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Biomedical subjects

Mikael Karlsson

Publications and source records attributed to Mikael Karlsson.

At least 19 recordsLinked to original sources
PubMed2006

1-[11C]-acetate PET imaging in head and neck cancer--a comparison with 18F-FDG-PET: implications for staging and radiotherapy planning.

PURPOSE: The aim of this study was to evaluate the feasibility of using 1-[(11)C]-acetate positron emission tomography (ACE-PET) to detect and delineate the gross tumour volume of head and neck cancer before radiotherapy, and to compare the results with those obtained using (18)F-fluoro-2-deoxy-D: -glucose (FDG) PET. METHODS: Ten patients with histologically verified squamous cell carcinoma were investigated by FDG-PET and dynamic ACE-PET prior to radiotherapy. The two scans were performed on the same day or on consecutive days, except in one patient in whom they were done 5 days apart. Diagnostic CT or MRI was performed in all patients. The image data sets were analysed both visually and semi-quantitatively. All primary tumours and metastases were delineated automatically by using the 50% threshold of maximum radioactivity corrected for background. The mean standardised uptake value (SUV) and the tumour volumes were evaluated and compared. RESULTS: All ten primary tumours were detected by ACE-PET, while nine primaries were detected by FDG-PET and CT and/or MRI. The ACE SUV tended to be lower than the FDG SUV (5.3+/-2.7 vs 9.6+/-7.0, p=0.07). The tumour volumes delineated with ACE were on average 51% larger than the FDG volumes (p<0.05). ACE-PET identified 20/21 lymph node metastases, while only 13/21 lesions were detected by FDG-PET and 16/21 lesions by CT or MRI. CONCLUSION: ACE-PET appears promising for the staging of head and neck cancer. The biological information provided by both FDG and ACE must be carefully validated before it can be used in clinical routine for radiation treatment planning. More studies are needed to evaluate the differences in volumes and to confirm the clinical potential of both FDG and ACE-PET, especially in radiotherapy.

Acetates↗
PubMed2006

Pencil kernel correction and residual error estimation for quality-index-based dose calculations.

Experimental data from 593 photon beams were used to quantify the errors in dose calculations using a previously published pencil kernel model. A correction of the kernel was derived in order to remove the observed systematic errors. The remaining residual error for individual beams was modelled through uncertainty associated with the kernel model. The methods were tested against an independent set of measurements. No significant systematic error was observed in the calculations using the derived correction of the kernel and the remaining random errors were found to be adequately predicted by the proposed method.

Biophysical Phenomena↗
PubMed2006

Photon pencil kernel parameterisation based on beam quality index.

BACKGROUND AND PURPOSE: New treatment techniques in radiotherapy employ increasing dose calculation complexity in treatment planning. For an adequate check of the results coming from a modern treatment planning system, clinical tools with almost the same degree of generality and accuracy as the planning system itself are needed. To fulfil this need we propose a photon pencil kernel parameterization based on a minimum of input data that can be used for phantom scatter calculations. Through scatter integration the pencil kernel model can calculate common parameters, such as TPR or phantom scatter factors, used in various dosimetric QA (quality assurance) procedures. MATERIAL AND METHODS: The proposed model originates from an already published radially parameterized pencil kernel. A depth parameterization of the pencil kernel parameters has been introduced, based on a large database containing commissioned beam data for a commercial treatment planning system. The entire pencil kernel model demands only one photon beam quality index, TPR20,10, as input. RESULTS: By comparing the dose calculation results to the extensive experimental data set in the database, it has been possible to make a thorough analysis of the resulting accuracy. The errors in calculated doses, normalized to the reference geometry, are in most cases smaller than 2%. CONCLUSIONS: The investigation shows that a pencil kernel model based only on TPR20,10 can be used for dosimetric verification purposes in megavoltage photon beams at depths below the range of contaminating electrons.

Algorithms↗
PubMed2006

"Distributed proton radiation therapy"--a new concept for advanced competence support.

The increased interest in high precision radiation therapy is to a large extent driven by the potential of modern imaging technology. The aim of this project was to analyse how an expensive proton facility best could support a multi-centre health care system. We have developed a model for distributed expert collaboration where all clinical experts will work close to their patients in regional centres. Patients who are candidates for proton therapy will be examined and dose-planned at their regional clinic, discussed in a fully information supported video conference and digitally made available at the proton treatment facility. The proton facility itself will be placed near a communication centre easily reached by all patients where they will be treated under full responsibility of their own physician at the home clinic. This concept has been analysed in detail both with respect to the overall functionality and with respect to possible weaknesses. It was found that the concept of distributed radiation therapy, as proposed here, will offer a stable clinical solution for advanced radiation therapy. It will support the spread of knowledge, serve as a fully developed backup system and the concept will further serve as an efficient base for clinical research.

