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Results for “Optimization”

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PubMed1997

A prospective randomized trial of preoperative "optimization" of cardiac function in patients undergoing elective peripheral vascular surgery.

BACKGROUND: Previous investigations have suggested that preoperative invasive hemodynamic monitoring with "optimization" of cardiovascular function may favorably affect the outcome among patients undergoing peripheral vascular surgery. The purpose of this study was to evaluate the effect of preoperative optimization of hemodynamic parameters on outcome in patients undergoing aortic reconstruction (AR) or limb salvage procedures (LSP) in a randomized, prospective clinical trial. METHODS: All 72 patients who consented to participate in this study were admitted to the intensive care unit at least 12 hours before operation for placement of a pulmonary artery catheter (PAC). Patients who were randomized to the treatment group (n = 32) were "optimized" by adjusting their hemoglobin concentration, oxygen saturation (SaO2), cardiac output, or afterload until the mixed venous O2 saturation (SvO2) was at least 65%. The control group (n = 40) underwent placement of a PAC and had oxygen transport parameters measured without any attempt to optimize SvO2. RESULTS: There were no significant differences between the treatment and control groups with respect to age, gender, type of operation, initial Acute Physiology and Chronic Health Evaluation (APACHE) II score, SvO2, pulmonary artery occlusion pressure, or cardiac index. All treatment patients achieved an SvO2 of at least 65% before operation. Comparing the treatment and control groups, postoperative cardiovascular complications occurred in 25% versus 27%, intraoperative complications in 28% versus 20%, and death in 9% versus 5%, respectively. None of these differences was statistically significant as a whole or within the subgroups undergoing AR or LSP. CONCLUSIONS: These data suggest that preoperative optimization of cardiovascular function by using achievement of SvO2 above 65% as the end point does not result in any reduction of intraoperative or perioperative cardiac complications in patients undergoing PVS. Further studies with alternative assessments and manipulation of different cardiopulmonary parameters may yield additional information.

Aged↗

PubMed2003

Do humans optimally integrate stereo and texture information for judgments of surface slant?

An optimal linear system for integrating visual cues to 3D surface geometry weights cues in inverse proportion to their uncertainty. The problem of integrating texture and stereo information for judgments of planar surface slant provides a strong test of optimality in human perception. Since the accuracy of slant from texture judgments changes by an order of magnitude from low to high slants, optimality predicts corresponding changes in cue weights as a function of surface slant. Furthermore, since humans show significant individual differences in their abilities to use both texture and stereo information for judgments of 3D surface geometry, the problem admits the stronger test that individual differences in subjects' thresholds for discriminating slant from the individual cues should predict individual differences in cue weights. We tested both predictions by measuring slant discrimination thresholds and stereo/texture cue weights as a function of surface slant for multiple subjects. The results bear out both predictions of optimality, with the exception of an apparent slight under-weighting of texture information. This may be accounted for by factors specific to the stimuli used to isolate stereo information in the experiments. Taken together, the results are consistent with the hypothesis that humans optimally combine the two cues to surface slant, with cue weights proportional to the subjective reliability of the cues.

Cues↗

PubMed1999

Optimal integration of texture and motion cues to depth.

We report the results of a depth-matching experiment in which subjects were asked to adjust the height of an ellipse until it matched the depth of a simulated cylinder defined by texture and motion cues. In one-third of the trials the shape of the cylinder was primarily given by motion information, in another one-third of the trials it was given by texture information, and on the remaining trials it was given by both sources of information. Two optimal cue combination models are described where optimality is defined in terms of Bayesian statistics. The parameter values of the models are set based on subjects' responses on trials when either the motion cue or the texture cue was informative. These models provide predictions of subjects' responses on trials when both cues were informative. The results indicate that one of the optimal models provides a good fit to the subjects' data, and the second model provides an exceptional fit. Because the predictions of the optimal models closely match the experimental data, we conclude that observers' cue-combination strategies are indeed optimal, at least under the conditions studied here.

Contrast Sensitivity↗

PubMed2000

The optimal transarticular c1-2 screw length and the location of the hypoglossal nerve.

