| 1. |
- Asplund, Sara, 1976, et al.
(författare)
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Extended analysis of the effect of learning with feedback on the detectability of pulmonary nodules in chest tomosynthesis
- 2011
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Ingår i: Progress in Biomedical Optics and Imaging - Proceedings of SPIE. - : SPIE. - 1605-7422. ; 7966
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In chest tomosynthesis, low-dose projections collected over a limited angular range are used for reconstruction of section images of the chest, resulting in a reduction of disturbing anatomy at a moderate increase in radiation dose compared to chest radiography. In a previous study, we investigated the effects of learning with feedback on the detection of pulmonary nodules in chest tomosynthesis. Six observers with varying degrees of experience of chest tomosynthesis analyzed tomosynthesis cases for presence of pulmonary nodules. The cases were analyzed before and after learning with feedback. Multidetector computed tomography (MDCT) was used as reference. The differences in performance between the two readings were calculated using the jackknife alternative free-response receiver operating characteristics (JAFROC-2) as primary measure of detectability. Significant differences between the readings were found only for observers inexperienced in chest tomosynthesis. The purpose of the present study was to extend the statistical analysis of the results of the previous study, including JAFROC-1 analysis and FROC curves in the analysis. The results are consistent with the results of the previous study and, furthermore, JAFROC-1 gave lower p-values than JAFROC-2 for the observers who improved their performance after learning with feedback. © 2011 SPIE.
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| 2. |
- Balbekin, N.S., et al.
(författare)
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Nondestructive monitoring of aircraft composites using terahertz radiation
- 2014
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Ingår i: Progress in Biomedical Optics and Imaging - Proceedings of SPIE. - : SPIE. - 1605-7422. - 9781628415643 ; 9448, s. 94482D-
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Konferensbidrag (refereegranskat)abstract
- In this paper we consider using the terahertz (THz) time domain spectroscopy (TDS) for non destructive testing and determining the chemical composition of the vanes and rotor-blade spars. A versatile terahertz spectrometer for reflection and transmission has been used for experiments. We consider the features of measured terahertz signal in temporal and spectral domains during propagation through and reflecting from various defects in investigated objects, such as voids and foliation. We discuss requirements are applicable to the setup and are necessary to produce an image of these defects, such as signal-to-noise ratio and a method for registration THz radiation. Obtained results indicated the prospects of the THz TDS method for the inspection of defects and determination of the particularities of chemical composition of aircraft parts.
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| 3. |
- Bauer, Brigitte, 1978, et al.
(författare)
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Metal nanoparticles amplify photodynamic effect on skin cells in vitro
- 2011
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Ingår i: Progress in Biomedical Optics and Imaging - Proceedings of SPIE. Optical Interactions with Tissue and Cells XXII; San Francisco, CA; 24-26 January 2011. - : SPIE. - 1605-7422. - 9780819484345 ; 7897
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- We report on an investigation aimed to increase the efficiency of photodynamic therapy (PDT) through the influence of localized surface plasmon resonances (LSPR's) in metal nanoparticles. PDT is based on photosensitizers that generate singlet oxygen at the tumour site upon exposure to visible light. Although PDT is a well-established treatment for skin cancer, a major drawback is the low quantum yield for singlet-oxygen production. This motivates the development of novel methods that enhance singlet oxygen generation during treatment. In this context, we study the photodynamic effect on cultured human skin cells in the presence or absence of gold nanoparticles with well established LSPR and field-enhancement properties. The cultured skin cells were exposed to protoporphyrin IX and gold nanoparticles and subsequently illuminated with red light. We investigated the differences in cell viability by tuning different parameters, such as incubation time and light dose. In order to find optimal parameters for specific targeting of tumour cells, we compared normal human epidermal keratinocytes with a human squamous skin cancer cell line. The study indicates significantly enhanced cell death in the presence of nanoparticles and important differences in treatment efficiency between normal and tumour cells. These results are thus promising and clearly motivate further development of nanoparticle enhanced clinical PDT treatment.
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| 4. |
- Borglin, Johan, 1986, et al.
