Raman spectroscopy as a PAT for pharmaceutical blending: Advantages and disadvantages.

Raman spectroscopy has been positively evaluated as a tool for the in-line and real-time monitoring of powder blending processes and it has been proved to be effective in the determination of the endpoint of the mixing, showing its potential role as process analytical technology (PAT). The aim of this study is to show advantages and disadvantages of Raman spectroscopy with respect to the most traditional HPLC analysis. The spectroscopic results, obtained directly on raw powders, sampled from a two-axis blender in real case conditions, were compared with the chromatographic data obtained on the same samples. The formulation blend used for the experiment consists of active pharmaceutical ingredient (API, concentrations 6.0% and 0.5%), lactose and magnesium stearate (as excipients). The first step of the monitoring process was selecting the appropriate wavenumber region where the Raman signal of API is maximal and interference from the spectral features of excipients is minimal. Blend profiles were created by plotting the area ratios of the Raman peak of API (AAPI) at 1598cm-1 and the Raman bands of excipients (AEXC), in the spectral range between 1560 and 1630cm-1, as a function of mixing time: the API content can be considered homogeneous when the time-dependent dispersion of the area ratio is minimized. In order to achieve a representative sampling with Raman spectroscopy, each sample was mapped in a motorized XY stage by a defocused laser beam of a micro-Raman apparatus. Good correlation between the two techniques has been found only for the composition at 6.0% (w/w). However, standard deviation analysis, applied to both HPLC and Raman data, showed that Raman results are more substantial than HPLC ones, since Raman spectroscopy enables generating data rich blend profiles. In addition, the relative standard deviation calculated from a single map (30 points) turned out to be representative of the degree of homogeneity for that blend time.

GPU-based physical cut in interactive haptic simulations.

PURPOSE: Interactive, physics based, simulations of deformable bodies are a growing research area with possible applications to computer-aided surgery. Their aim is to create virtual environments where surgeons are free to practice. To ensure the needed realism, the simulations must be performed with deformable bodies. The goal of this paper is to describe the approach to the development of a physics-based surgical simulator with haptic feedback. METHOD: The main development issue is the representation of the organ behavior at the high rates required by haptic realism. Since even high-end computers have inadequate performance, our approach exploits the parallelism of modern Graphics Processing Units (GPU). Particular attention is paid to the simulation of cuts because of their great importance in the surgical practice and the difficulty in handling topological changes in real time. RESULTS: To prove the correctness of our approach, we simulated an interactive, physically based, virtual abdomen. The simulation allows the user to interact with deformable models. Deformable models are updated in real time, thus allowing the rendering of force feedback to the user. The method is optimized to handle high quality scenes: we report results of interactive simulation of two virtual tools interacting with a complex model. CONCLUSIONS: The integration of physics-based deformable models in simulations greatly increases the realism of the virtual environment, taking into account real tissue properties and allowing the user to feel the actual forces exerted by organs on virtual tools. Our method proves the feasibility of exploiting GPU to simulate deformable models in interactive virtual environments.

Preoperative workflow for lymph nodes staging.

PURPOSE: Accurate staging of lymph nodes relies mainly on surgical exploration and manual palpation. We present a new non-invasive diagnostic approach: simulated palpation through virtual laparoscopic instruments. METHODS: We set up a diagnostic process to extract lymph nodes shape and position from CTs and to analyze the trend of pixels intensities to determine tissue properties in order to feedback the force information. RESULTS: We have integrated the model, obtained from both the morphological information and stiffness values, in our laparoscopy simulator and surgeons can virtually palpate, with a haptic device, the lymph nodes. We evaluated the workflow extracting lymph nodes from a case study: the feedback provided through the simulator greatly helps the surgeon in the correct staging. CONCLUSIONS: Results show the feasibility of the approach and in the future we will clinically evaluate this new diagnostic methodology. We are studying the possibility to integrate CTs with other imaging systems to increase the accuracy.