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Biomedical subjects

B Warkentin

Publications and source records attributed to B Warkentin.

At least 19 recordsLinked to original sources
PubMed2005

Limitations of a TCP model incorporating population heterogeneity.

The variation between individuals in their dose-response characteristics complicates attempts to extract estimates of radiobiological parameters (e.g. alpha, beta, etc) from fits to clinical dose-response data. The use of 'population' dose-response models that explicitly account for this variability is necessary to avoid obtaining skewed parameter estimates. In this work, we evaluated an example of a 'population' tumour control probability (TCP) model in terms of its ability to provide reliable parameter estimates. This was accomplished by performing fits of this population model to 'pseudo' data sets, which were generated with Monte Carlo techniques and based on preset values for the various radiobiological parameters. The fitting exercises illustrated considerable correlations between the model parameters. Especially significant was the large correlation observed between the parameter mu=alpha/sigmaalpha used to characterize the level of population heterogeneity in radiosensitivity and the alpha/beta parameter typically used to describe the response to fractionation. The results imply that fits to clinical data may not be able to distinguish between tumours exhibiting a high degree of heterogeneity and a strong beta-mechanism and those containing little heterogeneity and having a weak beta-mechanism. One implication is that basing the design of optimal fractionation regimes on such fitting results may be error-prone. If in vitro assays are to be used to independently determine biologically reasonable ranges for parameter values, an accurate knowledge of the relationship between in vitro and in vivo dose-response characteristics is required.

Animals↗
PubMed2005

Radiation damage, repopulation and cell recovery analysis of in vitro tumour cell megacolony culture data using a non-Poissonian cell repopulation TCP model.

The effects of radiation damage, tumour repopulation and cell sublethal damage repair and the possibility of extracting information about the model parameters describing them are investigated in this work. Previously published data on two different cultured cell lines were analysed with the help of a tumour control probability (TCP) model that describes tumour cell dynamics properly. Different versions of a TCP model representing the cases of full or partial cell recovery between fractions of radiation, accompanied by repopulation or no repopulation were used to fit the data and were ranked according to statistical criteria. The data analysis shows the importance of the linear-quadratic mechanism of cell damage for the description of the in vitro cell dynamics. In a previous work where in vivo data were analysed, the employment of the single hit model of cell kill and cell repopulation produced the best fit, while ignoring the quadratic term of cell damage in the current analysis leads to poor fits. It is also concluded that more experiments using different fractionation regimes producing diverse data are needed to help model analysis and better ranking of the models.

Adenocarcinoma↗
PubMed2005

Three-dimensional IMRT verification with a flat-panel EPID.

A three-dimensional (3D) intensity-modulated radiotherapy (IMRT) pretreatment verification procedure has been developed based on the measurement of two-dimensional (2D) primary fluence profiles using an amorphous silicon flat-panel electronic portal imaging device (EPID). As described in our previous work, fluence profiles are extracted from EPID images by deconvolution with kernels that represent signal spread in the EPID due to radiation and optical scattering. The deconvolution kernels are derived using Monte Carlo simulations of dose deposition in the EPID and empirical fitting methods, for both 6 and 15 MV photon energies. In our new 3D verification technique, 2D fluence modulation profiles for each IMRT field in a treatment are used as input to a treatment planning system (TPS), which then generates 3D doses. Verification is accomplished by comparing this new EPID-based 3D dose distribution to the planned dose distribution calculated by the TPS. Thermoluminescent dosimeter (TLD) point dose measurements for an IMRT treatment of an anthropomorphic phantom were in good agreement with the EPID-based 3D doses; in contrast, the planned dose under-predicts the TLD measurement in a high-gradient region by approximately 16%. Similarly, large discrepancies between EPID-based and TPS doses were also evident in dose profiles of small fields incident on a water phantom. These results suggest that our 3D EPID-based method is effective in quantifying relevant uncertainties in the dose calculations of our TPS for IMRT treatments. For three clinical head and neck cancer IMRT treatment plans, our TPS was found to underestimate the mean EPID-based doses in the critical structures of the spinal cord and the parotids by approximately 4 Gy (11%-14%). According to radiobiological modeling calculations that were performed, such underestimates can potentially lead to clinically significant underpredictions of normal tissue complication rates.

