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Reduced optimality in pre- and perinatal conditions in dyskinetic cerebral palsy--distribution and comparison to controls.

The optimality concept developed by Prechtl was adopted to investigate a series of 108 dyskinetic cerebral palsy (CP) cases. The results were compared to those from a control series of 229 newborns. The dyskinetic cases, as compared to the controls, had significantly more reduced optimality scores. Reduced optimality was especially pronounced in the partum and postpartum periods, but was to a highly significant degree also found in the prepartum period. Dystonics and choreoathetotics differed in their pattern of reduced optimality. Dystonics had more reduced optimality in items related to deficient intrauterine growth, intra- and extrauterine asphyxia-choreoathetotics in items related to preterm birth, postpartal hypoxia and hyperbilirubinemia. Term cases had more reduced optimality scores (median 7 vs 1) compared to term controls than preterm cases compared to preterm controls (median 9 vs 4.5). The pattern of reduced optimality in term cases corresponded primarily to that among the dystonics, and the pattern in preterm cases mainly to that of the choreoathetotics. Prepartum warning signals for further partum and postpartum reduced optimality related to the brain cell damage, were maternal disorder, blood group incompatibility and leanness at birth (weight for length less than or equal to -1.0 SD). The latter condition was found to discriminate for reduced optimality in the partum period.

Athetosis

The transepicondylar axis approximates the optimal flexion axis of the knee.

The traditional understanding of knee kinematics holds that no single fixed axis of rotation exists in the knee. In contrast, a recent hypothesis suggests that knee kinematics are better described simply as two simultaneous rotations occurring about fixed axes. Knee flexion and extension occurs about an optimal flexion axis fixed in the femur, whereas tibial internal and external rotations occur about a longitudinal rotation axis fixed in the tibia. No other translations or rotations exist. This hypothesis has been tested. Tibiofemoral kinematics were measured for 15 cadaveric knees undergoing a realistic loadbearing activity (simulated squatting). An optimization technique was used to identify the locations of the optimal flexion and longitudinal rotation axes such that simultaneous rotations about them could best represent the measured kinematics. The optimal flexion axis was compared with the transepicondylar axis defined by bony landmarks. The longitudinal rotation axis was found to pass through the medial joint compartment. The optimal flexion axis passed through the centers of the posterior femoral condyles. No significant difference was found between the optimal flexion and transepicondylar axes. To an average accuracy of better than 3.4 mm in translation, and 2.9 degrees in orientation, knee kinematics were represented successfully by simple rotations about the optimal flexion and longitudinal rotation axes. The optimal flexion axis is fixed in the femur and can be considered the true flexion axis of the knee. The transepicondylar axis axis, which is identified easily by palpation, closely approximates the optimal flexion axis.

Adult

Optimal CT scanning plan for long-bone 3-D reconstruction.

Digital computed tomographic (CT) data are widely used in three-dimensional (3-D) reconstruction of bone geometry and density features for 3-D) modeling purposes. During in vivo CT data acquisition the number of scans must be limited in order to protect patients from the risks related to X-ray absorption. Aim of this work is to automatically define, given a finite number of CT slices, the scanning plan which returns the optimal 3-D) reconstruction of a bone segment from in vivo acquired CT images. An optimization algorithm based on a Discard-Insert-Exchange technique has been developed. In the proposed method the optimal scanning sequence is searched by minimizing the overall reconstruction error of a two-dimensional (2-D) prescanning image: an anterior-posterior (AP) X-ray projection of the bone segment. This approach has been validated in vitro on three different femurs. The 3-D reconstruction errors obtained through the optimization of the scanning plan on the 2-D) prescanning images and on the corresponding 3-D data sets have been compared. Two-dimensional and 3-D data sets have been reconstructed by linear interpolation along the longitudinal axis. Results show that direct 3-D optimization yields root mean square reconstruction errors which are only 4%-7% lower than the 2-D-optimized plan, thus proving that 2-D-optimization provides a good suboptimal scanning plan for 3-D reconstruction. Further on, 3-D reconstruction errors given by the optimized scanning plan and a standard radiological protocol for long bones have been compared. Results show that the optimized plan yields 20%-50% lower 3-D reconstruction errors.

