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Pencil-beam redefinition algorithm for electron dose distributions.

A pencil-beam redefinition algorithm has been developed for the calculation of electron-beam dose distributions on a three-dimensional grid utilizing 3-D inhomogeneity correction. The concept of redefinition was first used for both fixed and arced electron beams by Hogstrom et al. but was limited to a single redefinition. The success of those works stimulated the development of the pencil-beam redefinition algorithm, the aim of which is to solve the dosimetry problems presented by deep inhomogeneities through development of a model that redefines the pencil beams continuously with depth. This type of algorithm was developed independently by Storchi and Huizenga who termed it the "moments method." Such a pencil beam within the patient is characterized by a complex angular distribution, which is approximated by a Gaussian distribution having the same first three moments as the actual distribution. Three physical quantities required for dose calculation and subsequent radiation transport--namely planar fluence, mean direction, and root-mean-square spread about the mean direction--are obtained from these moments. The primary difference between the moments method and the redefinition algorithm is that the latter subdivides the pencil beams into multiple energy bins. The algorithm then becomes a macroscopic method for transporting the complete phase space of the beam and allows the calculation of physical quantities such as fluence, dose, and energy distribution. Comparison of calculated dose distributions with measured dose distributions for a homogeneous water phantom, and for phantoms with inhomogeneities deep relative to the surface, show agreement superior to that achieved with the pencil-beam algorithm of Hogstrom et al. in the penumbral region and beneath the edges of air and bone inhomogeneities. The accuracy of the redefinition algorithm is within 4% and appears sufficient for clinical use, and the algorithm is structured for further expansion of the physical model if required for site-specific treatment planning problems.

Algorithms↗

Improving the convergence of iterative filtered backprojection algorithms.

Several authors have proposed variations of the iterative filtered backprojection (IFBP) reconstruction algorithms claiming fast initial convergence rates. We have found that these algorithms are trying to minimize an unusual squared-error criterion in a suboptimal way. As a result, existing IFBP algorithms are inefficient in the minimization of the criterion, and may become unstable at higher iteration numbers. We show that existing IFBP algorithms can be modified to use the steepest descent technique by simply optimizing the step size at each iteration. Further gains in convergence rates can be achieved with conjugate gradient IFBP algorithms derived from the same criterion. The steepest descent and conjugate gradient IFBP algorithms are guaranteed to converge, unlike some IFBP algorithms, and will do so in fewer iterations than existing IFBP algorithms.

Algorithms↗

A fast and stable maximum a posteriori conjugate gradient reconstruction algorithm.

We have derived a maximum a posteriori (MAP) approach for iterative reconstruction based on a weighted least-squares conjugate gradient (WLS-CG) algorithm. The WLS-CG algorithm has been shown to have initial convergence rates up to 10x faster than the maximum-likelihood expectation maximization (ML-EM) algorithm, but WLS-CG suffers from rapidly increasing image noise at higher iteration numbers. In our MAP-CG algorithm, the increasing noise is controlled by a Gibbs smoothing prior, resulting in stable, convergent solutions. Our formulation assumes a Gaussian noise model for the likelihood function. When a linear transformation of the pixel space is performed (the "relaxation" acceleration method), the MAP-CG algorithm obtains a low-noise, stable solution (one that does not change with further iterations) in 10-30 iterations, compared to 100-200 iterations for MAP-EM. Each iteration of MAP-CG requires approximately the same amount of processing time as one iteration of ML-EM or MAP-EM. We show that the use of an initial image estimate obtained from a single iteration of the Chang method helps the algorithm to converge faster when acceleration is not used, but does not help when acceleration is applied. While both the WLS-CG and MAP-CG methods suffer from the potential for obtaining negative pixel values in the iterated image estimates, the use of the Gibbs prior substantially reduces the number of pixels with negative values and restricts them to regions of little or no activity. We use SPECT data from simulated hot-sphere phantoms and from patient studies to demonstrate the advantages of the MAP-CG algorithm. We conclude that the MAP-CG algorithm requires 10%-25% of the processing time of EM techniques, and provides images of comparable or superior quality.

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A computational algorithm for computing nonlinear auditory frequency selectivity.

