| 1. |
- Björkman, Anders, et al.
(författare)
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Cortical sensory and motor response in a patient whose hand has been replanted: One-year follow up with functional magnetic resonance imaging
- 2007
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Ingår i: Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery. - : Informa UK Limited. - 1651-2073 .- 0284-4311. ; 41:2, s. 70-76
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Tidskriftsartikel (refereegranskat)abstract
- Functional magnetic resonance imaging (fMRI) was used to study how a replanted hand regained its cortical territory parallel to recovery. The cortical response to sensory stimulation shifts from an ipsilateral to a bilateral pattern, and then to a predominantly contralateral activation. The cortical response to motor stimulation was normal from the first investigation.
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| 2. |
- Denekamp, Juliana, et al.
(författare)
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Hyperfractionation as an effective way of overcoming radioresistance
- 1998
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Ingår i: International Journal of Radiation Oncology, Biology, Physics. - 0360-3016 .- 1879-355X. ; 42:4, s. 705-709
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To model the influence of hypoxic radioprotection in fractionated treatments over a range of fraction sizes. To determine whether there is a "therapeutic window" of dose per fraction where hypoxic radioresistance could be reduced, and if so, where it occurs in different cell lines. MATERIALS AND METHODS: A mathematical model has been used to simulate the response of cells to low doses of radiation, in the region of clinical interest. We have used the inducible repair variant of the linear quadratic (LQ) equation, with a hypersensitive region (alphaS) at low doses that gradually transforms to the accepted "resistance" in the shoulder region (alphaR). It contains two new parameters, the ratio alphaS/alphaR, and D(C). We have accepted that the "induction dose" D(C) is modified by anoxia to the same extent as the other parameters. We have initially modeled using theoretical parameters and then checked the conclusions with 14 sets of published experimental data for cell lines investigated for inducible repair. RESULTS: We have computed the clinical hypoxic protection (OER') as a function of dose per fraction in simulations of clinical fractionated schedules. We have identified a therapeutic window in terms of dose per fraction at about 0.5 Gy, where the OER' is minimized, regardless of the precise cell survival curve parameters. The minimum OER' varies from one cell line to another, falling to about 1.0 if alphaS/alphaR = 6-10 and even far below 1.0 if alphaS/alphaR > or = 20. DISCUSSION: Hyperfractionation using 0.5 Gy fractions may therefore be more effective than oxygen mimetic chemical sensitizers, since it could even make some tumor cells more sensitive than oxic normal tissues. The tumor lines that benefit most from this type of sensitization are those with the highest intrinsic oxic radioresistance, i.e. those with high SF2 values.
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| 4. |
- Denekamp, Juliana, et al.
(författare)
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Vasculature and microenvironmental gradients: the missing links in novel approaches to cancer therapy?
- 1998
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Ingår i: Advances in Enzyme Regulation. - 0065-2571 .- 1873-2437. ; 38:1, s. 281-299
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Tidskriftsartikel (refereegranskat)abstract
- This paper illustrates how the concept of the malignant cell per se as the prime and only target in cancer therapy may be erroneous. The micro-vasculature evoked to satisfy nutritional requirements of solid tumors, and the inadequacy of this nutrition for all tumor cells, provide novel targeting concepts. The vascular architecture and the microenvironmental gradients (VAMP) will differ from one tumor to another and may determine whether current therapies succeed or fail. Many agents have a different toxicity or mode of action at the pathophysiological oxygen tensions that prevail in solid tumors. This warrants more attention. The hypoxic cell or the immature proliferating endothelial cell may provide tumor specificity that is more general than, and greater than, that conferred by the process of malignant transformation. The poor vasculature of solid tumors is often regarded as a problem by the oncologist. It limits the access of cytotoxic drugs, monoclonal antibodies, cytokines, etc. It also leads to hypoxic radioresistance because of diffusion limited chronic hypoxia and perfusion limited intermittent hypoxia, resulting from transient vessel closure. However, it can also be seen as a potential target, since prolonged vessel occlusion can lead to an avalanche of cell death. Strategies to prevent further expansion of the vascular network (anti-angiogenesis) should stabilize tumors and prevent further growth. Vascular targeting, aiming to damage the microvascular function and cause occlusion, can lead to extensive cell death. The target may relate to the excessive proliferation of endothelial cells in tumors or to abnormal functional aspects, such as altered cell shape (influencing permeability) adhesiveness to leukocytes or steps in the coagulation cascade. These microvascular features and microenvironmental gradients, and the phenotypic consequences of them, have been relatively neglected. The altered milieu and inadequate neovasculature is a common feature of all types of solid tumor, whereas the genetic changes that can give rise to a malignancy are very variable, from tumor site to site and even within a site from individual to individual. It seems, therefore, that therapies that could be of widespread general applicability might more easily be found from the micro-environmental or anti-vascular approaches than from gene therapy targeted at specific oncogenes. This approach will require cross fertilisation between scientists from quite disparate backgrounds, whose paths seldom cross, and who may not read, or even scan, each other's literature. If the endothelium or the low oxygen tension in subsets of tumor cells are the key to successful cancer treatment in mice, there are considerable implications for screening methods in vitro and for predictive and prognostic tests made on homogenized tumor samples.
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| 6. |
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| 7. |
- Olsrud, Johan, et al.