Algorithms↗
PubMed2005

Investigating the effect of clonogen resensitization on the tumor response to fractionated external radiotherapy.

In this work we further develop the modeling of tumor dynamics by proposing a mechanism of tumor resensitization that is based on the process of reoxygenation. Reoxygenation is modeled using the concept of nonstationary diffusion of oxygen. This leads to the derivation of an explicit expression for the radiosensitivity parameter that predicts a radiosensitivity that increases with time. To account for the resensitization mechanism, the time-dependent expression for the radiosensitivity is then incorporated within a tumor control probability (TCP) model that already includes tumor cell repopulation and repair. We fit a set of experimental animal TCP curves corresponding to several different fractionation regimes using both the modified (with resensitization) and unmodified (without resensitization) versions of the TCP model. In comparison to the unmodified model, the modified model produces statistically superior fits, and is able to describe an "inverse" dose-fractionation behavior present in the data.

Animals↗
PubMed2003

Investigating the effect of cell repopulation on the tumor response to fractionated external radiotherapy.

In this work we study the descriptive power of the main tumor control probability (TCP) models based on the linear quadratic (LQ) mechanism of cell damage with cell recovery. The Poisson, binomial, and a dynamic TCP model, developed recently by Zaider and Minerbo are considered. The Zaider-Minerbo model takes cell repopulation into account. It is shown that the Poisson approximation incorporating cell repopulation is conceptually incorrect. Based on the Zaider-Minerbo model, an expression for the TCP for fractionated treatments with varying intervals between two consecutive fractions and with cell survival probability that changes from fraction to fraction is derived. The models are fitted to an experimental data set consisting of dose response curves that correspond to different fractionation regimes. The binomial TCP model based on the LQ mechanism of cell damage solely was unable to fit the fractionated response data. It was found that the Zaider-Minerbo model, which takes tumor cell repopulation into account, best fits the data.

Cell Proliferation↗
PubMed2003

Inverse treatment planning by physically constrained minimization of a biological objective function.

In the current state-of-the art of clinical inverse planning, the design of clinically acceptable IMRT plans is predominantly based on the optimization of physical rather than biological objective functions. A major impetus for this trend is the unproven predictive power of radiobiological models, which is largely due to the scarcity of data sets for an accurate evaluation of the model parameters. On the other hand, these models do capture the currently known dose-volume effects in tissue dose-response, which should be accounted for in the process of optimization. In order to incorporate radiobiological information in clinical treatment planning optimization, we propose a hybrid physico-biological approach to inverse treatment planning based on the application of a continuous penalty function method to the constrained minimization of a biological objective. The objective is defined as the weighted sum of normal tissue complication probabilities evaluated with the Lyman normal-tissue complication probability model. Physical constraints specify the admissible minimum and maximum target dose. The continuous penalty function method is then used to find an approximate solution of the resulting large-scale constrained minimization problem. Plans generated by our approach are compared to ones produced by a commercial planning system incorporating physical optimization. The comparisons show clinically negligible differences, with the advantage that the hybrid technique does not require specifications of any dose-volume constraints to the normal tissues. This indicates that the proposed hybrid physico-biological method can be used for the generation of clinically acceptable plans.

Algorithms↗
PubMed2003

Dosimetric IMRT verification with a flat-panel EPID.

A convolution-based calibration procedure has been developed to use an amorphous silicon flat-panel electronic portal imaging device (EPID) for accurate dosimetric verification of intensity-modulated radiotherapy (IMRT) treatments. Raw EPID images were deconvolved to accurate, high-resolution 2-D distributions of primary fluence using a scatter kernel composed of two elements: a Monte Carlo generated kernel describing dose deposition in the EPID phosphor, and an empirically derived kernel describing optical photon spreading. Relative fluence profiles measured with the EPID are in very good agreement with those measured with a diamond detector, and exhibit excellent spatial resolution required for IMRT verification. For dosimetric verification, the EPID-measured primary fluences are convolved with a Monte Carlo kernel describing dose deposition in a solid water phantom, and cross-calibrated with ion chamber measurements. Dose distributions measured using the EPID agree to within 2.1% with those measured with film for open fields of 2 x 2 cm2 and 10 x 10 cm2. Predictions of the EPID phantom scattering factors (SPE) based on our scatter kernels are within 1% of the SPE measured for open field sizes of up to 16 x 16 cm2. Pretreatment verifications of step-and-shoot IMRT treatments using the EPID are in good agreement with those performed with film, with a mean percent difference of 0.2 +/- 1.0% for three IMRT treatments (24 fields).

