468 research outputs found
Methodological aspects of the SAVE data set
No full textThis paper describes the general design of the SAVE survey: the design of the questionnaire, inter-viewer and interviewee motivation, and the sampling designs of the various subsamples collected in 2001 and 2003. It discusses the representativeness of the data, explains the construction of weights, and provides probit regressions to analyse potential selectivity problems. The paper finishes by discussing implications for the use of the SAVE data in various estimation procedures.
A Hyperspectral Imaging System for Meningioma Grade Discrimination
No full textHistopathology is the gold standard for meningioma grading but is limited by processing time and subjectivity. We present a hyperspectral imaging system for real-time, label-free analysis, demonstrating the potential to enhance efficiency in meningioma grading. © 2025 The Author(s)
Characterization of lipid components in human cells by means of ATR FT-IR spectroscopy
No full textThe study of lipid components in human cells is of fundamental importance in many cellular functions, such as cell adhesion and migration, formation of membrane domain, DNA damage response, senescence, ageing autophagy, and apoptosis. For this reason, we investigated the different phospholipids and sphingolipids components of human cells by using Fourier Transform Infrared (FT-IR) spectroscopy that allows lipids detection and their characterization in biological samples. Commercial samples of phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidylinositol (PI), phosphatidylserine (PS), ceramide (Cer), ceramide 1-phosphate (C1P), sphingosine 1-phosphate (S1P) and sphingomyelin (SM) were used for collecting spectra using ATR acquisition mode. The infrared spectra of different lipids show the contribution of various functional groups from hydrocarbon chains and polar head groups. The present analysis of these spectra contributed to a better understanding of the characteristics of infrared spectra of single lipid components that can be considered a preliminary step in the FT-IR characterization of lipids extracts from human cells affected by pathologies or exposed to different external agents
Photodynamic Therapy Dose Planning for Peripheral Lung Cancer
No full textLung cancer is still responsible for approximately one fifth of cancer deaths worldwide and there is a rising trend in the number of cases that present themselves more diffusely in peripheral regions. Newer techniques, like photodynamic therapy (PDT) can help combat this disease. PDT dose planning requires knowledge of the optical properties of the tissue (TOP), the effect of internal structures (airways, blood) on the light distribution and the threshold value required to trigger cell death. In pig models with STEEN: mu_eff525=2.580 ± 0.275, mu_eff665=1.233 ± 0.072 and mu_eff808=0.756 ± 0.047; with blood: mu_eff525=2.664 ± 0.198, mu_eff665=1.820 ± 0.067 and mu_eff808=0.779 ± 0.066; in human with blood: mu_eff525=2.487 ± 0.233, mu_eff665=1.178 ± 0.197 and mu_eff808=1.057 ± 0.070. Using a Monte Carlo simulator: FullMonte, threshold values for healthy porcine lung tissue could be calculated: T= 3.53x10^17 ± 1.12x10^19 and T=1.46x10^17 ± 8.34x10^17.M.Sc
Integrated Microfluidic Optical Manipulation Technique: Towards High Throughput Single Cell Analysis
No full textAn all-optical micromanipulation technique is presented in the framework of precise cell selection within a cell culture and multiplexed transport capabilities for microfluidic single cell analysis applications. The technique was developed by combining an optical tweezer setup with a novel integrated waveguide cell propulsion method referred to as end-face waveguide propulsion (EFWP). The EFWP technique delivers optical forces to a particle generating thrust. The thesis is divided into two sections: simulation and experimental validation. In the first section a new simulation technique based on ray optics theory (ROT) and the beam propagation method (BPM) is used to predict particle velocity and trajectory along a microfluidic propagation channel. In this work, the ROT-BPM technique is used to analyse and optimize the waveguide geometry to maximize particle velocity. Analysis of the impact of common microchip manufacturing limitations on velocity is performed to determine acceptable fabrication process tolerances. The second section presents experimental results of polymer microspheres and acute myeloid leukemia (AML) cells as biological targets. The experimental results are compared with simulations performed in the first section. Correction factors are added to the simulations to reflect the experimental device parameters. Thermal e_ects due to photon absorption within the fluidic channels are also investigated and corrected for. The final analysis indicates that the ROT-BPM technique developed in this work can be used to adequately predict particle velocity and trajectory path. EFWP currently delivers the fastest particle velocities compared to other optical micromanipulation techniques currently available in microfluidic applications. While the technique is focused on addressing chemical cytometry precise particle selectivity and high throughput needs, EFWP can also be used in many other single cell applications.Ph
Implementation of a Spatially-resolved Explicit Photodynamic Therapy Dosimetry System Utilizing Multi-sensor Fiber Optic Probes