(författare)
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Improving multiphoton microscopy using annular beam shaping, focusing on imaging of human skin
- 2014
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Ingår i: Multiphoton Microscopy in the Biomedical Sciences XIV: 2-4 February 2014, San Francisco, California, United States. Progress in Biomedical Optics and Imaging - Proceedings of SPIE. - : SPIE. - 1605-7422. ; 8948
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Konferensbidrag (refereegranskat)abstract
- Multiphoton fluorescence microscopy (MPM) is a method for high resolution, non-invasive investigations of biological tissue. The aim of introducing an annular shaped laser beam is to reduce the ouf-of-focus generated background signal improving imaging of light scattering tissue such as human skin. Simulations show that 50% of the beam radius can be blocked, while preserving the shape of the point spread function. Initial experiments performed on a phantom consisting of fluorescein and fluorescent beads embedded in agar by using a custom built MPM-set up show that by introducing a simple beam blocker to create an annular beam, the background signal is reduced with approximately 5%. Future work will include optimizing the set up, and creating phantoms with more light scattering properties. © 2014 SPIE.
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| 5. |
- Daeichin, Verya, 1984, et al.
(författare)
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Self-demodulation effect on subharmonic response of ultrasound contrast agent
- 2012
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Ingår i: Progress in Biomedical Optics and Imaging - Proceedings of SPIE. - : SPIE. - 1605-7422. - 9780819489692 ; 8320, s. Art. no. 83200W-
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Konferensbidrag (refereegranskat)abstract
- In this work the use of the self-demodulation (S-D) signal as a mean of microbubble excitation at the subharmonic (SH) frequency to enhance the SH emission of ultrasound contrast agent (UCA) is studied. SH emission from the UCA is of interest since it is produced only by the UCA and is free of the artifacts produced in harmonic imaging modes. The S-D wave is a low-frequency signal produced by nonlinear propagation of an ultrasound wave in the medium. Single element transducer experiments and numerical simulations were conducted at 10 MHz to study the effect of the S-D signal on the SH response of the UCA by modifying the envelope of the excitation bursts. For 6 and 20 transmitted cycles, the SH response is increased up to 25 dB and 22 dB because of the S-D stimulation for a burst with a rectangular envelope compared with a Gaussian envelope burst. Such optimized excitations were used in an array-based micro-ultrasound system (Vevo 2100, VisualSonics Inc., Toronto, ON, Canada) at 18 MHz for in vitro validation of SH imaging. This study suggests that a suitable design of the envelope of the transmit excitation to generate a S-D signal at the SH frequency can enhance the SH emission of UCA and real-time SH imaging is feasible with shorter transmit burst (6- cycle) and low acoustic pressure (-150 KPa) at high frequencies (>15 MHz).
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| 6. |
- Ehteshami Bejnordi, B., et al.
(författare)
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Novel chromatin texture features for the classification of Pap smears
- 2013
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Ingår i: Progress in Biomedical Optics and Imaging - Proceedings of SPIE. - : SPIE. - 1605-7422. - 9780819494504 ; 8676, s. Art. no. 867608-
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Konferensbidrag (refereegranskat)abstract
- This paper presents a set of novel structural texture features for quantifying nuclear chromatin patterns in cells on a conventional Pap smear. The features are derived from an initial segmentation of the chromatin into bloblike texture primitives. The results of a comprehensive feature selection experiment, including the set of proposed structural texture features and a range of different cytology features drawn from the literature, show that two of the four top ranking features are structural texture features. They also show that a combination of structural and conventional features yields a classification performance of 0.954±0.019 (AUC±SE) for the discrimination of normal (NILM) and abnormal (LSIL and HSIL) slides. The results of a second classification experiment, using only normal-appearing cells from both normal and abnormal slides, demonstrates that a single structural texture feature measuring chromatin margination yields a classification performance of 0.815±0.019. Overall the results demonstrate the efficacy of the proposed structural approach and that it is possible to detect malignancy associated changes (MACs) in Papanicoloau stain.
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| 7. |
- Enejder, Annika, 1969, et al.