BACKGROUND: Injury to the hypoglossal nerve is a complication associated with transarticular C1-2 screw placement. This complication can be caused by a misdirected or too long screw. Little is known about the optimal screw length and its relationship to the hypoglossal nerve. METHODS: Twenty cervical spine specimens were used to study the optimal length of the transarticular C1-2 screw. Using the Magerl technique, a 3.0 mm drill bit was inserted into the C2 lateral mass, passing through the C1-2 facet joint and penetrating the upper portion of the ventral cortex of the lateral mass of the atlas. After drilling, the hole length was measured between the dorsal cortex of the C2 inferior articular process and the ventral cortex of the C1 lateral mass. In addition, six sagittal-sectioned cadavers were carefully dissected to observe the location of the hypoglossal nerve in the anterior aspect of the atlantoaxial region. RESULTS: The results of the measurements showed that the mean optimal screw path length for all specimens was 38.1 +/- 2.2 mm with a range of 34-43 mm. There was no significant difference between sexes in the screw path length (p 0.05). The hypoglossal nerve lies vertically in front of the lateral portion of the C1 lateral mass and the C1-2 facet joint. The area where the hypoglossal nerve lies is approximately 2-3 mm lateral to the middle of the anterior aspect of the C1 lateral mass. CONCLUSIONS: This study suggests that the mean optimal transarticular C1-2 screw length may be 38 mm; however, the determination of the accurate optimal C1-2 screw length should be made on an individual basis. Risk to the hypoglossal nerve can be eliminated if Magerl's technique is performed exactly.

Aged↗

PubMed2001

Optimal duration of therapy with trastuzumab.

One of the primary objectives of early clinical drug development is to determine the optimal dose and schedule of administration of the drug under study. If this objective is accomplished, subsequent clinical trials can truly evaluate the antitumor efficacy, tolerability, and safety of the new drug, and the appropriate assessment of benefit/risk can be made. A full understanding of the mechanisms not only of antitumor activity but also of side effects and toxicity is critical to select the optimal schedule of administration. In this regard, preclinical (in vitro and in vivo) studies are often helpful before clinical studies are initiated. However, no preclinical model is fully predictive of the outcome of human clinical trials. Therefore, while preclinical studies can point to potentially fruitful directions in clinical investigation, only after fairly substantial clinical experience does the medical community reach agreement and understanding of the optimal dose and schedule of administration of an agent. For some agents, these conclusions are reached early in the development of the drug (eg, cyclophosphamide, docetaxel). For others (eg, fluorouracil, cytosine arabinoside) the definition of optimal dose and schedule of administration is a never-ending story. The optimal duration of administration for trastuzumab is not known and is currently under active investigation.

Antibodies, Monoclonal↗

PubMed2000

A global optimization strategy for predicting alpha-helical protein tertiary structure.

We present a global optimization strategy that incorporates predicted restraints in both a local optimization context and as directives for global optimization approaches, to predict protein tertiary structure for alpha-helical proteins. Specifically, neural networks are used to predict the secondary structure of a protein, restraints are defined as manifestations of the network with a predicted secondary structure and the secondary structure is formed using local minimizations on a protein energy surface, in the presence of the restraints. Those residues predicted to be coil, by the network, define a conformational sub-space that is subject to optimization using a global approach known as stochastic perturbation that has been found to be effective for Lennard-Jones clusters and homo-polypeptides. Our energy surface is an all-atom 'gas phase' molecular mechanics force field, that is combined with a new solvation energy function that penalizes hydrophobic group exposure. This energy function gives the crystal structure of four different alpha-helical proteins as the lowest energy structure relative to other conformations, with correct secondary structure but incorrect tertiary structure. We demonstrate this global optimization strategy by determining the tertiary structure of the A-chain of the alpha-helical protein, uteroglobin and of a four-helix bundle, DNA binding protein.

Algorithms↗

PubMed2003

Codon optimization of Caenorhabditis elegans GluCl ion channel genes for mammalian cells dramatically improves expression levels.

Organisms use synonymous codons in a highly non-random fashion. These codon usage biases sometimes frustrate attempts to express high levels of exogenous genes in hosts of widely divergent species. The Caenorhabditis elegans GluClalpha1 and GluClbeta genes form a functional glutamate and ivermectin-gated chloride channel when expressed in Xenopus oocytes, but expression is weak in mammalian cells. We have constructed synthetic genes that retain the amino acid sequence of the wild-type GluCl channel proteins, but use codons that are optimal for mammalian cell expression. We have tagged the native and codon-optimized GluCl cDNAs with enhanced yellow fluorescent protein (EYFP, GluClalpha1 subunit) and enhanced cyan fluorescent protein (EFCP, GluClbeta subunit), expressed the channels in E18 rat hippocampal neurons and measured the relative expression levels of the two genes with fluorescence microscopy as well as with electrophysiology. Codon optimization provides a 6- to 9-fold increase in expression, allowing the conclusions that the ivermectin-gated channel has an EC(50) of 1.2 nM and a Hill coefficient of 1.9. We also confirm that the Y182F mutation in the codon-optimized beta subunit results in a heteromeric channel that retains the response to ivermectin while reducing the response to 100 microM glutamate by 7-fold. The engineered GluCl channel is the first codon-optimized membrane protein expressed in mammalian cells and may be useful for selectively silencing specific neuronal populations in vivo.