No full textPhotodynamic Therapy (PDT) has proven to be a minimally invasive alternative treatment option for various conditions including cancer. The treatment efficacy of deep-seated tumours with PDT is variable, compared to the treatment of tissue surfaces such as the skin and esophagus. This is partly due to inadequate monitoring of the three interrelated treatment parameters: treatment light, photosensitizer and tissue oxygenation. This thesis presents the development of a system for explicit dosimetry of PDT treatment light and tissue oxygenation using multi-sensor fiber optic probes for spatially resolved parameter measurements. The system uses embedded fluorescent sensors for treatment light quantification. Tissue oxygenation measurement is accomplished using frequency domain techniques with embedded phosphorescent metalloporphyrin compounds as sensors.MAS
Biological and Physical Strategies to Improve the Therapeutic Index of Photodynamic Therapy
No full textPhotodynamic therapy (PDT) derives its tumour selectivity from preferential photosensitizer accumulation and short light penetration in tissue.
However, additional strategies are needed to improve the therapeutic index of PDT in oncological applications where light is delivered interstitially to large volumes (e.g. prostate), or when adjacent normal tissue is extremely sensitive (e.g. brain).
Much research to improve PDT's selectivity is directed towards developing targeted photosensitizers. Here, I present two alternative strategies to improve PDT's selectivity, without compromising its efficacy. For interstitial delivery, I investigated whether customizable cylindrical diffusers can be used to deliver light doses that conform better to target geometries, specifically the prostate. Additionally, I examined whether the neuroprotectant erythropoietin, used as an adjuvant to PDT for brain tumours, can reduce the sensitivity of normal tissue, thereby improving treatment selectivity.
To determine if tailored diffusers constitute an improvement over conventional ones, I introduce a novel optimization algorithm for treatment planning.
I also analyze the sensitivity of the resulting plans to changes in the optical properties and diffuser placement. These results are contextualized by a mathematical formalism to characterize the light dose distributions arising from tailored diffusers. In parallel, I investigate the neuroprotective effects of erythropoietin in PDT of primary cortical neurons in culture and normal rat brain in vivo.
I show that the most important parameter determining prostate coverage is the number of diffusers employed. Moreover, while tailored diffusers do offer an improvement over conventional ones, the improvement is likely masked by perturbations introduced by the uncertainties of light delivery. Although these results largely discard the use of tailored diffusers in prostate PDT, significant insight has been gained into PDT treatment planning, and tailored diffusers may still be advantageous in more complicated geometries. Additionally, I show that erythropoietin does not improve survival of PDT-treated neurons PDT, nor reduces the volume of necrosis in vivo, for the ranges of conditions and doses studied. To our knowledge, this is the first time this strategy has been tested in brain PDT and deserves to be investigated further, by using later time-points, functional outcomes, and other neuroprotectants.Ph
Integrated Microfluidic Optical Manipulation Technique: Towards High Throughput Single Cell Analysis
No full textAn all-optical micromanipulation technique is presented in the framework of precise cell selection within a cell culture and multiplexed transport capabilities for microfluidic single cell analysis applications. The technique was developed by combining an optical tweezer setup with a novel integrated waveguide cell propulsion method referred to as end-face waveguide propulsion (EFWP). The EFWP technique delivers optical forces to a particle generating thrust. The thesis is divided into two sections: simulation and experimental validation. In the first section a new simulation technique based on ray optics theory (ROT) and the beam propagation method (BPM) is used to predict particle velocity and trajectory along a microfluidic propagation channel. In this work, the ROT-BPM technique is used to analyse and optimize the waveguide geometry to maximize particle velocity. Analysis of the impact of common microchip manufacturing limitations on velocity is performed to determine acceptable fabrication process tolerances. The second section presents experimental results of polymer microspheres and acute myeloid leukemia (AML) cells as biological targets. The experimental results are compared with simulations performed in the first section. Correction factors are added to the simulations to reflect the experimental device parameters. Thermal e_ects due to photon absorption within the fluidic channels are also investigated and corrected for. The final analysis indicates that the ROT-BPM technique developed in this work can be used to adequately predict particle velocity and trajectory path. EFWP currently delivers the fastest particle velocities compared to other optical micromanipulation techniques currently available in microfluidic applications. While the technique is focused on addressing chemical cytometry precise particle selectivity and high throughput needs, EFWP can also be used in many other single cell applications.Ph
Biological and Physical Strategies to Improve the Therapeutic Index of Photodynamic Therapy
No full textPhotodynamic therapy (PDT) derives its tumour selectivity from preferential photosensitizer accumulation and short light penetration in tissue.
