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Biomedical subjects

A Niemierko

Publications and source records attributed to A Niemierko.

16 recordsLinked to original sources

Random search algorithm (RONSC) for optimization of radiation therapy with both physical and biological end points and constraints.

A new algorithm for the optimization of 3-dimensional radiotherapy plans is presented. The RONSC algorithm (Random Optimization with Non-linear Score functions and Constraints) is based on the idea of random search in the space of feasible solutions. RONSC takes advantage of some specific properties of the dose distribution and derivable information such as dose-volume histograms and calculated estimates of tumor control and normal tissue complication probabilities. The performance of the algorithm for clinical and test cases is discussed and compared with the performance of the simulated annealing algorithm, which is also based on the idea of random search.

Algorithms

Optimization of 3D radiation therapy with both physical and biological end points and constraints.

A new optimization model is described and its clinical usefulness is demonstrated. The optimization technique was developed to allow computer optimization of 3-dimensional radiation therapy plans with biological models of tumor and normal tissue response to radiation as well as with scores based on physical dose. The emphasis was placed on the optimization model, which should describe, as closely as possible, the goal of the radiation treatment, which is eradication of the tumor while sparing normal tissues. Since the statement of the goals may vary from case to case, a technique that allows a variety of objective functions and types of constraints was developed. The optimization algorithm is capable of handling nonlinear and even discrete score (objective) functions and constraints and effectively explores the vast space of feasible solutions in a relatively short time (minutes of MicroVax 3200 CPU time). An example of computer optimization of radiation therapy of a chordoma of the sphenoid bone using x-ray and proton beams is shown and compared with the best plans achieved by an experienced planner. Directions for future development of the algorithm, allowing optimization of beam orientation, are presented.

Chordoma

Effect of phorbol ester PMA and puromycin on the maturation of mouse oocytes.

The effect of phorbol myristate acetate (PMA) and puromycin (PU) on maturation divisions of mouse oocytes was investigated. PMA changed the morphology and function of the spindle in meiosis I. The spindle had a broad polar region and did not commence karyokinesis in the first maturation division. This persisted in 25% of spindles which were passive up to 30 h of maturation. Half of the oocytes with spindles blocked by PMA between 20 and 30 h of maturation became activated, and 25% of the initial pool underwent abortive karyokinesis consisting of segregation of several chromosomes of the metaphase plate. Cytological observation indicated that the presence of PMA interfered with the elongation of the spindle in anaphase. Under the condition of changed phosphorylation of maturation of proteins by PMA, a reversible interphase was induced by PU. Most of the nuclei induced by PU exhibited pronuclei. A new class of nuclei induced by PU with condensed chromatin and having no nucleoli is described. The mechanism and consequences of interference of PMA on anaphase are discussed.

Animals

Calculation of normal tissue complication probability and dose-volume histogram reduction schemes for tissues with a critical element architecture.

We investigate a model of normal tissue complication probability for tissues that may be represented by a critical element architecture. We derive formulas for complication probability that apply to both a partial volume irradiation and to an arbitrary inhomogeneous dose distribution. The dose-volume isoeffect relationship which is a consequence of a critical element architecture is discussed and compared to the empirical power law relationship. A dose-volume histogram reduction scheme for a "pure" critical element model is derived. In addition, a point-based algorithm which does not require precomputation of a dose-volume histogram is derived. The existing published dose-volume histogram reduction algorithms are analyzed. We show that the existing algorithms, developed empirically without an explicit biophysical model, have a close relationship to the critical element model at low levels of complication probability. However, we also show that they have aspects which are not compatible with a critical element model and we propose a modification to one of them to circumvent its restriction to low complication probabilities.

Algorithms

Properties of the zona pellucida of cytochalasin B-induced triploid mouse eggs.

The hardening of the zona pellucida as a result of the cortical reaction was estimated in triploid oocytes produced with cytochalasin B by two different procedures. Triploid oocytes resulting from fertilization in the presence of cytochalasin B did not reveal hardening of the zona pellucida unlike triploids obtained by inhibiting in-vitro extrusion of the second polar body in oocytes fertilized in vivo.