Animals↗

PubMed2003

Effects of codon-optimization on protein expression by the human herpesvirus 6 and 7 U51 open reading frame.

Codon-optimization refers to the alteration of gene sequences, to make codon usage match the available tRNA pool within the cell/species of interest. Codon-optimization has emerged as a powerful tool to increase protein expression by genes from small RNA and DNA viruses, which commonly contain overlapping reading frames as well as structural elements that are embedded within coding regions; these features are not widespread among large DNA viruses. We therefore examined whether codon-optimization might influence protein expression from a herpesvirus gene. We focused on the U51 gene from human herpesviruses-6 and -7, which was cloned in both native and codon-optimized form, with an N-terminal HA epitope tag to allow protein detection. Codon-optimization was associated with a profound (10-100 fold) increase in U51 expression in human (293A, HSG, K562) or hamster (CHO) cell lines, suggesting this may represent a valuable tool to facilitate functional studies on recalcitrant herpesvirus genes. Finally, it is postulated that the suboptimal expression of native U51 may reflect a regulatory mechanism that controls viral gene expression.

Animals↗

PubMed2001

Beam-orientation optimization of intensity-modulated radiotherapy: clinical application to parotid gland tumours.

BACKGROUND AND PURPOSE: An optimization algorithm has been developed to determine the best beam-arrangement for a small number of intensity-modulated radiotherapy (IMRT) fields. The algorithm is designed to avoid, if possible, beam-orientations that pass through organs-at-risk (OARs) with low radiation tolerance. MATERIALS AND METHODS: An independent, fast IMRT algorithm based on the Bortfeld algorithm was developed to determine the profile of the intensity-modulated beams (IMBs) for each beam-arrangement and a fast-simulated-annealing algorithm finds the 'optimal' beam-arrangement. The final beam-arrangement was transferred to the CORVUS (NOMOS Corporation) treatment planning system, and the IMBs were re-optimized for comparison with a standard nine-field, equi-spaced arrangement. The algorithm has been initially tested on a single example patient, with a parotid gland carcinoma. RESULTS: The nine-field, IMRT plan for an example patient with a parotid gland tumour significantly reduced the dose to the cochlea compared with the conformal radiotherapy plan. In addition, the planning-target-volume (PTV) homogeneity was improved, but the plan produced a higher dose to the contralateral parotid (73% of the OAR received more than 6 Gy). The beam-orientation optimization algorithm produced a three-field plan that greatly reduced the dose to the contralateral parotid (maximum dose of 2 Gy), whilst maintaining the PTV dose homogeneity and the reduced cochlear dose of the nine-field plan. Some changes in the dose to the other OARs, namely the brain and the oral cavity, were seen, but were deemed not to be clinically significant. CONCLUSIONS: In conclusion, IMB-orientation optimization for head and neck treatment sites can produce improvements in treatment plans with only a few fields.

Algorithms↗

PubMed1999

Clinical implementation of wedge filter optimization in three-dimensional radiotherapy treatment planning.

BACKGROUND AND PURPOSE: To describe a wedge filter optimization technique which automatically chooses the beam weights and wedge filters and to demonstrate the implementation of the algorithm in clinical three-dimensional (3D) radiotherapy treatment planning. MATERIAL AND METHODS: Given the incident directions and beam energies of J beams, the dose distribution is a function of the beam weights, wedge angles, and wedge orientations. Instead of decomposing an incident field into a superposition of an open and two nominal wedged fields and then optimizing their weights, the algorithm optimizes the objective function with respect to the beam weights, wedge angles and wedge orientations directly. A salient feature of the algorithm is that no planner intervention was required in the selection of wedge filters during the optimization process. A dose-based objective function which incorporated the relative importance of structures was adopted in this work. The objective function was minimized by the method of simulated annealing. The technique was demonstrated by using a phantom study and two clinical cases. RESULTS: For the phantom case, the classical wedge pair result was obtained, providing a useful test of the algorithm. Dose distributions and dose volume histograms for the target and surrounding organs were presented for the two clinical cases. It was also shown that dose homogeneity to the target could be compromised by increasing the relative importance factors to the surrounding organs. CONCLUSIONS: A 3D wedge filter optimization algorithm has been developed. The technique has the potential to fully automate the 3D radiotherapy treatment planning process. In addition, treatment planning time and efforts were significantly reduced.