Algorithms

Choosing the optimal monophasic and biphasic waveforms for ventricular defibrillation.

INTRODUCTION: The truncated exponential waveform from an implantable cardioverter defibrillator can be described by three quantities: the leading edge voltage, the waveform duration, and the waveform time constant (tau s). The goal of this work was to develop and test a mathematical model of defibrillation that predicts the optimal durations for monophasic and the first phase of biphasic waveforms for different tau s values. In 1932, Blair used a parallel resistor-capacitor network as a model of the cell membrane to develop an equation that describes stimulation using square waves. We extended Blair's model of stimulation, using a resistor-capacitor network time constant (tau m), equal to 2.8 msec, to explicitly account for the waveform shape of a truncated exponential waveform. This extended model predicted that for monophasic waveforms with tau s of 1.5 msec, leading edge voltage will be constant for waveforms 2 msec and longer; for tau s of 3 msec, leading edge voltage will be constant for waveforms 3 msec and longer; for tau s of 6 msec, leading edge voltage will be constant for waveforms 4 msec and longer. We hypothesized that the best phase 1 of a biphasic waveform is the best monophasic waveform. Therefore, the optimal first phase of a biphasic waveform for a given tau s is the same as the optimal monophasic waveform. METHODS AND RESULTS: We tested these hypotheses in two animal experiments. Part I: Defibrillation thresholds were determined for monophasic waveforms in eight dogs. For tau s of 1.5 msec, waveforms were truncated at 1, 1.5, 2, 2.5, 3, 4, 5, and 6 msec. For tau s of 3 msec, waveforms were truncated at 1,2,3,4,5,6, and 8 msec. For tau s of 6 msec, waveforms were truncated at 2,3,4,5,6,8, and 10 msec. For waveforms with tau s of 1.5, leading edge voltage was not significantly different for the waveform durations of 1.5 msec and longer. For waveforms with tau s of 3 msec, leading edge voltage was not significantly different for waveform durations of 2 msec and longer. For waveforms with tau s of 6 msec, there was no significant difference in leading edge voltage for the waveforms tested. Part II: Defibrillation thresholds were determined in another eight dogs for the same three tau s values. For each value of tau s, six biphasic waveforms were tested: 1/1, 2/2, 3/3, 4/4, 5/5, and 6/6 msec. For waveforms with tau s of 1.5 msec, leading edge voltage was a minimum for the 2/2 msec waveform. For waveforms with tau s of 3 msec, leading edge voltage was a minimum for the 3/3 msec waveform. For waveforms with tau s of 6 msec, leading edge voltage was a minimum and not significantly different for the 3/3, 4/4, 5/5, and 6/6 msec waveforms. CONCLUSIONS: The model predicts the optimal monophasic duration and the first phase of a biphasic waveform to within 1 msec as tau s varies from 1.5 to 6 msec: for tau s equal to 1.5 msec, the optimal monophasic waveform duration and the optimal first phase of a biphasic waveform is 2 msec, for tau s equal to 3.0 msec, the optimal duration is 3 msec, and for tau s equal to 6 msec, the optimal duration is 4 msec. For both monophasic and biphasic waveforms, optimal waveform duration shortens as the waveform time constant shortens.

Animals

Prediction of antagonistic muscle forces using inverse dynamic optimization during flexion/extension of the knee.