Computational algorithms that mimic the response of the basilar membrane must be capable of reproducing a range of complex features that are characteristic of the animal observations. These include complex input output functions that are nonlinear near the site's best frequency, but linear elsewhere. This nonlinearity is critical when using the output of the algorithm as the input to models of inner hair cell function and subsequent auditory-nerve models of low- and high-spontaneous rate fibers. We present an algorithm that uses two processing units operating in parallel: one linear and the other compressively nonlinear. The output from the algorithm is the sum of the outputs of the linear and nonlinear processing units. Input to the algorithm is stapes motion and output represents basilar membrane motion. The algorithm is evaluated against published chinchilla and guinea pig observations of basilar membrane and Reissner's membrane motion made using laser velocimetry. The algorithm simulates both quantitatively and qualitatively, differences in input/output functions among three different sites along the cochlear partition. It also simulates quantitatively and qualitatively a range of phenomena including isovelocity functions, phase response, two-tone suppression, impulse response, and distortion products. The algorithm is potentially suitable for development as a bank of filters, for use in more comprehensive models of the peripheral auditory system.

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Case finding for patients at risk of readmission to hospital: development of algorithm to identify high risk patients.

OBJECTIVE: To develop a method of identifying patients at high risk of readmission to hospital in the next 12 months for practical use by primary care trusts and general practices in the NHS in England. DATA SOURCES: Data from hospital episode statistics showing all admissions in NHS trusts in England over five years, 1999-2000 to 2003-4; data from the 2001 census for England. Population All residents in England admitted to hospital in the previous four years with a subset of "reference" conditions for which improved management may help to prevent future admissions. DESIGN: Multivariate statistical analysis of routinely collected data to develop an algorithm to predict patients at highest risk of readmission in the next 12 months. The algorithm was developed by using a 10% sample of hospital episode statistics data for all of England for the period indicated. The coefficients for 21 most powerful (and statistically significant) variables were then applied against a second 10% test sample to validate the findings of the algorithm from the first sample. RESULTS: The key factors predicting subsequent admission included age, sex, ethnicity, number of previous admissions, and clinical condition. The algorithm produces a risk score (from 0 to 100) for each patient admitted with a reference condition. At a risk score threshold of 50, the algorithm identified 54.3% of patients admitted with a reference condition who would have an admission in the next 12 months; 34.7% of patients were "flagged" incorrectly (they would not have a subsequent admission). At risk score threshold levels of 70 and 80, the rate of incorrectly "flagged" patients dropped to 22.6% and 15.7%, but the algorithm found a lower percentage of patients who would be readmitted. The algorithm is made freely available to primary care trusts via a website. CONCLUSIONS: A method of predicting individual patients at highest risk of readmission to hospital in the next 12 months has been developed, which has a reasonable level of sensitivity and specificity. Using various assumptions a "business case" has been modelled to demonstrate to primary care trusts and practices the potential costs and impact of an intervention using the algorithm to reduce hospital admissions.

Aged↗

Randomized algorithms for motif detection.

MOTIVATION: Motif detection for DNA sequences has many important applications in biological studies, e.g. locating binding sites regulatory signals, designing genetic probes etc. In this paper, we propose a randomized algorithm, design an improved EM algorithm and combine them to form a software tool. RESULTS: (1) We design a randomized algorithm for consensus pattern problem. We can show that with high probability, our randomized algorithm finds a pattern in polynomial time with cost error at most x l for each string, where l is the length of the motif and can be any positive number given by the user. (2) We design an improved EM algorithm that outperforms the original EM algorithm. (3) We develop a software tool, MotifDetector, that uses our randomized algorithm to find good seeds and uses the improved EM algorithm to do local search. We compare MotifDetector with Buhler and Tompa's PROJECTION which is considered to be the best known software for motif detection. Simulations show that MotifDetector is slower than PROJECTION when the pattern length is relatively small, and outperforms PROJECTION when the pattern length becomes large. AVAILABILITY: It is available for free at http://www.cs.cityu.edu.hk/~lwang/software/motif/index.html, subject to copyright restrictions.

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Emphysema: effect of reconstruction algorithm on CT imaging measures.