Algorithms↗

PubMed2000

Formula optimization of theophylline controlled-release tablet based on artificial neural networks.

Formulation of the controlled-release tablet containing theophylline was optimized based on the simultaneous optimization technique in which an artificial neural network (ANN) was incorporated. As model formulations, 16 kinds of theophylline tablets were prepared. The amounts of Controse, the mixture of hydroxypropylmethyl cellulose with lactose, cornstarch and compression pressure were selected as causal factors. The release profiles of theophylline were characterized as the sum of the fast and slow release fractions. The initial weight, the rate constant in the fast release fraction and the rate constant in the slow release fraction were estimated as release parameters. A set of release parameters and causal factors were used as tutorial data for ANN and analyzed using a computer. Based on the plasma concentration profiles of theophylline predicted by the pharmacokinetic analysis in humans, a desirable set of release parameters was provided. The simultaneous optimization was performed by minimizing the generalized distance between the predicted values of each response and the desirable one that was optimized individually. The optimization technique incorporating ANN showed a fairly good agreement between the observed values of release parameters and the predicted results.

Chemistry, Pharmaceutical↗

PubMed2003

What is the optimal paddle force during paediatric external defibrillation?

INTRODUCTION: Transthoracic impedance (TTI) is a major determinant of transmyocardial current flow, and therefore, the success of defibrillation. European Resuscitation Council (ERC) paediatric guidelines recommend that 'firm' paddle force should be applied to the paddles during defibrillation. No study has yet established the optimal paddle force required to minimise TTI in children of different ages. METHODS: Eighty patients aged 10 weeks to 17 yrs undergoing general anaesthesia for routine surgery were studied. Using defibrillation paddles placed in an anterior-apical position, TTI (Omega) was measured for increasing values of force from 0.5 kgf (baseline) to 6.5 kgf. The optimal force, the force to achieve 95% of the overall reduction in TTI, was then determined. According to current guidelines, paediatric paddles (surface area 16 cm2) were used for infants (< or =10 kg) and adult paddles (82 cm2) for older children. Optimal force was then calculated for infants < or =10 kg, children >10 kg and < or =8 yrs and children 9-17 yrs age. RESULTS: Increasing paddle force from 0.5 kgf progressively decreased TTI. Optimal force using paediatric paddles was 2.9 kgf in infants. Optimal force using adult paddles was 5.1 kgf in children >10 kg but < or = 8 yrs and 5.3 kgf in children aged 9-17 yrs. CONCLUSIONS: Force is an important determinant of TTI and therefore, outcome of defibrillation. It is recommended that a minimum of 3 kgf be applied to paddles when defibrillating infants with paediatric paddles, and a minimum of 5 kgf be applied to all older children when adult paddles are used.

Adolescent↗

PubMed1997

Optimal reductions in CO2 emissions.

Current optimizing climate-economy models use CO2 uptake functions that greatly underestimate both peak atmospheric CO2 concentrations and the time horizon of elevated CO2. As a result these models underestimate potential global warming damages. Here, a more realistic, but practical, carbon cycle parameterization is developed that can be incorporated within an optimizing climate-economy model framework. This method is utilized in conjunction with the DICE model (Nordhaus, 1994) to estimate optimal reductions in CO2 emissions. The results are shown to be extremely sensitive to the pore rate of time preference, rho. For rho=3% (Nordhaus' preferred value), our model predicts an optimal CO2 emission reduction of 13% by the year 2045, as compared to 11% in the original DICE model. But, for rho=0% the optimal emissions reduction rises to 79% in the year 2045 and to 97% by the year 2200. We argue that energy policy should be guided by the rho=0% results for both economic and ethical reasons. A steady-state analysis performed using the DICE model supports the argument that large fractional reductions in CO2 emissions should be undertaken.

Atmosphere↗

PubMed2002

Temporomandibular disorder and optimism: relationships to ischemic pain sensitivity and interleukin-6.