(författare)
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A two-compartment gel phantom for optimization and quality assurance in clinical BOLD fMRI
- 2008
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Ingår i: Magnetic Resonance Imaging. - : Elsevier BV. - 1873-5894 .- 0730-725X. ; 26:2, s. 279-286
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Tidskriftsartikel (refereegranskat)abstract
- Clinical applications of blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) depend heavily on robust paradigms, imaging methods and analysis procedures. In this work, as a means to optimize and perform quality assurance of the entire imaging and analysis chain, a phantom that provides a well known and reproducible signal change similar to a block type fMRI experiment is presented. It consists of two gel compartments with slightly different T(2) that dynamically enter and leave the imaged volume. The homogeneous gel in combination with a cylindrical geometry results in a well-defined T(2) difference causing a signal difference between the two compartments in T(2)-weighted MR images. From time series data obtained with the phantom, maps of percent signal change (PSC) and t-values are calculated. As an example of image parameter optimisation, the phantom is demonstrated to be useful for accurate determination of the influence of echo time (TE) on BOLD fMRI results, taking the t-value as a measure of sensitivity. In addition, the phantom is proposed as a tool for quality assurance (QA) since reproducible time series and t-maps are obtained in a series of independent repeat experiments. The phantom is relatively simple to build and can therefore be used by any clinical fMRI center.
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| 8. |
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| 9. |
- Toma-Dasu, Iuliana, et al.
(författare)
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Theoretical simulation of oxygen tension measurement in the tissue using a microelectrode: II. Simulated measurements in tissues
- 2002
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Ingår i: Radiotherapy and Oncology. - 0167-8140 .- 1879-0887. ; 64:1, s. 109-118
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: The objectives of this study were to make a computer simulation of tissues with different vascular structures and to simulate measurements of oxygen tension using an Eppendorf-like electrode in these tissues and to compare the response to radiation of the tissues with the real oxygen distributions (called input distribution) with the response to radiation of the tissues in which the oxygen distribution is given by the results of the simulated measurements (called output distribution).MATERIALS AND METHODS: The structure of various tissues and the measurements of oxygen tension using a microelectrode were simulated using a computer program. The mathematical model used combines the description of a gradient of tissue oxygenation and the electrode absorption process.RESULTS: We have compared the oxygen distributions resulting from diffusion (input) with those obtained from a simulation of measurements (output) for various tissues in the same points. Because the electrode measurement is an averaging process, the calculated oxygen distributions are different from the expected ones and the extreme high and low values are not detected. We have then calculated the survival curves describing the response to radiation if there is a small fraction of truly hypoxic cells (expected values) or a large fraction of cells at intermediate values (observed results) in order to determine the differences between them.CONCLUSIONS: The results of our study show that oxygen electrode measurements do not give the true distribution of pO(2) values in the tissue. However, our results do not contradict the numerous empirical correlations between the Eppendorf measurements of tumour oxygenation and the outcome of treatments. Measurement results will be misleading for modelling purposes since they do not reflect the actual distributions of oxygen tensions in the measured tissue. Decisions based on such modelling could be very dangerous, especially with respect to the clinical response of tumours to new treatments.
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| 10. |
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| 11. |
- Toma-Dasu, Iuliana, et al.
(författare)
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Theoretical simulation of oxygen tension measurement in tissues using a microelectrode: I. The response function of the electrode
- 2001
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Ingår i: Physiological Measurement. - : IOP Publishing. - 0967-3334 .- 1361-6579. ; 22:4, s. 713-725
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this article is to determine the correlation between the actual oxygen distribution in tissues and the distribution of oxygen measured by microelectrodes. This correlation is determined by the response function of the electrode, which depends on the oxygen consumed by the electrode. In tissue it is necessary to consider the gradients resulting from cellular respiration. A computer program has been used to simulate the vascular structure of various tissues and also the measurements of oxygen tension using a polarographic electrode. The electrode absorption process is described using a theoretical model. The gradient of oxygen in tissue is described by a mathematical model that takes into consideration both diffusion and cellular consumption of oxygen. We have compared the results obtained using the response function of the electrode and some simplifications of it. The results of these comparisons show that there are some differences in the 'observed' distributions of the oxygen tension in tissues predicted using different formulae for the electrode response function. Also, there are considerable differences between the input oxygen distribution and the measured values in all cases. All the results of the simulations of the oxygen tension 'observed' by a 12 microm polarographic electrode, using different response functions of the electrode, show that the electrode averages the values from many cells. Care should be taken in using a simplification for the response function of the electrode, especially if the results are going to be used as input values in modelling the tumour response to new treatments and/or as a basis of selecting patients for treatments. A computer simulation of measurement of oxygen tensions in regions of steep pO2 gradients shows that extremely high and extremely low pO2 values will not be detected.
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| 12. |
- Waites, Anthony B, et al.
(författare)
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Flexible statistical modelling detects clinical functional magnetic resonance imaging activation in partially compliant subjects.
- 2007
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Ingår i: Magnetic Resonance Imaging. - : Elsevier BV. - 1873-5894 .- 0730-725X. ; 25:2, s. 188-196
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Tidskriftsartikel (refereegranskat)abstract
- Clinical functional magnetic resonance imaging (MRI) occasionally fails to detect significant activation, often due to variability in task performance. The present study seeks to test whether a more flexible statistical analysis can better detect activation, by accounting for variance associated with variable compliance to the task over time. Experimental results and simulated data both confirm that even at 80% compliance to the task, such a flexible model outperforms standard statistical analysis when assessed using the extent of activation (experimental data), goodness of fit (experimental data), and area under the operator characteristic curve (simulated data). Furthermore, retrospective examination of 14 clinical fMRI examinations reveals that in patients where the standard statistical approach yields activation, there is a measurable gain in model performance in adopting the flexible statistical model, with little or no penalty in lost sensitivity. This indicates that a flexible model should be considered, particularly for clinical patients who may have difficulty complying fully with the study task. (c) 2007 Elsevier Inc. All rights reserved.
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