In the current study, the effects of reconstruction algorithms on quantitative measures derived from computed tomographic (CT) lung images were assessed in patients with emphysema. CT image data sets were reconstructed with a standard algorithm and alternative algorithm(s) for 42 subjects. Algorithms were grouped as overenhancing, sharp, standard, or smooth. Density mask and volume measurements from the alternative algorithm data sets were compared with standard algorithm data sets. The overenhancing category yielded an average shift of 9.4% (ie, a shift in average score from 35.5% to 44.9%); the sharp category, a shift of 2.4%; and the smooth category, a shift of -1.0%. Differences in total lung volume measurements were less than 1%. In conclusion, the CT reconstruction algorithm may strongly affect density mask results, especially for certain reconstruction algorithms.

Aged↗

Comparison of information-preserving and information-losing data-compression algorithms for CT images.

Data compression increases the number of images that can be stored on magnetic disks or tape and reduces the time required for transmission of images between stations. Two algorithms for data compression are compared in application to computed tomographic (CT) images. The first, an information-preserving algorithm combining differential and Huffman encoding, allows reconstruction of the original image. A second algorithm alters the image in a clinically acceptable manner. This second algorithm combines two processes: the suppression of data outside of the head or body and the combination of differential and Huffman encoding. Because the final image is not an exact copy, the second algorithm is information losing. Application of the information-preserving algorithm can double or triple the number of CT images that can be stored on hard disk or magnetic tape. This algorithm may also double or triple the speed with which images may be transmitted. The information-losing algorithm can increase storage or transmission speed by a factor of five. The computation time on this system is excessive, but dedicated hardware is available to allow efficient implementation.

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Selectivity of inferior temporal neurons for realistic pictures predicted by algorithms for image database navigation.

Primates have a remarkable ability to perceive, recognize, and discriminate among the plethora of people, places, and things that they see, and neural selectivity in the primate inferotemporal (IT) cortex is thought to underlie this ability. Here we investigated the relationship between neural response and perception by recording from IT neurons in monkeys while they viewed realistic images. We then compared the similarity of neural responses elicited by images to the quantitative similarity of the images. Image similarity was approximated using several algorithms, two of which were designed to search image databases for perceptually similar images. Some algorithms for image similarity correlated well with human perception, and these algorithms explained part of the stimulus selectivity of IT neurons. Images that elicited similar neural responses were ranked as more similar by these algorithms than images that elicited different neural responses, and images ranked as similar by the algorithms elicited similar responses from neurons. Neural selectivity was predicted more accurately when the reference images for algorithm similarity elicited either very strong or very weak responses from the neuron. The degree to which algorithms for image similarity were correlated with human perception was related to the degree to which algorithms explained the selectivity of IT neurons, providing support for the proposal that the selectivity of IT neurons is related to perceptual similarity of images.

Action Potentials↗

A parallel noise-robust algorithm to recover depth information from radial flow fields.

A parallel algorithm operating on the units ('neurons') of an artificial retina is proposed to recover depth information in a visual scene from radial flow fields induced by ego motion along a given axis. The system consists of up to 600 radii with fewer than 65 radially arranged neurons on each radius. Neurons are connected only to their nearest neighbors, and they are excited as soon as a sufficiently strong gray-level change occurs. The time difference of two subsequently activated neurons is then used by the last-excited neuron to compute the depth information. All algorithmic calculations remain strictly local, and information is exchanged only between adjacent active neurons (except for the final read-out). This, in principle, permits parallel implementation. Furthermore, it is demonstrated that the calculation of the object coordinates requires only a single multiplication with a constant, which is dependent on only the retinal position of the active neuron. The initial restriction to local operations makes the algorithm very noise sensitive. In order to solve this problem, a predication mechanism is introduced. After an object coordinate has been determined, the active neuron computes the time when the next neuronal excitation should take place. This estimated time is transferred to the respective next neuron, which will wait for this excitation only within a certain time window. If the excitation fails to arrive within this window, the previously computed object coordinate is regarded as noisy and discarded. We will show that this predictive mechanism relies also on only a (second) single multiplication with another neuron-dependent constant. Thus, computational complexity remains low, and noisy depth coordinates are efficiently eliminated. Thus, the algorithm is very fast and operates in real time on 128 x 128 images even in a serial implementation on a relatively slow computer. The algorithm is tested on scenes of growing complexity, and a detailed error analysis is provided showing that the depth error remains very low in most cases. A comparison to standard flow-field analysis shows that our algorithm outperforms the older method by far. The analysis of the algorithm also shows that it is generally applicable despite its restrictions, because it is fast and accurate enough such that a complete depth percept can be composed from radial flow field segments. Finally, we suggest how to generalize the algorithm, waiving the restriction of radial flow.