(författare)
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CARS and SHG microscopy of artificial bioengineered tissues
- 2010
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Ingår i: Progress in Biomedical Optics and Imaging - Proceedings of SPIE. - : SPIE. - 1605-7422. - 9780819479655 ; 7569
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Major efforts are presently made to develop artificial replacement tissues with optimal architectural and material characteristics, mimicking those of their natural correspondents. Encouraged by the readiness with which cellulose fibers woven by the bacteria Acetobacter xylinum can be formed into organ-like macroscopic shapes and with different microscopic textures, it emerges as an interesting material within tissue engineering. We have developed a protocol employing simultaneous CARS and SHG microscopy for monitoring the cellulose network characteristics and its impact on the integration of smooth muscle cells (SMCs) for functionalized artificial tissues. CARS and SHG overlay images of the cells and the cellulose fibers reveal an immediate interaction irrespective of scaffold morphology and that the SMCs attach to the cellulose fibers already during the first cultivation day without cell-adhesive coatings. During the subsequent 28 days, SMCs were found to readily proliferate and differentiate on the cellulose scaffold without the need for exogenous growth factors. However, the efficiency with which this occurred depended on the topography of the cellulose constructs, benefited by porous and less compact matrices. This brings forward the need for in-depth studies on how the microstructure of tissue scaffolds influences and can be optimized for native cell integration and proliferation, studies where the benefits of multi-modal non-linear microscopy can be fully exploited. © 2010 Copyright SPIE - The International Society for Optical Engineering.
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| 8. |
- Enejder, Annika, 1969, et al.
(författare)
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CARS microscopy of Alzheimer's diseased brain tissue
- 2014
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Ingår i: Progress in Biomedical Optics and Imaging - Proceedings of SPIE. - : SPIE. - 1605-7422. ; 8948
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Konferensbidrag (refereegranskat)abstract
- Alzheimera's disease (AD) is a progressive neurodegenerative disorder currently without cure, characterized by the presence of extracellular plaques surrounded by dystrophic neurites. In an effort to understand the underlying mechanisms, biochemical analysis (protein immunoblot) of plaque extracts reveals that they consist of amyloid-beta (Aβ) peptides assembled as oligomers, protofibrils and aggregates. Their spatial distribution has been confirmed by Thioflavin-S or immuno-staining with fluorescence microscopy. However, it is increasingly understood that the protein aggregation is only one of several mechanism that causes neuronal dysfunction and death. This raises the need for a more complete biochemical analysis. In this study, we have complemented 2-photon fluorescence microscopy of Thioflavin-S and Aβ immuno-stained human AD plaques with CARS microscopy. We show that the chemical build-up of AD plaques is more complex and that Aβ staining does not provide the complete picture of the spatial distribution or the molecular composition of AD plaques. CARS images provide important complementary information to that obtained by fluorescence microscopy, motivating a broader introduction of CARS microscopy in the AD research field.
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| 9. |
- Enejder, Annika, 1969, et al.
(författare)
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Chemical release from single PMMA microparticles monitored by CARS microscopy
- 2011
-
Ingår i: Progress in Biomedical Optics and Imaging - Proceedings of SPIE. Multiphoton Microscopy in the Biomedical Sciences XI; San Francisco, CA; 23-25 January 2011. - : SPIE. - 1605-7422. - 9780819484406 ; 7903
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Microparticles loaded with antigens, proteins, DNA, fungicides, and other functional agents emerge as ideal vehicles for vaccine, drug delivery, genetic therapy, surface- and crop protection. The microscopic size of the particles and their collective large specific surface area enables highly active and localized release of the functional substance. In order to develop designs with release profiles optimized for the specific application, it is desirable to map the distribution of the active substance within the particle and how parameters such as size, material and morphology affect release rates at single particle level. Current imaging techniques are limited in resolution, sensitivity, image acquisition time, or sample treatment, excluding dynamic studies of active agents in microparticles. Here, we demonstrate that the combination of CARS and THG microscopy can successfully be used, by mapping the spatial distribution and release rates of the fungicide and food preservative IPBC from different designs of PMMA microparticles at single-particle level. By fitting a radial diffusion model to the experimental data, single particle diffusion coefficients can be determined. We show that release rates are highly dependent on the size and morphology of the particles. Hence, CARS and THG microscopy provides adequate sensitivity and spatial resolution for quantitative studies on how single-particle properties affect the diffusion of active agents at microscopic level. This will aid the design of innovative microencapsulating systems for controlled release.
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| 10. |
- Enejder, Annika, 1969, et al.