This paper examined the feasibility of using different optimization criteria in inverse dynamic optimization to predict antagonistic muscle forces and joint reaction forces during isokinetic flexion/extension and isometric extension exercises of the knee. Both quadriceps and hamstrings muscle groups were included in this study. The knee joint motion included flexion/extension, varus/valgus, and internal/external rotations. Four linear, nonlinear, and physiological optimization criteria were utilized in the optimization procedure. All optimization criteria adopted in this paper were shown to be able to predict antagonistic muscle contraction during flexion and extension of the knee. The predicted muscle forces were compared in temporal patterns with EMG activities (averaged data measured from five subjects). Joint reaction forces were predicted to be similar using all optimization criteria. In comparison with previous studies, these results suggested that the kinematic information involved in the inverse dynamic optimization plays an important role in prediction of the recruitment of antagonistic muscles rather than the selection of a particular optimization criterion. Therefore, it might be concluded that a properly formulated inverse dynamic optimization procedure should describe the knee joint rotation in three orthogonal planes.

Algorithms

Evaluation of the OptiMAL test for rapid diagnosis of Plasmodium vivax and Plasmodium falciparum malaria.

The development of rapid and specific diagnostic tests to identify individuals infected with malaria is of paramount importance in efforts to control the severe public health impact of this disease. This study evaluated the ability of a newly developed rapid malaria diagnostic test, OptiMAL (Flow Inc., Portland, Oreg.), to detect Plasmodium vivax and Plasmodium falciparum malaria during an outbreak in Honduras. OptiMAL is a rapid (10-min) malaria detection test which utilizes a dipstick coated with monoclonal antibodies against the intracellular metabolic enzyme parasite lactate dehydrogenase (pLDH). Differentiation of malaria parasites is based on antigenic differences between the pLDH isoforms. Since pLDH is produced only by live Plasmodium parasites, this test has the ability to differentiate live from dead organisms. Results from the OptiMAL test were compared to those obtained by reading 100 fields of traditional Giemsa-stained thick-smear blood films. Whole-blood samples were obtained from 202 patients suspected of having malaria. A total of 96 samples (48%) were positive by blood films, while 91 (45%) were positive by the OptiMAL test. The blood films indicated that 82% (79 of 96) of the patients were positive for P. vivax and 18% (17 of 96) were infected with P. falciparum. The OptiMAL test showed that 81% (74 of 91) were positive for P. vivax and 19% (17 of 91) were positive for P. falciparum. These results demonstrated that the OptiMAL test had sensitivities of 94 and 88% and specificities of 100 and 99%, respectively, when compared to traditional blood films for the detection of P. vivax and P. falciparum malaria. Blood samples not identified by OptiMAL as malaria positive normally contained parasites at concentrations of less than 100/microl of blood. Samples found to contain P. falciparum were further tested by two other commercially available rapid malaria diagnostic tests, ParaSight-F (Becton Dickinson, Cockeysville, Md.) and ICT Malaria P.f. (ICT Diagnostics, Sydney, Australia), both of which detect only P. falciparum. Only 11 of the 17 (65%) P. falciparum-positive blood samples were identified by the ICT and ParaSight-F tests. Thus, OptiMAL correctly identified P. falciparum malaria parasites in patient blood samples more often than did the other two commercially available diagnostic tests and showed an excellent correlation with traditional blood films in the identification of both P. vivax malaria and P. falciparum malaria. We conclude that the OptiMAL test is an effective tool for the rapid diagnosis of malaria.

Humans

Constrained optimization of ventricular efficiency in normal and failing hearts.

Optimal ventriculoarterial coupling, in terms of maximal energetic efficiency, was recently analyzed by analytic and experimental studies. Whereas for normal hearts the analytic predictions agreed well with measured data, failing hearts were found to operate remote from the predicted optimal conditions. An analysis of optimal coupling is developed in the present study, based on constrained optimization. The constraints are based on the concept that the system must comply with physiological requirements (restrictions) under all conditions. Optimization using the mean pressure as a constraint yielded results similar to the unconstrained case in the normal heart but different with the failing heart: in the failing heart the optimal arterial elastance was found to be larger than the ventricular elastance, whereas the opposite was predicted by the unconstrained optimization. If an additional constraint on the end-systolic pressure is used, a unique solution of the coupling state is obtained. The predicted coupling ratio was found to match published data from normal subjects and heart failure patients, where in the latter group it was found to be remote from the optimal efficiency state. An increase in ventricular contractility and reduction in afterload were shown to shift the nonoptimal coupling state toward the optimal one. This prediction complies with the use of inotropic agents and vasodilators as the mainstay of heart failure treatment. This study may provide a convenient framework of analysis for the assessment of the ventriculoarterial coupling and for the evaluation of the cardiovascular effects of specific drug treatments.

