Nanomedicines and microneedles: a guide to their analysis and application.

The fast-advancing progress in the research of nanomedicine and microneedle applications in the past two decades has suggested that the combination of the two concepts could help to overcome some of the challenges we are facing in healthcare. They include poor patient compliance with medication and the lack of appropriate administration forms that enable the optimal dose to reach the target site. Nanoparticles as drug vesicles can protect their cargo and deliver it to the target site, while evading the body's defence mechanisms. Unfortunately, despite intense research on nanomedicine in the past 20 years, we still haven't answered some crucial questions, e.g. about their colloidal stability in solution and their optimal formulation, which makes the translation of this exciting technology from the lab bench to a viable product difficult. Dissolvable microneedles could be an effective way to maintain and stabilise nano-sized formulations, whilst enhancing the ability of nanoparticles to penetrate the stratum corneum barrier. Both concepts have been individually investigated fairly well and many analytical techniques for tracking the fate of nanomaterials with their precious cargo, both in vitro and in vivo, have been established. Yet, to the best of our knowledge, a comprehensive overview of the analytical tools encompassing the concepts of microneedles and nanoparticles with specific and successful examples is missing. In this review, we have attempted to briefly analyse the challenges associated with nanomedicine itself, but crucially we provide an easy-to-navigate scheme of methods, suitable for characterisation and imaging the physico-chemical properties of the material matrix.

Speckle reduction using an artificial neural network algorithm.

This paper presents an algorithm for reducing speckle noise from optical coherence tomography (OCT) images using an artificial neural network (ANN) algorithm. The noise is modeled using Rayleigh distribution with a noise parameter, sigma, estimated by the ANN. The input to the ANN is a set of intensity and wavelet features computed from the image to be processed, and the output is an estimated sigma value. This is then used along with a numerical method to solve the inverse Rayleigh function to reduce the noise in the image. The algorithm is tested successfully on OCT images of Drosophila larvae. It is demonstrated that the signal-to-noise ratio and the contrast-to-noise ratio of the processed images are increased by the application of the ANN algorithm in comparison with the respective values of the original images.

Full-field thickness distribution of human tympanic membrane obtained with optical coherence tomography.

The full-field thickness distribution, three-dimensional surface model and general morphological data of six human tympanic membranes are presented. Cross-sectional images were taken perpendicular through the membranes using a high-resolution optical coherence tomography setup. Five normal membranes and one membrane containing a pathological site are included in this study. The thickness varies strongly across each membrane, and a great deal of inter-specimen variability can be seen in the measurement results, though all membranes show similar features in their respective relative thickness distributions. Mean thickness values across the pars tensa ranged between 79 and 97 µm; all membranes were thinnest in the central region between umbo and annular ring (50-70 µm), and thickness increased steeply over a small distance to approximately 100-120 µm when moving from the central region either towards the peripheral rim of the pars tensa or towards the manubrium. Furthermore, a local thickening was noticed in the antero-inferior quadrant of the membranes, and a strong linear correlation was observed between inferior-posterior length and mean thickness of the membrane. These features were combined into a single three-dimensional model to form an averaged representation of the human tympanic membrane. 3D reconstruction of the pathological tympanic membrane shows a structural atrophy with retraction pocket in the inferior portion of the pars tensa. The change of form at the pathological site of the membrane corresponds well with the decreased thickness values that can be measured there.

Multidimensional en-face OCT imaging of the retina.

Fast T-scanning (transverse scanning, en-face) was used to build B-scan or C-scan optical coherence tomography (OCT) images of the retina. Several unique signature patterns of en-face (coronal) are reviewed in conjunction with associated confocal images of the fundus and B-scan OCT images. Benefits in combining T-scan OCT with confocal imaging to generate pairs of OCT and confocal images similar to those generated by scanning laser ophthalmoscopy (SLO) are discussed in comparison with the spectral OCT systems. The multichannel potential of the OCT/SLO system is demonstrated with the addition of a third hardware channel which acquires and generates indocyanine green (ICG) fluorescence images. The OCT, confocal SLO and ICG fluorescence images are simultaneously presented in a two or a three screen format. A fourth channel which displays a live mix of frames of the ICG sequence superimposed on the corresponding coronal OCT slices for immediate multidimensional comparison, is also included. OSA ISP software is employed to illustrate the synergy between the simultaneously provided perspectives. This synergy promotes interpretation of information by enhancing diagnostic comparisons and facilitates internal correction of movement artifacts within C-scan and B-scan OCT images using information provided by the SLO channel.

Statistics of the depth-scan photocurrent in time-domain optical coherence tomography.

We derive the time-variant second-order statistics of the depth-scan photocurrent in time-domain optical coherence tomography (TD-OCT) systems using polarized thermal light sources and superluminescent diodes (SLDs). Since the asymptotic-joint-probability-distribution function (JPDF) of the photocurrent due to polarized thermal light is Gaussian and the signal-noise-ratio in TD-OCT is typically high (>80 dB), the JPDF of the depth-scan photocurrent could be approximated as a Gaussian random process that is completely determined by its second-order statistics. We analyze both direct and differential light detection schemes and include the effect of electronic thermal fluctuations. Our results are a necessary prerequisite for future development of statistical image processing techniques for TD-OCT.

Investigations of the eye fundus using a simultaneous optical coherence tomography/indocyanine green fluorescence imaging system.

We develop a dual-channel optical coherence tomography/indocyanine green (OCT/ICG) fluorescence system based on our previously reported ophthalmic OCT/confocal imaging system. The confocal channel is tuned to the fluorescence wavelength range of the ICG dye and light from the same optical source is used to generate the OCT image and to excite the ICG fluorescence. The system enables the clinician to visualize simultaneously en face OCT slices and corresponding ICG angiograms of the ocular fundus, displayed side by side. C-scan (constant depth) and B-scan (cross section) images are collected by fast en face scanning (T-scan). The pixel-to-pixel correspondence between the OCT and angiography images enables the user to precisely capture OCT B-scans at selected points on the ICG confocal images.

Imaging the retina by en face optical coherence tomography.

PURPOSE: To present the possibilities of a new system that combines optical coherence tomography (OCT) and confocal ophthalmoscopy, producing en face OCT images in patients with retinal diseases. METHODS: A prototype OCT Ophthalmoscope (OTI, Toronto, Canada) was used to scan patients with retinal conditions. The system uses a super luminescent diode (lambda = 820 nm; Deltalambda = 20 nm) and currently scans at a rate of 2 frames per second. In each frame, the OCT Ophthalmoscope simultaneously produces a transversal OCT scan and a confocal image in the X/Y plane. Both images correspond pixel to pixel. RESULTS: Between January 2002 and August 2003, >800 patients with various retinal diseases were scanned with the OCT Ophthalmoscope. Illustrative cases with regularly seen macular diseases are presented, such as macular hole and central serous retinopathy. CONCLUSION: Current difficulties as well as future possibilities of this new en face OCT ophthalmoscope are discussed. By presenting normal and pathologic transversal OCT images made by a prototype OCT Ophthalmoscope, we show that it can provide information not available using conventional OCT imaging.