Ambulatory Care Facilities↗
PubMed2006

Evaluation of uncertainty predictions and dose output for model-based dose calculations for megavoltage photon beams.

In many radiotherapy clinics an independent verification of the number of monitor units (MU) used to deliver the prescribed dose to the target volume is performed prior to the treatment start. Traditionally this has been done by using methods mainly based on empirical factors which, at least to some extent, try to separate the influence from input parameters such as field size, depth, distance, etc. The growing complexity of modern treatment techniques does however make this approach increasingly difficult, both in terms of practical application and in terms of the reliability of the results. In the present work the performance of a model-based approach, describing the influence from different input parameters through actual modeling of the physical effects, has been investigated in detail. The investigated model is based on two components related to megavoltage photon beams; one describing the exiting energy fluence per delivered MU, and a second component describing the dose deposition through a pencil kernel algorithm solely based on a measured beam quality index. Together with the output calculations, the basis of a method aiming to predict the inherent calculation uncertainties in individual treatment setups has been developed. This has all emerged from the intention of creating a clinical dose/MU verification tool that requires an absolute minimum of commissioned input data. This evaluation was focused on irregular field shapes and performed through comparison with output factors measured at 5, 10, and 20 cm depth in ten multileaf collimated fields on four different linear accelerators with varying multileaf collimator designs. The measurements were performed both in air and in water and the results of the two components of the model were evaluated separately and combined. When compared with the corresponding measurements the resulting deviations in the calculated output factors were in most cases smaller than 1% and in all cases smaller than 1.7%. The distribution describing the calculation errors in the total dose output has a mean value of -0.04% and a standard deviation of 0.47%. In the dose calculations a previously developed correction of the pencil kernel was applied that managed to contract the error distribution considerably. A detailed analysis of the predicted uncertainties versus the observed deviations suggests that the predictions indeed can be used as a basis for creating action levels and tracking dose calculation errors in homogeneous media.

Air↗
PubMed2006

Dose uncertainties in photon pencil kernel calculations at off-axis positions.

The purpose of this study was to investigate the specific problems associated with photon dose calculations in points located at a distance from the central beam axis. These problems are related to laterally inhomogeneous energy fluence distributions and spectral variations causing a lateral shift in the beam quality, commonly referred to as off-axis softening (OAS). We have examined how the dose calculation accuracy is affected when enabling and disabling explicit modeling of these two effects. The calculations were performed using a pencil kernel dose calculation algorithm that facilitates modeling of OAS through laterally varying kernel properties. Together with a multi-source model that provides the lateral energy fluence distribution this generates the total dose output, i.e., the dose per monitor unit, at an arbitrary point of interest. The dose calculation accuracy was evaluated through comparisons with 264 measured output factors acquired at 5, 10, and 20 cm depth in four different megavoltage photon beams. The measurements were performed up to 18 cm from the central beam axis, inside square fields of varying size and position. The results show that calculations including explicit modeling of OAS were considerably more accurate, up to 4%, than those ignoring the lateral beam quality shift. The deviations caused by simplified head scatter modeling were smaller, but near the field edges additional errors close to 1% occurred. When enabling full physics modeling in the dose calculations the deviations display a mean value of -0.1%, a standard deviation of 0.7%, and a maximum deviation of -2.2%. Finally, the results were analyzed in order to quantify and model the inherent uncertainties that are present when leaving the central beam axis. The off-axis uncertainty component showed to increase with both off-axis distance and depth, reaching 1% (1 standard deviation) at 20 cm depth.

Algorithms↗
PubMed2005

Science and norms in policies for sustainable development: assessing and managing risks of chemical substances and genetically modified organisms in the European Union.

Use of chemical substances and genetically modified organisms cause complex problems characterised by scientific uncertainty and controversies. Aiming at sustainable development, policies for assessment, and management of risks in the two areas are under development in the European Union. The article points out that both science and norms play a central role in risk assessment as well as risk management and suggests that the precautionary principle, the principle of public participation, and the polluter pays principle, all adopted in the European Union, offer a way to operationalise the concept of sustainable development. It is shown, however, that a number of steps ought to be taken to better implement the principles through different policy measures. In doing so, and by recognising the role of both science and norms, the decision-making on risks related to the use of chemicals or genetically modified organisms can be improved to better promote sustainable development.