Blood Pressure

Optimization of temperature distributions in scanned, focused ultrasound hyperthermia.

Scanned, focused ultrasound systems (SFUS) have considerable flexibility in shaping the power deposition field during hyperthermia treatments. When utilizing this adaptability many complicated, interacting decisions must be made to obtain an optimal steady-state temperature distribution. This optimization problem is studied using a 3-D, radially symmetric simulation program which searches for a set of optimal scan parameters. The conjugate-gradient optimization technique with a golden section search was used to obtain the optimal temperature distributions attainable with a single circular scan of a tumour. The variable scan parameters of the single transducer heating system optimized (and under the control of the therapist) are: transducer tilt and rotation angles, focal depth, output acoustical power, and scan radius. This single scan study includes the effects of tumour and normal tissue blood perfusions, tumour depth, skin temperature boundary condition, as well as tumour size and shape. A similar, but less comprehensive, study was done for larger tumours using two concentric circular scans. The results show that (1) the optimization process can produce a set of scan parameters that give a considerably better temperature distribution than could be obtained ad hoc, and (2) the optimal scan parameter configuration obtained produces a close-to-ideal tumour temperature distribution for a wide variety of clinically relevant conditions. Thus, when extended to include data from individual patients such optimization should be a very useful tool in patient treatment planning, and should enhance the present capabilities of clinical scanned, focused ultrasound systems.

Body Temperature

Optimal sample allocation in clinical trials designed to investigate relative risks.

Clinical trials with more than two groups are becoming increasingly common, especially trials with both active and placebo control groups. Equal allocation of subjects to each of the groups is the most common sample allocation, but in clinical trials where the purpose is to test hypotheses of relative risk, such as vaccine trials, equal allocation can be substantially sub-optimal. Optimal allocation for clinical trials has been considered previously, but not for trials with more than two groups. In this paper optimal sample allocation for relative risk trials is investigated in a variety of situations. The main results are as follows: (i) there are many situations where reductions of more than 20 per cent in sample size can be obtained by using optimal allocation instead of equal allocation; (ii) the optimal allocation for two group studies is not optimal in general; (iii) in many situations optimal allocation increases a subject's chances of being enrolled to a test treatment, and (iv) in most cases a grid search using the likelihood score asymptotic power function is the easiest method of finding an approximately optimal allocation. Extensions to situations more general than those covered here are sketched.

Case-Control Studies

Optimization of the electrostatic interactions in proteins of different functional and folding type.

The 3-dimensional optimization of the electrostatic interactions between the charged amino acid residues was studied by Monte Carlo simulations on an extended representative set of 141 protein structures with known atomic coordinates. The proteins were classified by different functional and structural criteria, and the optimization of the electrostatic interactions was analyzed. The optimization parameters were obtained by comparison of the contribution of charge-charge interactions to the free energy of the native protein structures and for a large number of randomly distributed charge constellations obtained by the Monte Carlo technique. On the basis of the results obtained, one can conclude that the charge-charge interactions are better optimized in the enzymes than in the proteins without enzymatic functions. Proteins that belong to the mixed alpha beta folding type are electrostatically better optimized than pure alpha-helical or beta-strand structures. Proteins that are stabilized by disulfide bonds show a lower degree of electrostatic optimization. The electrostatic interactions in a native protein are effectively optimized by rejection of the conformers that lead to repulsive charge-charge interactions. Particularly, the rejection of the repulsive contacts seems to be a major goal in the protein folding process. The dependence of the optimization parameters on the choice of the potential function was tested. The majority of the potential functions gave practically identical results.