Canada↗
PubMed2002

Derivation of the expressions for gamma50 and D50 for different individual TCP and NTCP models.

This paper presents a complete set of formulae for the position (D50) and the normalized slope (gamma50) of the dose-response relationship based on the most commonly used radiobiological models for tumours as well as for normal tissues. The functional subunit response models (critical element and critical volume) are used in the derivation of the formulae for the normal tissue. Binomial statistics are used to describe the tumour control probability, the functional subunit response as well as the normal tissue complication probability. The formulae are derived for the single hit and linear quadratic models of cell kill in terms of the number of fractions and dose per fraction. It is shown that the functional subunit models predict very steep, almost step-like, normal tissue individual dose-response relationships. Furthermore, the formulae for the normalized gradient depend on the cellular parameters alpha and beta when written in terms of number of fractions, but not when written in terms of dose per fraction.

Computer Simulation↗
PubMed1994

[Fetal development in late gestosis and nicotine consumption].

In pre-eclamptic and in smoking women, the foetus often develops growth retardation. Hence, nicotine as vasoconstrictive substance increases the blood pressure, therefore causes a higher incidence for pre-eclamptic toxaemia in smoking pregnant women. By means of perinatal inquiry in Baden-Württemberg, not only the frequency of preeclamptic toxaemia was proven in smoking women, but also the frequency of toxaemia in mothers with low, of normal and high weight of the newborn. Hypertension is more frequent in mothers with overweight babies than in mothers with babies of normal weight. In case of overweight newborns, toxaemia is less often caused by proteinuria than in underweight babies. Hypertension is less frequent in smoking pregnant women than in non-smoking women. These findings can be explained by a new theory, which interprets pre-eclamptic toxaemia as a compensatory mechanism in foetal growth retardation. For the foetus, which is insufficiently supplied by the placenta, this regulatory mechanism enhances the blood supply of the placenta. The higher incidence of toxaemia in pregnant women with overweight babies is explained by an increased demand on the placenta, which causes a better foetal blood supply of the placenta in developing the toxaemia. In this case, the toxaemia is compensated. In the stage of decompensation with foetal growth retardation, all reserves are mobilised by an increased permeability of the vessels, which leads to an improved passage through the placenta, but also to proteinuria and increased incidence of oedema.(ABSTRACT TRUNCATED AT 250 WORDS)

Birth Weight↗
PubMed1993

[Why are most children born from I. cephalic presentation?].

The question, why most children are delivered in I. cephalic position, is unsolved up to now. Most children are positioned with crossed legs in the uterus. Ultrasonography was employed from the 36th week of gestation onwards to find out whether there is a connection between crossing of the legs and the position in utero. From 58 pregnancies with I. position in 47 cases and from 32 pregnancies with II. position in 28 cases, the leg nearer to the back of the mother was crossed over the other one. According to the neuro-cerebral differentiation between both sides, the foetus prefers a crossing in such a manner, that the left leg is folded over the right leg. The foetus finds a more stable position, if the more mobile leg is directed with the foot against the yielding belly walls of the mother. In accordance with the preferred crossing of the left leg over the right leg the I. position in utero is more frequent.

Female↗
PubMed1991

[Origin of the urge to press in the expulsion period].

So far, the explanation of the bearing-down pains in the expulsion phase has been unsatisfactory. It is assumed that the press reflex is caused by the pressure of the presenting part on the pelvic floor. This is in contradiction to the observation that the press reflex only appears during labour pains and may occur before the presenting part reaches the pelvic floor. In the expulsion phase, the uterine contraction tenses the ligg. cardinaliae, the vagina and the rectal wall in neighbourhood of the vagina. The tension of the rectal wall leads to an urgent need of relieving bowels, which supports the press reflex. By pressing, the woman perceives a pain relief because of a reducement of the tension of the ligg. cardinalia.

Defecation↗
PubMed1990

[Late gestosis as a compensation mechanism in fetal growth retardation and its disruption by antihypertensive therapy].