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Performance of a genetic algorithm for mass spectrometry proteomics.

BACKGROUND: Recently, mass spectrometry data have been mined using a genetic algorithm to produce discriminatory models that distinguish healthy individuals from those with cancer. This algorithm is the basis for claims of 100% sensitivity and specificity in two related publicly available datasets. To date, no detailed attempts have been made to explore the properties of this genetic algorithm within proteomic applications. Here the algorithm's performance on these datasets is evaluated relative to other methods. RESULTS: In reproducing the method, some modifications of the algorithm as it is described are necessary to get good performance. After modification, a cross-validation approach to model selection is used. The overall classification accuracy is comparable though not superior to other approaches considered. Also, some aspects of the process rely upon random sampling and thus for a fixed dataset the algorithm can produce many different models. This raises questions about how to choose among competing models. How this choice is made is important for interpreting sensitivity and specificity results as merely choosing the model with lowest test set error rate leads to overestimates of model performance. CONCLUSIONS: The algorithm needs to be modified to reduce variability and care must be taken in how to choose among competing models. Results derived from this algorithm must be accompanied by a full description of model selection procedures to give confidence that the reported accuracy is not overstated.

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GenClust: a genetic algorithm for clustering gene expression data.

BACKGROUND: Clustering is a key step in the analysis of gene expression data, and in fact, many classical clustering algorithms are used, or more innovative ones have been designed and validated for the task. Despite the widespread use of artificial intelligence techniques in bioinformatics and, more generally, data analysis, there are very few clustering algorithms based on the genetic paradigm, yet that paradigm has great potential in finding good heuristic solutions to a difficult optimization problem such as clustering. RESULTS: GenClust is a new genetic algorithm for clustering gene expression data. It has two key features: (a) a novel coding of the search space that is simple, compact and easy to update; (b) it can be used naturally in conjunction with data driven internal validation methods. We have experimented with the FOM methodology, specifically conceived for validating clusters of gene expression data. The validity of GenClust has been assessed experimentally on real data sets, both with the use of validation measures and in comparison with other algorithms, i.e., Average Link, Cast, Click and K-means. CONCLUSION: Experiments show that none of the algorithms we have used is markedly superior to the others across data sets and validation measures; i.e., in many cases the observed differences between the worst and best performing algorithm may be statistically insignificant and they could be considered equivalent. However, there are cases in which an algorithm may be better than others and therefore worthwhile. In particular, experiments for GenClust show that, although simple in its data representation, it converges very rapidly to a local optimum and that its ability to identify meaningful clusters is comparable, and sometimes superior, to that of more sophisticated algorithms. In addition, it is well suited for use in conjunction with data driven internal validation measures and, in particular, the FOM methodology.

Algorithms↗

Utilization of two sample t-test statistics from redundant probe sets to evaluate different probe set algorithms in GeneChip studies.

BACKGROUND: The choice of probe set algorithms for expression summary in a GeneChip study has a great impact on subsequent gene expression data analysis. Spiked-in cRNAs with known concentration are often used to assess the relative performance of probe set algorithms. Given the fact that the spiked-in cRNAs do not represent endogenously expressed genes in experiments, it becomes increasingly important to have methods to study whether a particular probe set algorithm is more appropriate for a specific dataset, without using such external reference data. RESULTS: We propose the use of the probe set redundancy feature for evaluating the performance of probe set algorithms, and have presented three approaches for analyzing data variance and result bias using two sample t-test statistics from redundant probe sets. These approaches are as follows: 1) analyzing redundant probe set variance based on t-statistic rank order, 2) computing correlation of t-statistics between redundant probe sets, and 3) analyzing the co-occurrence of replicate redundant probe sets representing differentially expressed genes. We applied these approaches to expression summary data generated from three datasets utilizing individual probe set algorithms of MAS5.0, dChip, or RMA. We also utilized combinations of options from the three probe set algorithms. We found that results from the three approaches were similar within each individual expression summary dataset, and were also in good agreement with previously reported findings by others. We also demonstrate the validity of our findings by independent experimental methods. CONCLUSION: All three proposed approaches allowed us to assess the performance of probe set algorithms using the probe set redundancy feature. The analyses of redundant probe set variance based on t-statistic rank order and correlation of t-statistics between redundant probe sets provide useful tools for data variance analysis, and the co-occurrence of replicate redundant probe sets representing differentially expressed genes allows estimation of result bias. The results also suggest that individual probe set algorithms have dataset-specific performance.

