The theory of task-based assessment of image quality is reviewed in the context of imaging with ionizing radiation, and objective figures of merit (FOMs) for image quality are summarized. The variation of the FOMs with the task, the observer and especially with the mean number of photons recorded in the image is discussed. Then various standard methods for specifying radiation dose are reviewed and related to the mean number of photons in the image and hence to image quality. Current knowledge of the relation between local radiation dose and the risk of various adverse effects is summarized, and some graphical depictions of the tradeoffs between image quality and risk are introduced. Then various dose-reduction strategies are discussed in terms of their effect on task-based measures of image quality.
The calculation of radiation dose from internally incorporated radionuclides is based on so-called absorbed fractions (AFs) and specific absorbed fractions (SAFs). SAFs for monoenergetic electrons were calculated for 63 source regions and 67 target regions using the new male and female adult reference computational phantoms adopted by the ICRP and ICRU and the Monte Carlo radiation transport programme package EGSnrc. The SAF values for electrons are opposed to the simplifying assumptions of ICRP Publication 30. The previously applied assumption of electrons being fully absorbed in the source organ itself is not always true at electron energies above approximately 300-500 keV. High-energy electrons have the ability to leave the source organ and, consequently, the electron SAFs for neighbouring organs can reach the same magnitude as those for photons for electron energies above 1 MeV. The reciprocity principle known for photons can be extended to electron SAFs as well, thus making cross-fire electron SAFs mass-independent. To quantify the impact of the improved electron dosimetry in comparison to the dosimetry using the simple assumptions of ICRP Publication 30, absorbed doses per administered activity of three radiopharmaceuticals were evaluated with and without explicit electron transport. The organ absorbed doses per administered activity for the two evaluation methods agree within 2%-3% for most organs for radionuclides with decay spectra having electron energies below a few hundred keV and within approximately 20% if higher electron energies are involved. An important exception is the urinary bladder wall, where the dose is overestimated by 60-150% using the simplified ICRP 30 approach for the radiopharmaceuticals of this study.
Accurate in vivo localisation of minimal amounts of functionalised gold-nanoparticles, enabling e.g. early-tumour diagnostics and pharmacokinetic tracking studies, requires a precision imaging system offering very high sensitivity, temporal and spatial resolution, large depth penetration, and arbitrarily long serial measurements. X-ray fluorescence imaging could offer such capabilities; however, its utilisation for human-sized scales is hampered by a high intrinsic background level. Here we measure and model this anisotropic background and present a spatial filtering scheme for background reduction enabling the localisation of nanoparticle-amounts as reported from small-animal tumour models. As a basic application study towards precision pharmacokinetics, we demonstrate specific localisation to sites of disease by adapting gold-nanoparticles with small targeting ligands in murine spinal cord injury models, at record sensitivity levels using sub-mm resolution. Both studies contribute to the future use of molecularly-targeted gold-nanoparticles as next-generation clinical diagnostic and pharmacokinetic tools.
Proton transfer reaction mass spectrometry (PTR-MS) has been used to analyze the volatile organic compounds (VOCs) emitted by in-vitro cultured human cells. For this purpose, two pairs of cancerous and non-cancerous human cell lines were selected:1. lung epithelium cells A-549 and retinal pigment epithelium cells hTERT-RPE1, cultured in different growth media; and 2. squamous lung carcinoma cells EPLC and immortalized human bronchial epithelial cells BEAS2B, cultured in identical growth medium. The VOCs in the headspace of the cell cultures were sampled: 1. online by drawing off the gas directly from the culture flask; and 2. by accumulation of the VOCs in PTFE bags connected to the flask for at least 12 h. The pure media were analyzed in the same way as the corresponding cells in order to provide a reference. Direct comparison of headspace VOCs from flasks with cells plus medium and from flasks with pure medium enabled the characterization of cell-line-specific production or consumption of VOCs. Among all identified VOCs in this respect, the most outstanding compound was m/z = 45 (acetaldehyde) revealing significant consumption by the cancerous cell lines but not by the non-cancerous cells. By applying multivariate statistical analysis using 42 selected marker VOCs, it was possible to clearly separate the cancerous and non-cancerous cell lines from each other.
Breath gas analysis is a promising technology for medical applications. By identifying disease-specific biomarkers in the breath of patients, a non-invasive and easy method for early diagnosis or therapy monitoring can be developed. In order to achieve this goal, one essential prerequisite is the reproducibility of the method applied, i.e. the quantification of exhaled volatile organic compounds (VOCs). The variability of breath gas VOC measurements can be affected by many factors. In this respect, sampling-specific parameters like flow rate and volume of exhalation, exhalation with or without breath holding, exhalation in single or multiple breathing and volume of air inhaled before breath gas exhalation can play a vital role. These factors affecting the measurements must be controlled by optimizing the sampling procedure. For such an optimization, it is important to know how exactly the different parameters affect the exhaled VOC concentrations. Therefore, a study has been undertaken in order to identify some effects of different breath sampling-specific parameters on the exhaled VOC profile using the mixed expired breath sampling technique. It was found that parameters such as filling the sampling bag with high or low flow rate of exhalation, with multiple or single exhalations, in different volumes of exhalation, with breath holding and under different surrounding air conditions significantly affect the concentrations of the exhaled VOCs. Therefore, the specific results of this work should be taken into account before planning new breath gas studies or developing new breath gas collection systems in order to minimize the number of artefacts affecting the concentration of exhaled VOCs.
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