lighting conditions. The oxygen-sensing bandage has been applied to monitor tissue ischemia, graft integration, as well as the progression of burn in animal models. Recent studies have demonstrated its ability to track and quantify skin inflammation induced by complete Freund’s adjuvant in an in vivo porcine model.