Algorithms↗

Probe set algorithms: is there a rational best bet?

Affymetrix microarrays have become a standard experimental platform for studies of mRNA expression profiling. Their success is due, in part, to the multiple oligonucleotide features (probes) against each transcript (probe set). This multiple testing allows for more robust background assessments and gene expression measures, and has permitted the development of many computational methods to translate image data into a single normalized "signal" for mRNA transcript abundance. There are now many probe set algorithms that have been developed, with a gradual movement away from chip-by-chip methods (MAS5), to project-based model-fitting methods (dCHIP, RMA, others). Data interpretation is often profoundly changed by choice of algorithm, with disoriented biologists questioning what the "accurate" interpretation of their experiment is. Here, we summarize the debate concerning probe set algorithms. We provide examples of how changes in mismatch weight, normalizations, and construction of expression ratios each dramatically change data interpretation. All interpretations can be considered as computationally appropriate, but with varying biological credibility. We also illustrate the performance of two new hybrid algorithms (PLIER, GC-RMA) relative to more traditional algorithms (dCHIP, MAS5, Probe Profiler PCA, RMA) using an interactive power analysis tool. PLIER appears superior to other algorithms in avoiding false positives with poorly performing probe sets. Based on our interpretation of the literature, and examples presented here, we suggest that the variability in performance of probe set algorithms is more dependent upon assumptions regarding "background", than on calculations of "signal". We argue that "background" is an enormously complex variable that can only be vaguely quantified, and thus the "best" probe set algorithm will vary from project to project.

Algorithms↗

Evaluation of clustering algorithms for gene expression data.

BACKGROUND: Cluster analysis is an integral part of high dimensional data analysis. In the context of large scale gene expression data, a filtered set of genes are grouped together according to their expression profiles using one of numerous clustering algorithms that exist in the statistics and machine learning literature. A closely related problem is that of selecting a clustering algorithm that is "optimal" in some sense from a rather impressive list of clustering algorithms that currently exist. RESULTS: In this paper, we propose two validation measures each with two parts: one measuring the statistical consistency (stability) of the clusters produced and the other representing their biological functional congruence. Smaller values of these indices indicate better performance for a clustering algorithm. We illustrate this approach using two case studies with publicly available gene expression data sets: one involving a SAGE data of breast cancer patients and the other involving a time course cDNA microarray data on yeast. Six well known clustering algorithms UPGMA, K-Means, Diana, Fanny, Model-Based and SOM were evaluated. CONCLUSION: No single clustering algorithm may be best suited for clustering genes into functional groups via expression profiles for all data sets. The validation measures introduced in this paper can aid in the selection of an optimal algorithm, for a given data set, from a collection of available clustering algorithms.

Algorithms↗

Algorithm for identifying and separating beats from arterial pulse records.