A study of the clinical course of severe pre-eclamptic toxemias shows that, in case of antihypertensive therapy, it is usually necessary to terminate the pregnancy in cases of foetal maldevelopment, in cases with foetal indication (if no intrauterine death of the foetus takes place), whereas if there is no maldevelopment it is usually a maternal indication that enforces before-term termination of pregnancy. In case of foetal maldevelopment, a drop in HPL and oestriol values was seen. This suggests that the foetal condition deteriorates under antihypertensive treatment. For the foetus, which is deficiently supplied by the placenta, pre-eclamptic toxaemia is a regulatory mechanism of circulation that enhances blood supply of the placenta, since the peripheral resistance in the placental circulation, which is free from vascular nerves, is lower than in the nerve-supplied circulation of the body, on which a hypertensive substance can act. The assumption that such a compensatory mechanism exists is supported by a number of clinical observations. This regulation, which is necessary for the development and perhaps also for the survival of the foetus, is disturbed by the antihypertensive therapy, which explains the deterioration in the condition of the foetus.

Adult↗
PubMed1990

[Relations between psycho-physical acceleration and modern obstetrics].

In the highly developed countries, an acceleration of human growth and an increase in body length can be observed. The weight and length at birth are also increasing, which can be proved by our own investigation. Up to now, the theories explaining this phenomena are insufficient, because they assume the transmission of genetically acquired qualities. The reason for the acceleration is to be considered in the advancement of obstetrics as follows: Obstetrical handling, forceps and caesarean section permit the delivery of large babies, which were often lethal for mother and child. This led to an increase in the frequency of genetic developments for greater body length and weight at birth, which had formerly been limited by the high mortality rate. The trend towards larger babies is caused by an evolutionary selection of an enlargement of the brain, which must reach a certain minimum size by the time of birth. The relative enlargement of the newborn skull, made possible by advanced obstetrics, permits such increased birth weight and length. It also leads to an acceleration of growth and taller adults. The consequence of larger babies is an increasing frequency of obstetrical operations.

Birth Weight↗
PubMed1983

[Diurnal variations in the incidence at premature rupture of the membranes].

Among 8739 deliveries premature rupture of the membranes was noticed in 1.792 cases. The premature rupture of the membranes occurred mostly during the night. During the 8 hours of the night from 2200-0600 hours the membranes ruptured more frequently than during the 16 hours of the day. One would expect that the forewaters break more readily during the daytime because of the upright position, the orthostatic pressure and some shock phenomena. The observed lower incidence of premature rupture of the membranes during the day is explained by protective mechanism which occur like a valve in the upright position.

Circadian Rhythm↗
PubMed1980

[Labour intensity and intervals. A contribution to the problem of origin and spread of uterine contraction (author's transl)].

Basing on external tocograms from the first stage of labour, the intensity of labour was compared with the preceding and subsequent labour interval. The following relative criteria of the intensity of labour were determined: amplitude, medium distance between the upward and downward slope, and the product of the factors. It was found that the intensity of labour depended on the preceding labour interval, whereas no connection between intensity of labour and the subsequent labour interval was noticed. The results are in favour of a myogenous origin and spread of the labour. The longer the muscle fibers are at rest between the individual labours, the more intense will the following labour be, which is produced by spontaneous local contraction.

Female↗
PubMed1979

[Fetal and infantile development of weight, height and constitution and the influence exercised by the placenta and the duration of pregnancy (author's transl)].

Fetal and infantile development of weight and height are studied in relation to period of gestation and weight of placenta. The body weight at birth was selected as a measure of fetal development, whereas the development attained at the age of 6 years served as a measure of intantile growth. Weight and height at birth increase only slightly with increasing duration of pregnancy, whereas there is no cchange in the weight at birth/placental weight ratio. The weight at birth increases with increasing weight of placenta. The quotient weight at birth/weight of placenta increases with a deviation of the weight from the average constitution (represented in this study by the relation between height and weight). Deviations from the mean weight, the mean body height and the mean constitution at birth are still noticeable even when the child has reached the age of six, although on the whole there is evidence of a tendency towards levelling-out. The weight at birth correlates more closely with the placental weight than with the body weight at the age of 6 years. The shorter the period of gestation, the higher the body weight at the age of six. This connection is explained by the action of the feeding centre which participates in both inducing parturition and in developing the body weight. There is no connection between placental weight and body weight at the age of six.

Birth Weight↗