Computer Simulation

A model of optimal voluntary muscular control.

In the absence of detailed knowledge of how the CNS controls a muscle through its motor fibers, a reasonable hypothesis is that of optimal control. This hypothesis is studied using a simplified mathematical model of a single muscle, based on A.V. Hill's equations, with series elastic element omitted, and with the motor signal represented by a single input variable. Two cost functions were used. The first was total energy expended by the muscle (work plus heat). If the load is a constant force, with no inertia, Hill's optimal velocity of shortening results. If the load includes a mass, analysis by optimal control theory shows that the motor signal to the muscle consists of three phases: (1) maximal stimulation to accelerate the mass to the optimal velocity as quickly as possible, (2) an intermediate level of stimulation to hold the velocity at its optimal value, once reached, and (3) zero stimulation, to permit the mass to slow down, as quickly as possible, to zero velocity at the specified distance shortened. If the latter distance is too small, or the mass too large, the optimal velocity is not reached, and phase (2) is absent. For lengthening, there is no optimal velocity; there are only two phases, zero stimulation followed by maximal stimulation. The second cost function was total time. The optimal control for shortening consists of only phases (1) and (3) above, and is identical to the minimal energy control whenever phase (2) is absent from the latter. Generalization of this model to include viscous loads and a series elastic element are discussed.

Biophysical Phenomena

DESIGN: computerized optimization of experimental design for estimating Kd and Bmax in ligand binding experiments. I. Homologous and heterologous binding to one or two classes of sites.

We have developed a versatile computer program for optimization of ligand binding experiments (e.g., radioreceptor assay system for hormones, drugs, etc.). This optimization algorithm is based on an overall measure of precision of the parameter estimates (D-optimality). The program DESIGN uses an exact mathematical model of the equilibrium ligand binding system with up to two ligands binding to any number of classes of binding sites. The program produces a minimal list of the optimal ligand concentrations for use in the binding experiment. This potentially reduces the time and cost necessary to perform a binding experiment. The program allows comparison of any proposed experimental design with the D-optimal design or with assay protocols in current use. The level of nonspecific binding is regarded as an unknown parameter of the system, along with the affinity constant (Kd) and binding capacity (Bmax). Selected parameters can be fixed at constant values and thereby excluded from the optimization algorithm. Emphasis may be placed on improving the precision of a single parameter or on improving the precision of all the parameters simultaneously. We present optimal designs for several of the more commonly used assay protocols (saturation binding with a single labeled ligand, competition or displacement curve, one or two classes of binding sites), and evaluate the robustness of these designs to changes in parameter values of the underlying models. We also derive the theoretical D-optimal design for the saturation binding experiment with a homogeneous receptor class.

Binding Sites

Implementation of OSPOP, an algorithm for the estimation of optimal sampling times in pharmacokinetics by the ED, EID and API criteria.