The current study examined patients with temporomandibular disorders (TMD) (n=20) and pain-free controls (n=28) under stress and relaxation conditions. Interleukin-6 (IL-6), norepinephrine and epinephrine (NE and E) were measured both before and during each of two conditions: a non-stressful relaxation period and a speech stressor. Ischemic pain sensitivity was also assessed after each of these conditions. Optimism (Life Orientation Test (LOT)), which has been associated with better outcomes in relationship to health and disease, was also evaluated in relationship to ischemic pain tolerance and unpleasantness ratings as well as to IL-6 levels under the two conditions. Regression analysis determined the unique contribution of each predictor and the interaction between Optimism and Group (TMD versus controls) after controlling for gender and blood pressure. During stress, IL-6 levels appeared to parallel NE with only controls displaying significant increases. After controlling for depressed mood, TMD patients as a whole showed a significantly blunted response in IL-6 levels produced during stress as compared to controls (beta=0.31*). Although TMD subjects as a whole did not show the expected greater pain sensitivity to the ischemic task, those displaying a less optimistic style did exhibit lower pain tolerance times (beta=-0.61*) and higher pain unpleasantness ratings (beta=0.48*), compared with low optimism controls and high optimism TMD patients. Less optimistic TMD patients also had higher NE and IL-6 levels during stress than other TMD patients, while optimism was unrelated to responses in controls (*P<0.05).

Adult↗

PubMed2000

Optimizing radiotherapy of orbital and paraorbital tumors: intensity-modulated X-ray beams vs. intensity-modulated proton beams.

PURPOSE: This study presents a dosimetric optimization effort aiming to compare intensity-modulated (IM) X-rays and IM protons in 4 different orbital and paraorbital tumors. These are most challenging targets for standard radiotherapy due to their close relationship with the eyes and related structures. METHODS AND MATERIALS: A primary orbital lymphoma, an optic nerve meningioma, a sphenoidal ridge meningioma protruding into the orbit, and a pediatric parameningeal paraorbital rhabdomyosarcoma were selected for the purpose of this study. Planning target volumes (PTVs) and organs at risk (OAR) were defined in each patient CT data set for each tumor site. IM X-ray and IM proton three-dimensional treatment plans were implemented. The following total tumor doses were prescribed: 30 Gy for the orbital lymphoma, 54 Gy for both meningiomas, and 50.4 Gy for the rhabdomyosarcoma case. Dose-volume histograms (DVHs) were obtained for all targets and OAR with both treatment techniques. DVHs were used to predict normal tissue complication probabilities (NTCPs) for the OAR in the vicinity of the tumor. RESULTS: The PTV coverage was optimal and equally homogeneous with both IM X-rays and IM proton plans in the 4 tumor sites. DVHs for most OAR were better with IM proton beams especially in the low- to mid-dose range region. The integral nontarget dose was lower with IM protons in every case (factor ranging from 1.5 to 1.9). However, predicted NTCPs (for severe late effects) were equally low for both treatment techniques in every tumor site. CONCLUSION: Although IM proton plans optimally decreased the dose to the OAR in all tumor sites, both optimized X-ray and proton beams equally succeeded to reduce severe-toxicity prediction risks to less than 5% while optimally treating the PTV.

Humans↗

PubMed2000

Postimplantation dosimetric analysis of permanent transperineal prostate implantation: improved dose distributions with an intraoperative computer-optimized conformal planning technique.

PURPOSE: To compare the target coverage and dose to normal tissues after I-125 transperineal permanent implantation (TPI) of the prostate in 90 patients treated with one of three different transperineal techniques. METHODS AND MATERIALS: Detailed postimplant dosimetric evaluations of permanent I-125 implantation procedures were performed on 30 consecutive patients treated between 1995-1996 who underwent TPI using a preplanning CT-based technique, on 30 consecutive patients treated in 1997-1998 who underwent an ultrasound-guided approach with intraoperative determination of seed distribution based on an I-125 nomogram, and on 30 consecutive patients in 1998-1999 who underwent TPI with intraoperative computer-based 3-dimensional conformal optimization. For all three techniques, postimplant CT scans were obtained 4-6 hours after TPI. Dosimetric parameters included V(100), V(90), V(150), D(100), D(90), D(80), as well as maximal and average doses to the urethra and rectal wall. These parameter outcomes are reported as a percentage of the prescription dose. RESULTS: The intraoperative 3D-optimized technique (I-3D) provided superior target coverage with the prescription dose for all dosimetric variables evaluated compared to the other treatment techniques. The median V(100), V(90), and D(90) values for the I-3D technique were 96%, 98%, and 116%, respectively. In contrast, the V(100), V(90), and D(90) values for the CT preplan and ultrasound manual optimization approaches were 86%, 89%, and 88%, respectively and 88%, 92%, and 94%, respectively (I-3D versus other techniques: p < 0.001). The superior target coverage with the I-3D technique was also associated with a higher cumulative implant activity required by the optimization program. A multivariate analysis determined that the treatment technique (I-3D versus other approaches) was an independent predictor of improved target coverage for each parameter analyzed (p < 0.001). In addition, higher cumulative implant activities and smaller prostate target volumes were independent predictors of improved target coverage. The maximum and average urethral doses were significantly lower with the I-3D technique compared to the other techniques; a modest increase in the average rectal dose was also observed with this approach. CONCLUSION: Three-dimensional intraoperative computer optimized TPI consistently provided superior target coverage with the prescription dose and significantly lower urethral doses compared to two other techniques used. These data provide proof-of-principle that improved therapeutic ratios can be achieved with the integration of more sophisticated intraoperative planning for TPI and may potentially have a profound impact on the outcome of patients treated with this modality.