(författare)
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Neuronal cell growth on polymeric scaffolds studied by CARS microscopy
- 2012
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Ingår i: Proceedings of SPIE - Multiphoton Microscopy in the Biomedical Sciences XII, San Francisco, CA, 22-24 January 2012. - : SPIE. - 1605-7422. - 9780819488695 ; 8226
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Konferensbidrag (refereegranskat)abstract
- For studies of neuronal cell integration and neurite outgrowth in polymeric scaffold materials as a future alternative for the treatment of damages in the neuronal system, we have developed a protocol employing CARS microscopy for imaging of neuronal networks. The benefits of CARS microscopy come here to their best use; (i) the overall three-dimensional (3D) arrangement of multiple cells and their neurites can be visualized without the need for chemical preparations or physical sectioning, potentially affecting the architecture of the soft, fragile scaffolds and (ii) details on the interaction between single cells and scaffold fibrils can be investigated by close-up images at sub-micron resolution. The establishment of biologically more relevant 3D neuronal networks in a soft hydrogel composed of native Extra Cellular Matrix (ECM) components was compared with conventional two-dimensional networks grown on a stiff substrate. Images of cells in the hydrogel scaffold reveal significantly different networking characteristics compared to the 2D networks, raising the question whether the functionality of neurons grown as layers in conventional cultivation dishes represents that of neurons in the central and peripheral nervous systems.
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| 11. |
- Enejder, Annika, 1969, et al.
(författare)
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Nonlinear nearfield microscopy
- 2013
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Ingår i: Progress in Biomedical Optics and Imaging - Proceedings of SPIE. - : SPIE. - 1605-7422. - 9780819493576 ; 8588
-
Konferensbidrag (refereegranskat)abstract
- Higher-order nonlinearity of light-matter interactions, such as second and third harmonic generation (SHG & THG) and Coherent anti-Stokes Raman Scattering (CARS) can be used for improving spatial resolution in microscopy as a consequence of the confinement of the nonlinear polarization to the high-intensity region of the focal volume. However, the resolution is limited to similar to 300 nm, not sufficient to resolve macromolecules or nanostructures of interest in the bio-, life- and nano-sciences. In the strive to push the resolution beyond the diffraction limit, allowing for nanoscale imaging, we have equipped a nonlinear optical microscope with a scanning-probe setup operated in tapping-mode feedback. A tapered, gold-coated, open-aperture tip with an aperture diameter of similar to 150 nm is scanned over the sample, probing the nonlinear nearfield generated by free-beam excitation. First nonlinear coherent Raman nearfield images of biological macromolecules and metallic nanostructures are shown. Limitations and future challenges with nonlinear nearfield microscopy are discussed.
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| 12. |
- Molin, Jesper, 1987, et al.
(författare)
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Feature-enhancing zoom to facilitate Ki-67 hot spot detection
- 2014
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Ingår i: Progress in Biomedical Optics and Imaging - Proceedings of SPIE. - : SPIE. - 1605-7422. - 9780819498342 ; 9041
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Konferensbidrag (refereegranskat)abstract
- Image processing algorithms in pathology commonly include automated decision points such as classifications. While this enables efficient automation, there is also a risk that errors are induced. A different paradigm is to use image processing for enhancements without introducing explicit classifications. Such enhancements can help pathologists to increase efficiency without sacrificing accuracy. In our work, this paradigm has been applied to Ki-67 hot spot detection. Ki-67 scoring is a routine analysis to quantify the proliferation rate of tumor cells. Cell counting in the hot spot, the region of highest concentration of positive tumor cells, is a method increasingly used in clinical routine. An obstacle for this method is that while hot spot selection is a task suitable for low magnification, high magnification is needed to discern positive nuclei, thus the pathologist must perform many zooming operations. We propose to address this issue by an image processing method that increases the visibility of the positive nuclei at low magnification levels. This tool displays the modified version at low magnification, while gradually blending into the original image at high magnification. The tool was evaluated in a feasibility study with four pathologists targeting routine clinical use. In a task to compare hot spot concentrations, the average accuracy was 75±4.1% using the tool and 69±4.6% without it (n=4). Feedback on the system, gathered from an observer study, indicate that the pathologists found the tool useful and fitting in their existing diagnostic process. The pathologists judged the tool to be feasible for implementation in clinical routine.