The most common approach to optimize the sampling schedule in parameter estimation experiments is the D-optimality criterion, which consists in maximizing the determinant of the Fisher information matrix (max det F). In order to incorporate prior parameter uncertainty in the optimal design, other criteria have been proposed: The ED = max E (det F), EID = min E (l/det F) and API = max E (log det F) criteria, where the expectation is with respect to the given prior distribution of the parameters. Previously described algorithm for the estimation of optimal sampling times according to these criteria are adaptive random search (ARS), a robust and global but slow optimizer for API, and stochastic gradient (SG), a fast but local optimizer for ED and EID. We implemented an algorithm named OSPOP 1.0, based on non-adaptive random search (RS) followed by stochastic gradient to determine optimal sampling times for parameter estimation in various pharmacokinetic models according to ED, EID and API criteria. Prior distributions are allowed to be uniform, normal or lognormal. This algorithm combines the robustness of RS and the speediness of SG (convergence is obtained in a few minutes on a microcomputer). The results of the SG algorithm have been compared to those described in the literature using the ARS algorithm on a one compartment model with first- order absorption and were very similar. Also, the CPU time needed by SG and ARS algorithms were compared and the former proved to be much faster. Then, it has been applied to a five parameters stochastic model with zero-order absorption rate and Weibull-distributed residence times which was shown to describe adequately the kinetics of metacycline in humans. Population pharmacokinetic parameters of metacycline were estimated from a six subject pilot study, by the iterative two-staged method, using ADAPT II repeatedly. Optimal sampling times were determined with each criterion (ED, EID, API) with a multivariate normal prior parameter distribution. Six to seven distinct sampling times could be estimated. Higher numbers of samples revealed coalescing of design points.

Algorithms

The optimality concept and its clinical value.

To verify the clinical usefulness of the optimality concept in general and its prognostic value for later outcome, all babies born at all 14 maternity hospitals in Slovenia in the period from 1987 to 1991 (124,759 newborns) have been screened. In order to get an estimate of their condition Prechtl's original list of optimality has been adapted to 51 items representing mostly obstetric variables. The median of perinatal optimality scores for all newborns was 45 (six negative points) in mature, and 41 (10 negative points) in premature infants. Girls born at term scored better than mature boys, whereas there was no sex difference in the median score in prematures. Analysis of the data has shown that the majority of items which were non-optimal and which were associated with the greatest number of other non-optimal factors had to do with disturbances in oxygen supply. Children who developed cerebral palsy had a lower optimality score at birth than the remainder of the newborns. In these children the difference between the sexes is even more pronounced, to the advantage of the girls. Prematurely born children with spastic diplegia had a lower optimality score than mature children with diplegia. The opposite was noticed in children born prematurely and at term who developed spastic tetraparesis or dyskinesia. The present follow-up study has shown that predictions of disability were most accurate in the group of newborns who were clinically at risk at birth and who also had a low optimality score. The combination of both appraisals is the best way to identify newborns who need special attention.

Apgar Score

3D conformal intensity-modulated radiotherapy planning: interactive optimization by constrained matrix inversion.

BACKGROUND AND PURPOSE: This paper presents a method for interactive optimization of 3D conformal intensity-modulated radiotherapy plans employing a quadratic objective that also contains dose limitations in the organs at risk. This objective function is minimized by constrained matrix inversion (CMI) that follows the same approach as the gradient technique using matrix notation. MATERIALS AND METHODS: Sherouse's GRATIS radiotherapy design system is used to determine the outlines of the target volume and the organs at risk and to input beam segments which are given by the beam segmentation technique. This technique defines the beam incidences and the beam segmentation. The weights of the segments are then calculated using a quadratic objective function and CMI. The objective function to be minimized consists of two components based on the planning target volume (PTV) and the organ at risk (OAR) with an importance factor w associated with the OAR. RESULTS: Optimization is tested for concave targets in the head and neck region wrapping around the spinal cord. For a predefined w-value, segment weights are optimized within a few seconds on a DEC Alpha 3000. In practice, 5-10 w-values have to be tested, making optimization a less than 5 min procedure. This optimization procedure predicts the possibility of target dose escalation for a tumour in the lower neck to 120-150 Gy without exceeding the spinal cord tolerance, whereas human planners could not increase the dose above 65-80 Gy. CONCLUSIONS: Treatment plans optimized using a quadratic objective function and the CMI algorithm are superior to those which are generated by human planners. The optimization algorithm is very fast and allows interactive use. Quadratic optimization by CMI is routinely used by clinicians at the Division of Radiotherapy, U.Z.-Gent.

Equipment Design

Comparison of ED, EID, and API criteria for the robust optimization of sampling times in pharmacokinetics.