Chemical Industry↗
PubMed2005

Conversion of polarographic electrode measurements--a computer based approach.

The polarographic measurement of tissue oxygenation is one of the most widely used methods in clinical practice for the quantification of tumour hypoxia. However, due to the particular features of the electrode measuring process, the results of the measurements do not accurately reflect the tumour oxygenation. This study aimed to find a correlation between the electrode measurements and the tumour oxygenation in an attempt to improve the accuracy of the predictions regarding the response to treatment based on electrode measurements. A previously developed computer model that allows the simulation of tumour tissue and electrode measurements was used. The oxygenation of a large number of tumours with biologically relevant distributions of blood vessels was theoretically calculated. Simulations of electrode measurements allowed the comparison between the real tissue oxygenation and the results obtained with the electrode. A semi-empirical relationship between the hypoxic fraction measured by the electrode and the real hypoxic fraction in the tissue has been found. The impact of the correction of the electrode measurements in terms of predictions for tumour control probability was estimated for a few clinical examples. The range of possible true values corresponding to one measurement has also proven useful for explaining the apparently unexpected response to the treatment of some patients. The corrected hypoxic fraction which is believed to be closer to the real value of tissue hypoxia predicts much smaller control probabilities than the raw electrode measurements. This could provide an explanation for the apparently unexpected failure to respond to the treatment of some of the patients with apparently favourable tumour oxygenation. This also means that the electrode measurements cannot be used directly for the quantitative modelling of tumour response to the treatment. The conversion method proposed in this paper might however strengthen the statistical power of the correlations between the electrode measurements and the treatment outcome.

Animals↗
PubMed2005

Effects on electron beam penumbra using the photon MLC to reduce bremsstrahlung leakage for an add-on electron MLC.

Electron IMRT treatments have the potential to reduce the integral dose due to the limited range of the electrons. However, bremsstrahlung produced in the scattering foils could penetrate an added electron MLC (eMLC), thus producing an unmodulated dose contribution that could become unacceptable in electron IMRT treatments. To limit this bremsstrahlung contribution, the photon MLC (xMLC) was used to track the eMLC, but with a margin to avoid penumbra widening through partial screening of the effective electron source. The purpose of this work was to study the effect of the photon-electron MLC tracking on the electron beam penumbra for different treatment head designs. Both isocentric designs and designs where the eMLC is used close to the patient (proximity geometry) have been analysed using Monte Carlo simulations. At 22.5 MeV energy, a tracking margin of 1 cm was enough to avoid penumbra degradation for a helium-filled isocentric geometry, while air-filled geometries (including proximity geometries) require a 2-3 cm margin. Illustrated by an example of a chest wall treatment by electron IMRT, the use of 1 cm tracking margin will reduce the collimator leakage contribution by a factor of 36 as compared to using a static setting of the photon collimator.

Electrons↗
PubMed2005

Does electron and proton therapy reduce the risk of radiation induced cancer after spinal irradiation for childhood medulloblastoma? A comparative treatment planning study.

The aim of this treatment planning comparison study was to explore different spinal irradiation techniques with respect to the risk of late side-effects, particularly radiation-induced cancer. The radiotherapy techniques compared were conventional photon therapy, intensity modulated x-ray therapy (IMXT), conventional electron therapy, intensity/energy modulated electron therapy (IMET) and proton therapy (IMPT).CT images for radiotherapy use from five children, median age 8 and diagnosed with medulloblastoma, were selected for this study. Target volumes and organs at risk were defined in 3-D. Treatment plans using conventional photon therapy, IMXT, conventional electron therapy, IMET and IMPT were set up. The probability of normal tissue complication (NTCP) and the risk of cancer induction were calculated using models with parameters-sets taken from published data for the general population; dose data were taken from dose volume histograms (DVH). Similar dose distributions in the targets were achieved with all techniques but the absorbed doses in the organs-at-risk varied significantly between the different techniques. The NTCP models based on available data predicted very low probabilities for side-effects in all cases. However, the effective mean doses outside the target volumes, and thus the predicted risk of cancer induction, varied significantly between the techniques. The highest lifetime risk of secondary cancers was estimated for IMXT (30%). The lowest risk was found with IMPT (4%). The risks associated with conventional photon therapy, electron therapy and IMET were 20%, 21% and 15%, respectively. This model study shows that spinal irradiation of young children with photon and electron techniques results in a substantial risk of radiation-induced secondary cancers. Multiple beam IMXT seems to be associated with a particularly high risk of secondary cancer induction. To minimise this risk, IMPT should be the treatment of choice. If proton therapy is not available, advanced electron therapy may provide a better alternative.