BACKGROUND: This project was designed as an epidemiological aid-selecting tool for a small country health center with the general objective of screening out possible coronary patients. Peripheral artery function can be non-invasively evaluated by impedance plethysmography. Changes in these vessels appear as good predictors of future coronary behavior. Impedance plethysmography detects volume variations after simple occlusive maneuvers that may show indicative modifications in arterial/venous responses. Averaging of a series of pulses is needed and this, in turn, requires proper determination of the beginning and end of each beat. Thus, the objective here is to describe an algorithm to identify and separate out beats from a plethysmographic record. A secondary objective was to compare the output given by human operators against the algorithm. METHODS: The identification algorithm detected the beat's onset and end on the basis of the maximum rising phase, the choice of possible ventricular systolic starting points considering cardiac frequency, and the adjustment of some tolerance values to optimize the behavior. Out of 800 patients in the study, 40 occlusive records (supradiastolic- subsystolic) were randomly selected without any preliminary diagnosis. Radial impedance plethysmographic pulse and standard ECG were recorded digitizing and storing the data. Cardiac frequency was estimated with the Power Density Function and, thereafter, the signal was derived twice, followed by binarization of the first derivative and rectification of the second derivative. The product of the two latter results led to a weighing signal from which the cycles' onsets and ends were established. Weighed and frequency filters are needed along with the pre-establishment of their respective tolerances. Out of the 40 records, 30 seconds strands were randomly chosen to be analyzed by the algorithm and by two operators. Sensitivity and accuracy were calculated by means of the true/false and positive/negative criteria. Synchronization ability was measured through the coefficient of variation and the median value of correlation for each patient. These parameters were assessed by means of Friedman's ANOVA and Kendall Concordance test. RESULTS: Sensitivity was 97% and 91% for the two operators, respectively, while accuracy was cero for both of them. The synchronism variability analysis was significant (p < 0.01) for the two statistics, showing that the algorithm produced the best result. CONCLUSION: The proposed algorithm showed good performance as expressed by its high sensitivity. The correlation analysis demonstrated that, from the synchronism point of view, the algorithm performed the best detection. Patients with marked arrhythmic processes are not good candidates for this kind of analysis. At most, they would be singled out by the algorithm and, thereafter, to be checked by an operator.

Algorithms↗

Reliability of old and new ventricular fibrillation detection algorithms for automated external defibrillators.

BACKGROUND: A pivotal component in automated external defibrillators (AEDs) is the detection of ventricular fibrillation by means of appropriate detection algorithms. In scientific literature there exists a wide variety of methods and ideas for handling this task. These algorithms should have a high detection quality, be easily implementable, and work in real time in an AED. Testing of these algorithms should be done by using a large amount of annotated data under equal conditions. METHODS: For our investigation we simulated a continuous analysis by selecting the data in steps of one second without any preselection. We used the complete BIH-MIT arrhythmia database, the CU database, and the files 7001-8210 of the AHA database. All algorithms were tested under equal conditions. RESULTS: For 5 well-known standard and 5 new ventricular fibrillation detection algorithms we calculated the sensitivity, specificity, and the area under their receiver operating characteristic. In addition, two QRS detection algorithms were included. These results are based on approximately 330,000 decisions (per algorithm). CONCLUSION: Our values for sensitivity and specificity differ from earlier investigations since we used no preselection. The best algorithm is a new one, presented here for the first time.

Algorithms↗

Optimization of extracranial stereotactic radiation therapy of small lung lesions using accurate dose calculation algorithms.

BACKGROUND: The aim of this study was to compare and to validate different dose calculation algorithms for the use in radiation therapy of small lung lesions and to optimize the treatment planning using accurate dose calculation algorithms. METHODS: A 9-field conformal treatment plan was generated on an inhomogeneous phantom with lung mimics and a soft tissue equivalent insert, mimicking a lung tumor. The dose distribution was calculated with the Pencil Beam and Collapsed Cone algorithms implemented in Masterplan (Nucletron) and the Monte Carlo system XVMC and validated using Gafchromic EBT films. Differences in dose distribution were evaluated. The plans were then optimized by adding segments to the outer shell of the target in order to increase the dose near the interface to the lung. RESULTS: The Pencil Beam algorithm overestimated the dose by up to 15% compared to the measurements. Collapsed Cone and Monte Carlo predicted the dose more accurately with a maximum difference of -8% and -3% respectively compared to the film. Plan optimization by adding small segments to the peripheral parts of the target, creating a 2-step fluence modulation, allowed to increase target coverage and homogeneity as compared to the uncorrected 9 field plan. CONCLUSION: The use of forward 2-step fluence modulation in radiotherapy of small lung lesions allows the improvement of tumor coverage and dose homogeneity as compared to non-modulated treatment plans and may thus help to increase the local tumor control probability. While the Collapsed Cone algorithm is closer to measurements than the Pencil Beam algorithm, both algorithms are limited at tissue/lung interfaces, leaving Monte-Carlo the most accurate algorithm for dose prediction.

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