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| 13. |
- Qaiser, Mahmood, 1981, et al.
(författare)
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A fully automatic unsupervised segmentation framework for the brain tissues in MR images
- 2014
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Ingår i: Progress in Biomedical Optics and Imaging - Proceedings of SPIE. - : SPIE. - 1605-7422. - 9780819498311 ; 9038
-
Konferensbidrag (refereegranskat)abstract
- This paper presents a novel fully automatic unsupervised framework for the segmentation of brain tissues in magnetic resonance (MR) images. The framework is a combination of our proposed Bayesian-based adaptive mean shift (BAMS), a priori spatial tissue probability maps and fuzzy c-means. BAMS is applied to cluster the tissues in the joint spatialintensity feature space and then a fuzzy c-means algorithm is employed with initialization by a priori spatial tissue probability maps to assign the clusters into three tissue types; white matter (WM), gray matter (GM) and cerebrospinal fluid (CSF). The proposed framework is validated on multimodal synthetic as well as on real T1-weighted MR data with varying noise characteristics and spatial intensity inhomogeneity. The performance of the proposed framework is evaluated relative to our previous method BAMS and other existing adaptive mean shift framework. Both of these are based on the mode pruning and voxel weighted k-means algorithm for classifying the clusters into WM, GM and CSF tissue. The experimental results demonstrate the robustness of the proposed framework to noise and spatial intensity inhomogeneity, and that it exhibits a higher degree of segmentation accuracy in segmenting both synthetic and real MR data compared to competing methods.
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| 14. |
- Shirvany, Yazdan, 1980, et al.
(författare)
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Influence of Different Sources of Noise on Epileptic Spike EEG Source Localization
- 2013
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Ingår i: Progress in Biomedical Optics and Imaging - Proceedings of SPIE. - : SPIE. - 1605-7422. - 9780819494467 ; 8672
-
Konferensbidrag (refereegranskat)abstract
- Spike EEG source localization results are influenced by different errors and approximations, e.g., head-model complexity, EEG signal noise, electrode misplacements, tissue anisotropy, tissue conductivity noise as well as numerical errors. For accurate source localization, understanding the affects of these errors on the source localization is very crucial. Six finite element head models are selected for a head-model complexity study. A reference head model is used to create the synthetic EEG signals by placing a dipole inside the model to mimic the epileptic spike activity. To understand the influence of EEG signal noise, tissue conductivity noise and electrode misplacements on the EEG source localization, different level of noises are added to EEG signals, tissue conductivities and electrode positions, independently. To investigate the influence of white matter anisotropy, a realistic head model generated from T1-weighted MRI is used and the conductivity anisotropy for the white matter is calculated from diffusion tensor imaging (DTI). Major findings of the study include (1) the CSF layer plays an important role to achieve an accurate source localization result, (2) the source localization is very sensitive to the tissue conductivity noises, (3) one centimeter electrode misplacement cause approximately 8 mm localization error, (4) the source localization is robust with respect to the EEG signal noise and (5) the model with white matter anisotropy has small source localization error but large amplitude and orientation errors compared to the isotropic head model.
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| 15. |
- Sund, Patrik, et al.
(författare)
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The effect of fixed eye adaptation when using displays with a high luminance range
- 2012
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Ingår i: Progress in Biomedical Optics and Imaging - Proceedings of SPIE. - : SPIE. - 1605-7422. ; 8318
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Calibration of medical review displays according to the part 14 Grayscale Standard Display Function (GSDF) is important in order to obtain consistency in displayed image quality since display technology and viewing conditions may vary substantially. Unfortunately, the purpose of the GSDF calibration is best suited for low luminance range conditions but is not optimal when using modern displays with a high luminance range. Low contrast objects will then obtain a greater visibility in mid-gray areas compared to similar objects in bright or dark regions. In this study, low contrast sinusoidal patterns were displayed on a high luminance range monitor under realistic viewing conditions. In order to simulate the viewing of an x-ray image with both dark and bright regions displayed simultaneously, the luminance of the patterns ranged from 2 to 600 cd/m2 while the observers were always adapted to the logarithmic average of 35 cd/m2. The results show a clear relationship between the patterns deviation from the adaptation luminance level and the necessary contrast required to detect the pattern. The results also indicate the potential for an improvement in the lowcontrast detectability over a large luminance range by adjusting the GSDF for the limited eye adaptation.