Algorithms↗

PubMed2002

Optimization of intensity-modulated radiotherapy plans based on the equivalent uniform dose.

PURPOSE: The equivalent uniform dose (EUD) for tumors is defined as the biologically equivalent dose that, if given uniformly, will lead to the same cell kill in the tumor volume as the actual nonuniform dose distribution. Recently, a new formulation of EUD was introduced that applies to normal tissues as well. EUD can be a useful end point in evaluating treatment plans with nonuniform dose distributions for three-dimensional conformal radiotherapy and intensity-modulated radiotherapy. In this study, we introduce an objective function based on the EUD and investigate the feasibility and usefulness of using it for intensity-modulated radiotherapy optimization. METHODS AND MATERIALS: We applied the EUD-based optimization to obtain intensity-modulated radiotherapy plans for prostate and head-and-neck cancer patients and compared them with the corresponding plans optimized with dose-volume-based criteria. RESULTS: We found that, for the same or better target coverage, EUD-based optimization is capable of improving the sparing of critical structures beyond the specified requirements. We also found that, in the absence of constraints on the maximal target dose, the target dose distributions are more inhomogeneous, with significant hot spots within the target volume. This is an obvious consequence of unrestricted maximization target cell kill and, although this may be considered beneficial for some cases, it is generally not desirable. To minimize the magnitude of hot spots, we applied dose inhomogeneity constraints to the target by treating it as a "virtual" normal structure as well. This led to much-improved target dose homogeneity, with a small, but expected, degradation in normal structure sparing. We also found that, in principle, the dose-volume objective function may be able to arrive at similar optimum dose distributions by using multiple dose-volume constraints for each anatomic structure and with considerably greater trial-and-error to adjust a large number of objective function parameters. CONCLUSION: The general inference drawn from our investigation is that the EUD-based objective function has the advantages that it needs only a small number of parameters and allows exploration of a much larger universe of solutions, making it easier for the optimization system to balance competing requirements in search of a better solution.

Algorithms↗

PubMed2004

Optimization of MammoSite therapy.

PURPOSE: Radiation source anisotropy causes about 10% of a spherically shaped planning target volume surrounding a MammoSite balloon to receive less than the prescribed dose. The principal dose-limiting factor for MammoSite therapy is the dose to the overlying skin. Additional limiting factors potentially include the dose to portions of the heart and lung. The goal of optimization is to deliver the prescribed dose to as much of the planning target volume as possible while avoiding toxicity to adjacent organs. METHODS AND MATERIALS: An experimental CT-based high-dose-rate brachytherapy treatment planning system was used to investigate optimization strategies for MammoSite treatment. This system implements a linear optimization of high-dose-rate dwell times on the basis of constraints assigned to points of interest and a set of potential dwell positions. RESULTS: The cylindrical symmetry of the MammoSite catheter limits the optimization process to creating spherical, ellipsoidal, or egg-shaped isodose distributions whose major axis is oriented along the catheter axis. If the dose to a limiting structure, such as skin, is not an issue, the use of multiple dwell positions can compensate for source anisotropy and create a more spherical isodose surface enclosing the planning target volume compared with a single dwell position. When skin becomes a dose-limiting factor, the catheter axis orientation, source anisotropy, dwell position, and dwell weighting can be exploited to limit the skin dose while simultaneously preserving the prescribed dose to as much of the target volume as possible. CONCLUSION: Optimization of MammoSite therapy using multiple dwell positions within the balloon is both possible and practical.

Anisotropy↗