However, additional strategies are needed to improve the therapeutic index of PDT in oncological applications where light is delivered interstitially to large volumes (e.g. prostate), or when adjacent normal tissue is extremely sensitive (e.g. brain).
Much research to improve PDT's selectivity is directed towards developing targeted photosensitizers. Here, I present two alternative strategies to improve PDT's selectivity, without compromising its efficacy. For interstitial delivery, I investigated whether customizable cylindrical diffusers can be used to deliver light doses that conform better to target geometries, specifically the prostate. Additionally, I examined whether the neuroprotectant erythropoietin, used as an adjuvant to PDT for brain tumours, can reduce the sensitivity of normal tissue, thereby improving treatment selectivity.
To determine if tailored diffusers constitute an improvement over conventional ones, I introduce a novel optimization algorithm for treatment planning.
I also analyze the sensitivity of the resulting plans to changes in the optical properties and diffuser placement. These results are contextualized by a mathematical formalism to characterize the light dose distributions arising from tailored diffusers. In parallel, I investigate the neuroprotective effects of erythropoietin in PDT of primary cortical neurons in culture and normal rat brain in vivo.
I show that the most important parameter determining prostate coverage is the number of diffusers employed. Moreover, while tailored diffusers do offer an improvement over conventional ones, the improvement is likely masked by perturbations introduced by the uncertainties of light delivery. Although these results largely discard the use of tailored diffusers in prostate PDT, significant insight has been gained into PDT treatment planning, and tailored diffusers may still be advantageous in more complicated geometries. Additionally, I show that erythropoietin does not improve survival of PDT-treated neurons PDT, nor reduces the volume of necrosis in vivo, for the ranges of conditions and doses studied. To our knowledge, this is the first time this strategy has been tested in brain PDT and deserves to be investigated further, by using later time-points, functional outcomes, and other neuroprotectants.Ph
Time resolved photon counting CMOS SPAD arrays for clinical imaging and spectroscopy
No full textSingle photon detection offers enhanced measurement through observation of timing dynamics on the picosecond to nanosecond scale. This has been widely exploited across many fields, including biological or medical technology. However practical application to clinic is often limited due to acquisition limitations of single point detectors combined with practical and cost limitations to employing larger numbers of detectors in combination. However, recent advancements in CMOS single photon avalanche diodes (SPADs) enable massively multiplexed time correlated single photon counting (TCSPC) in a compact format suitable for practical application. This work describes our efforts to employ this technology to enhance a range of technologies, including fibre optic spectroscopy, endoscopic imaging, and widefield clinical imaging. We have demonstrated multiple applications to improve signal to noise in fibre optic probes with this technology. This includes: improved Raman spectroscopy with single fibre optic probes through time resolved separation of unwanted background; better disambiguation of fluorescently labelled bacteria through fluorescent lifetime measurements in both spectroscopic and endoscopic imaging modalities; and fibre optic fluorescence spectroscopy of tissue autofluorescence indicating disease state. Further we detail a time resolved widefield imaging system applied to the observation of diffuse photons transmitted from fibre optic light sources placed deep within tissue (porcine and human cadavers), where transiting photons are observed from outside the body. This technology is now being translated to initial clinical investigation for locating inserted medical devices.</p
- …