Child↗
PubMed2005

The effects of hypoxia on the theoretical modelling of tumour control probability.

Theoretical modelling of tumour response is increasingly used for the prediction of treatment result and has even been proposed as ranking criteria in some algorithms for treatment planning. Tumour response to radiation is greatly influenced by the details of tumour microenvironment, especially hypoxia, that unfortunately are not always taken into consideration for these simulations. This paper intends to investigate the effects of various assumptions regarding hypoxia distribution in tumours on the predictions of treatment outcome. A previously developed model for simulating theoretically the oxygenation in biologically relevant tissues, including results from oxygen diffusion, consumption and perfusion limitations in tumours, was used to investigate the effects of the different aspects of hypoxia on the predictions of treatment outcome. Thus, both the continuous distribution of values and the temporal variation of hypoxia patterns were taken into consideration and were compared with a 'black-and-white' simplification with a fully hypoxic compartment and a fully oxic one. It was found that the full distribution of oxygenation in the tissue is needed for accurate results. The 'black-and-white' simplification, while showing the same general trends for the predictions of radiation response, could lead to serious over-estimations of the tumour control probability. It was also found that the presence of some hypoxia for every treatment fraction leads to a decrease in the predicted local control, regardless of the change of the hypoxic pattern throughout the duration of the whole treatment. The results thus suggest that the assumptions regarding tumour hypoxia influence very much the predictions of treatment outcome and therefore they have to be very carefully incorporated into the theoretical modelling.

Cell Hypoxia↗
PubMed2005

Number of patients potentially eligible for proton therapy.

A group of Swedish radiation oncologists and hospital physicists have estimated the number of patients in Sweden suitable for proton beam therapy in a facility where one of the principal aims is to facilitate randomized and other studies in which the advantage of protons can be shown and the magnitude of the differences compared with optimally administered conventional radiation treatment, also including intensity-modulated radiation therapy (IMRT) and brachytherapy, can be shown. The estimations have been based on current statistics of tumour incidence in Sweden, number of patients potentially eligible for radiation treatment, scientific support from clinical trials and model dose planning studies and knowledge of the dose-response relations of different tumours together with information on normal tissue complication rates. In Sweden, it is assessed that between 2200 and 2500 patients annually are eligible for proton beam therapy, and that for these patients the potential therapeutic benefit is so great as to justify the additional expense of proton therapy. This constitutes between 14-15% of all irradiated patients annually.

Dose-Response Relationship, Radiation↗
PubMed2005

The use of risk estimation models for the induction of secondary cancers following radiotherapy.

Theoretical predictions of cancer risk from radiotherapy may be used as a complementary criterion for the selection of successful treatment plans together with the classical approach of estimating the possible deterministic effects. However, any such attempts must take into consideration the specific features of radiation treatment. This paper explores several possible methods for estimating the risk of cancer following radiotherapy in order to investigate the influences of the fractionation and the non-uniformity of the dose to the irradiated organ. The results indicate that dose inhomogeneity plays an important role in predicting the risk for secondary cancer and therefore for predictive purposes it must be taken into account through the use of the dose volume histograms. They also suggest that the competition between cell killing and the induction of carcinogenic mutations has to be taken into consideration for more realistic risk estimations. Furthermore, more realistic parameters could be obtained if this competition is also included in analyses of epidemiological data from radiotherapy applications.

Dose-Response Relationship, Radiation↗
PubMed2005

Photon and electron collimator effects on electron output and abutting segments in energy modulated electron therapy.