Animals

Action of phorbol myristate acetate (PMA) at fertilization of mouse oocytes in vitro.

Phorbol ester (PMA) in concentration 5 and 10 ng ml-1 blocks cytokinesis of the second maturation division in mouse oocytes. Karyokinesis is not impaired and digynic triploid oocytes are obtained which undergo first cleavage division. Effectiveness of blocking cytokinesis is dependent on the timing of exposure of oocytes to PMA action. When oocytes are subjected to PMA at the onset of the second maturation division only 14.5% of eggs are triploid. PMA present during fertilization in vitro (about 1 h exposure to PMA) induces triploidy in 40% eggs. Extending the time of exposure of oocytes to 2 h produces 76% tripronucleate eggs. Applicability of PMA is compared with the use of cytochalasin B to induce triploidy in the mouse.

Animals

Postimplantation development of CB-induced triploid mouse embryos.

By subjecting A strain eggs at the time of fertilization and polar body extrusion to 5 micrograms/ml cytochalasin B, digynic triploidy was produced in 80% fertilized eggs. Triplonucleate eggs were transplanted to recipients and examined between 9-11th day of pregnancy. Development of triploid mouse embryos up to day 7 is normal and most embryos form early egg cylinder. At day 8 the embryonic part of the cylinders is under-developed and later development fails to form an embryo. Development of foetal membranes is much less affected, CB-induced triploids survive to 10th- day of pregnancy.

Animals

[Induction of triploidy and the development of triploid mouse embryos].

By subjecting A strain eggs at the time of fertilization and polar body extrusion to 5 micrograms ml cytochalasin B digynic triploidy was produced in 80% fertilized eggs. 50% tripronuceate eggs developed into regular morulae and blastocysts with 2/3 the cell number of control diploids. Tripronuceate eggs were transplanted to recipients and examined between 9-11 th day of pregnancy. Development of triploid embryos up to 7 day is normal and most embryos form egg-cylinder. At 8 day embryonic part of the cylinders is underdeveloped and in latter development fails to form an embryo. Development of foetal membranes is much less affected and in successfully developing egg-cylinders their formation can be fully accomplished. Failure of embryonic development appears to be due to lower proliferation rate triploid cells than diploid, subnormal activity primitive streak, resulting, in shortage of mesoderm.

Animals

Factors regulating the degree and extent of experimental chimaerism in the mouse.

The degree of chimaerism of the coat, bone marrow and cornea in mouse chimaeras obtained by aggregation of an albino inbred embryo of A strain with an A X CBA-T6T6 hybrid was investigated. Out of 21 individuals born, 18 were chimaeras. Statistically significant correlation has been demonstrated between chimaerism of the coat, bone marrow and the cornea. The contribution of the two components appears to be affected by two factors: first, variable participation of the two components inthe embryonic ectoderm of the chimaeric egg cyclinder, and second, the rate of proliferation of the two cell lines. A photometric method is described which permits the quantitative evaluation of coat chimaerism. The method is sensitive and reliable.

Animals

Cytochalasin B-induced triploidy in mouse oocytes fertilized in vitro.

Mouse eggs and spermatozoa were treated in various ways with 5 or 10 mug cytochalasin B/ml. The fertilization rate in vitro was reduced by treatment with the drug but 80-90% of the eggs fertilized were triploid. Many of the experimental eggs were penetrated by one or more spermatozoa but remained unfertilized (75% compared with 9% in control eggs). It is suggested that cytochalasin B weakens the zona reaction and interferes with fusion of gametes but does not prevent the block to polyspermy.

Animals

Induction of triploidy in the mouse by cytochalasin B.