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| 16. |
- Svalkvist, Angelica, et al.
(författare)
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Comparison of different approaches of estimating effective dose from reported exposure data in 3D imaging with interventional fluoroscopy systems
- 2014
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Ingår i: SPIE Medical Imaging 2014, 15-20 February 2014, San Diego, California, USA. Progress in Biomedical Optics and Imaging - Proceedings of SPIE. - : SPIE. - 1605-7422. ; 9033
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Three-dimensional (3D) imaging with interventional fluoroscopy systems is today a common examination. The examination includes acquisition of two-dimensional projection images, used to reconstruct section images of the patient. The aim of the present study was to investigate the difference in resulting effective dose obtained using different levels of complexity in calculations of effective doses from these examinations. In the study the Siemens Artis Zeego interventional fluoroscopy system (Siemens Medical Solutions, Erlangen, Germany) was used. Images of anthropomorphic chest and pelvis phantoms were acquired. The exposure values obtained were used to calculate the resulting effective doses from the examinations, using the computer software PCXMC (STUK, Helsinki, Finland). The dose calculations were performed using three different methods: 1. using individual exposure values for each projection image, 2. using the mean tube voltage and the total DAP value, evenly distributed over the projection images, and 3. using the mean kV and the total DAP value, evenly distributed over smaller selection of projection images. The results revealed that the difference in resulting effective dose between the first two methods was smaller than 5%. When only a selection of projection images were used in the dose calculations the difference increased to over 10%. Given the uncertainties associated with the effective dose concept, the results indicate that dose calculations based on average exposure values distributed over a smaller selection of projection angles can provide reasonably accurate estimations of the radiation doses from 3D imaging using interventional fluoroscopy systems. © 2014 SPIE.
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| 17. |
- Svalkvist, Angelica, et al.
(författare)
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Investigation of the effect of varying scatter-to-primary ratios on nodule contrast in chest tomosynthesis
- 2011
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Ingår i: Medical Imaging 2011. - : SPIE - International Society for Optical Engineering. - 9780819485038 ; 7961
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The primary aim of the present work was to analyze the effects of varying scatter-to-primary ratios on the appearance of simulated nodules in chest tomosynthesis section images. Monte Carlo simulations of the chest tomosynthesis system GE Definium 8000 VolumeRAD (GE Healthcare, Chalfont St. Giles, UK) were used to investigate the variation of scatter-to-primary ratios between different angular projections. The simulations were based on a voxel phantom created from CT images of an anthropomorphic chest phantom. An artificial nodule was inserted at 80 different positions in the simulated phantom images, using five different approaches for the scatter-to-primary ratios in the insertion process. One approach included individual determination of the scatter-to primary-ratio for each projection image and nodule location, while the other four approaches were using mean value, median value and zero degree projection value of the scatter-to-primary ratios at each nodule position as well as using a constant scatter-to-primary ratio of 0.5 for all nodule positions. The results indicate that the scatter-to-primary ratios vary up to a factor of 10 between the different angular tomosynthesis projections (±15°). However, the error in the resulting nodule contrast introduced by not taking all variations into account is in general smaller than 10 %.
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| 18. |
- Thompson, Alex, et al.
(författare)
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Hyperspectral fluorescence lifetime fibre probe spectroscopy for use in the study and diagnosis of osteoarthritis and skin cancer
- 2011
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Ingår i: Optical Biopsy IX. - : SPIE. - 1605-7422. - 9780819484321 ; 7895
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Konferensbidrag (refereegranskat)abstract
- We present the application of two fibre-optic-coupled time-resolved spectrofluorometers and a compact steady-state diffuse reflected light/fluorescence spectrometer to in vivo and ex vivo studies of skin cancer and osteoarthritis. In a clinical study of skin cancer, 27 lesions on 25 patients were investigated in vivo before surgical excision of the region measured. Preliminary analysis reveals a statistically significant decrease in the autofluorescence lifetime of basal cell carcinomas compared to neighbouring healthy tissue. A study of autofluorescence signals associated with the onset of osteoarthritis indicates autofluorescence lifetime changes associated with collagen degradation.
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