Optimization of the sampling schedule can be used in pharmacokinetic (PK) experiments to increase the accuracy and the precision of parameter estimation or to reduce the number of samples required. Several optimization criteria that formally incorporate prior parameter uncertainty have been proposed earlier. These criteria consist in finding the sampling schedule that maximizes the expectation (over a given parameter distribution) of det F (ED-optimality) or Log(det F) (API-optimality), or minimizes the expectation of 1/det F (EID-optimality), where F is the Fisher information matrix. The precision and the accuracy of parameter estimation after having fitted a PK model to a small number of optimal data points (determined according to D, ED, EID, and API criteria) or to a naive sampling schedule were compared in a Monte Carlo simulation study. A one-compartment model with first-order absorption rate (3 parameters) and a two-compartment model with zero-order infusion rate (4 parameters) were considered. Data were simulated for 300 subjects with both structural models, combined with several residual error models (homoscedastic, heteroscedastic with constant or variable coefficient of variation). Interindividual variabilities in PK parameters ranged from 25-66%. ED-, EID-, and API-optimal sampling times were calculated using the software OSP-Fit. Three or five samples were allowed for parameter estimation by extended least-squares. Performances of each design criterion were evaluated in terms of mean prediction error, root mean squared error, and number of acceptable estimates (i.e., with a SE less than 30%). Compared to the D-optimal design, the EID and API designs reduced the bias and the imprecision of the estimation of the parameters having a large interindividual variability. Moreover, the API design resulted in some cases in a higher number of acceptable estimates.

Models, Biological

Electrical defibrillation optimization: an automated, iterative parallel finite-element approach.

To date, optimization of electrode systems for electrical defibrillation has been limited to hand-selected electrode configurations. In this paper we present an automated approach which combines detailed, three-dimensional (3-D) finite-element torso models with optimization techniques to provide a flexible analysis and design tool for electrical defibrillation optimization. Specifically, a parallel direct search (PDS) optimization technique is used with a representative objective function to find an electrode configuration which corresponds to the satisfaction of a postulated defibrillation criterion with a minimum amount of power and a low possibility of myocardium damage. For adequate representation of the thoracic inhomogeneities, 3-D finite-element torso models are used in the objective function computations. The CPU-intensive finite-element calculations required for the objective function evaluation have been implemented on a message-passing parallel computer in order to complete the optimization calculations in a timely manner. To illustrate the optimization procedure, it has been applied to a representative electrode configuration for transmyocardial defibrillation, namely the subcutaneous patch-right ventricular catheter (SP-RVC) system. Sensitivity of the optimal solutions to various tissue conductivities has been studied. Results for the optimization of defibrillation systems are presented which demonstrate the feasibility of the approach.

Algorithms

Optimized dynamic rotation with wedges.

Dynamic rotation is a computer-controlled therapy technique utilizing an automated multileaf collimator in which the radiation beam shape changes dynamically as the treatment machine rotates about the patient so that at each instant the beam shape matches the projected shape of the target volume. In simple dynamic rotation, the dose rate remains constant during rotation. For optimized dynamic rotation, the dose rate is varied as a function of gantry angle. Optimum dose rate at each gantry angle is computed by linear programming. Wedges can be included in the optimized dynamic rotation therapy by using additional rotations. Simple and optimized dynamic rotation treatment plans, with and without wedges, for a pancreatic tumor have been compared using optimization cost function values, normal tissue complication probabilities, and positive difference statistic values. For planning purposes, a continuous rotation is approximated by static beams at a number of gantry angles equally spaced about the patient. In theory, the quality of optimized treatment planning solutions should improve as the number of static beams increases. The addition of wedges should further improve dose distributions. For the case studied, no significant improvements were seen for more than 36 beam angles. Open and wedged optimized dynamic rotations were better than simple dynamic rotation, but wedged optimized dynamic rotation showed no definitive improvement over open beam optimized dynamic rotation.

Humans