Mouse eggs fertilized in vivo were treated with cytochalasin B in vitro (5 mug/ml of culture medium) at the moment of extrusion of the second polar body (2-5, 3-0, 3-5 h after copulation). Cytochalasin B inhibits cytokinesis of the second maturation division, so that triploid digynic eggs are formed in over 50% of treated eggs. Triploid eggs were transplanted to the oviducts of recipients. On the 4th and 5th day of development 41-7% of transplanted eggs were recovered. All embryos recovered on the 4th day were morulae, while on the 5th day blastocysts predominated. Recovered embryos were studied for cell number and ploidy. Twenty-three of 27 embryos with analysable metaphase plates were triploid and four were diploid (the latter were found in females into which both triploid and control diploid eggs were transplanted). Sex chromosome constitution was determined in seven cases: four triploids were XXY and three were XXX. Preliminary observations showed that triploid embryos obtained by the use of cytochalasin B can implant and survive at least to the 9th day.

Animals

The influence of the size of the grid used for dose calculation on the accuracy of dose estimation.

The standard presentation of a dose distribution as an isodose map is based on interpolation between dose values calculated on a matrix of equally spaced points. We explored the question of how the spacing of the grid used for the dose matrix affects the error due to interpolating the dose at any point. We defined two types of errors: the dose error, which is the difference between the interpolated and true dose at a given point; and the position error, which is the distance between the point of interest and the nearest point which has, in fact, the dose value estimated for the point of interest. We examine the problem using both an analytical beam profile (a Fermi function) and measured 60Co, x-ray and proton beam profiles. Our analysis showed that the interpolation errors are proportional to the curvature of the dose distribution and are relatively high in regions on either side of, but not including, the steepest part of the penumbra. Our results showed how big an interpolation error one should expect for a given size of the calculation grid. The specification of accuracy should be cast in the form of a pair of requirements, one for dose and the other for position. At a given point, only one of the two requirements needs to be satisfied. The position requirement is almost always the less demanding in clinical practice and permits the use of a larger grid spacing than if only a dose requirement is applied.(ABSTRACT TRUNCATED AT 250 WORDS)

Cobalt Radioisotopes

The use of variable grid spacing to accelerate dose calculations.

Planning radiation therapy using three-dimensional patient data is a very time consuming process with current hardware and software. When calculating a three-dimensional dose distribution, the standard technique is to cover the volume of interest with a uniformly spaced matrix of points at which the dose is calculated. It is obvious that the dose is usually quite slowly varying in a large proportion of the region of interest; namely, in those regions which are either well inside or well outside the geometrical boundaries of the field. We have developed an algorithm which allows us to reduce the number of calculation points, and hence the time of calculation of the entire dose distribution, manyfold. We use a nonuniform grid of calculated points, based on the fact that the only regions which are troublesome for accurate dose interpolation are those in which large values of the second derivative of the dose as a function of position occur. We demonstrate that, at most grid points, the dose can be determined without decreasing accuracy below acceptable limits by simple linear interpolation between grid points much further apart than is usual in conventional techniques. We investigated our algorithm for one-, two-, and three-dimensional examples and for Co-60, 25-MV photon, and 160-MV proton beams. In situations for which an accuracy of about 1% in dose and 1.6 mm in position was desired, we found gain factors for the number of points needing direct calculation of approximately 3 (one-dimension), 6 to 10 (two-dimensions) and 16 (three-dimensions).

Algorithms

Random sampling for evaluating treatment plans.

We analyze the influence of sampling technique on the accuracy of estimating irradiated volumes, dose-volume histograms and tumor control and normal tissue complication probabilities. The sampling techniques we consider are uniform distribution of points on a regular Cartesian grid and random selection of points. For three-dimensional treatment planning, random sampling leads to a significant reduction in estimation error and/or in the number of calculation points necessary to achieve a required accuracy. We discuss advantages and drawbacks of random sampling, as compared to sampling on a regular grid. It is suggested that, in practical situations, at least 50 times fewer randomly sampled points per organ/volume of interest are needed for fast estimation of complication probability with the same accuracy, i.e., not exceeding 5% (within 95% confidence limits) in the worst case.

Evaluation Studies as Topic