In energy modulated electron therapy a large fraction of the segments will be arranged as abutting segments where inhomogeneities in segment matching regions must be kept as small as possible. Furthermore, the output variation between different segments should be minimized and must in all cases be well predicted. For electron therapy with add-on collimators, both the electron MLC (eMLC) and the photon MLC (xMLC) contribute to these effects when an xMLC tracking technique is utilized to reduce the x-ray induced leakage. Two add-on electron collimator geometries have been analyzed using Monte Carlo simulations: One isocentric eMLC geometry with an isocentric clearance of 35 cm and air or helium in the treatment head, and one conventional proximity geometry with a clearance of 5 cm and air in the treatment head. The electron fluence output for 22.5 MeV electrons is not significantly affected by the xMLC if the shielding margins are larger than 2-3 cm. For small field sizes and 9.6 MeV electrons, the isocentric design with helium in the treatment head or shielding margins larger than 3 cm is needed to avoid a reduced electron output. Dose inhomogeneity in the matching region of electron segments is, in general, small when collimator positions are adjusted to account for divergence in the field. The effect of xMLC tracking on the electron output can be made negligible while still obtaining a substantially reduced x-ray leakage contribution. Collimator scattering effects do not interfere significantly when abutting beam techniques are properly applied.

Artifacts↗
PubMed2004

A practical method to calculate head scatter factors in wedged rectangular and irregular MLC shaped beams for external and internal wedges.

Factor based methods for absorbed dose or monitor unit calculations are often based on separate data sets for open and wedged beams. The determination of basic beam parameters can be rather time consuming, unless equivalent square methods are applied. When considering irregular wedged beams shaped with a multileaf collimator, parametrization methods for dosimetric quantities, e.g. output ratios or wedge factors as a function of field size and shape, become even more important. A practical method is presented to derive wedged output ratios in air (S(c,w)) for any rectangular field and for any irregular MLC shaped beam. This method was based on open field output ratios in air (S(c)) for a field with the same collimator setting, and a relation f(w) between S(c,w) and S(c). The relation f(w) can be determined from measured output ratios in air for a few open and wedged fields including the maximum wedged field size. The function f(w) and its parametrization were dependent on wedge angle and treatment head design, i.e. they were different for internal and external wedges. The proposed method was tested for rectangular wedged fields on three accelerators with internal wedges (GE, Elekta, BBC) and two accelerators with external wedges (Varian). For symmetric regular beams the average deviation between calculated and measured S(c,w) / S(c) ratios was 0.3% for external wedges and about 0.6% for internal wedges. Maximum deviations of 1.8% were obtained for elongated rectangular fields on the GE and ELEKTA linacs with an internal wedge. The same accuracy was achieved for irregular MLC shaped wedged beams on the accelerators with MLC and internal wedges (GE and Elekta), with an average deviation < 1% for the fields tested. The proposed method to determine output ratios in air for wedged beams from output ratios of open beams, combined with equivalent square approaches, can be easily integrated in empirical or semi-empirical methods for monitor unit calculations.

Algorithms↗
PubMed2004

The relationship between temporal variation of hypoxia, polarographic measurements and predictions of tumour response to radiation.

The polarographic oxygen sensor is one of the most used devices for in vivo measurements of oxygen and many other measurement techniques for measuring tumour hypoxia are correlated with electrode measurements. Little is known however about the relationship between electrode measurements and the real tissue oxygenation. This paper investigates the influence of the temporal change of the hypoxic pattern on the electrode measurements and the tumour response. Electrode measurements and tumour response were simulated using a computer program that allows both the calculation of the tissue oxygenation with respect to the two types of hypoxia that might arise in tumours and the virtual insertion of the electrode into the tissue. It was therefore possible to control the amount of each type of hypoxia in order to investigate their influence on the measurement results. Tissues with several vascular architectures ranging from well oxygenated to poorly oxygenated were taken into consideration as might be seen in practice. The influence of the electrode measurements on the treatment outcome was estimated by calculating the tumour control probability for the tumours characterized either by the real or by the measured tumour oxygenation. We have simulated electrode oxygen measurements in different types of tissues, covering a wide range of tumour oxygenations. The results of the simulations showed that the measured distribution depends on the details of the vascular network and not on the type of hypoxia. We have also simulated the effects of the temporal change of the acute hypoxic pattern due to the opening and the closure of different blood vessels during a full fractionated treatment. The results of this simulation suggested that the temporal variation of the hypoxic pattern does not lead to significantly different results for the electrode measurements or the predicted tumour control probabilities. In conclusion, it was found that the averaging effect of the electrode leads to a systematic deviation between the actual oxygen distribution and the measured distribution. However, as the electrode reflects the general trends of the tissue oxygenation it has the potential of being used for the general characterization of tumour hypoxia even if the actual type of hypoxia measured by the electrode cannot be determined. Indeed, the change in time of the acute hypoxic region does not compensate for the lack of oxygenation at a specific moment and therefore does not influence the polarographic oxygen measurements.

Cell Survival↗