Volume and dose-response effects for severe symptomatic pneumonitis after fractionated irradiation of canine lung.

PURPOSE: To study the dose-related incidence of severe symptomatic pneumonitis following fractionated irradiation applied to three different volumes of lung in normal beagle dogs. MATERIALS AND METHODS: A three-dimensional treatment planning system was used to design mediastinal fields of increasing width to irradiate 33%, 67% or 100% of both lungs combined in 128 normal beagle dogs. Total doses, ranging from 27 to 72 Gy, were delivered in 1.5 Gy fractions over 6 weeks. RESULTS: No dogs irradiated to 33% of their total lung volume developed severe symptomatic pneumonitis. In the 67% volume group, logistic fit of the data showed a dose-response curve with a 50% probability of developing severe symptomatic pneumonitis (ED50) after a total dose of 56.0 Gy (52.2-66.0 Gy, 95% confidence interval, CI). The more clinically relevant ED5 for the first 6 months after irradiation of 67% of the lung was 48.1 Gy (18.5-52.0 Gy, 95% CI). The ED50 and ED5 values after irradiation of the whole lung (100%) were 44.1 Gy (41.2-53.5Gy, 95% CI) and 39.1 Gy (8.8-41.8 Gy, 95% CI) respectively. CONCLUSION: Severe symptomatic pneumonitis proved to be a very informative volume-effect endpoint, clearly demonstrating that irradiated lung volume is a critical parameter to be considered in assigning thoracic radiotherapy treatment parameters. Volume effects in lung are dependent on the compensatory capacity of the nonirradiated lung. Underlying pathophysiology of irradiated tissue, as well as decreased compensatory capacity of nonirradiated tissue may have a strong effect on the dose-volume response.

Comparison of computer workstation with light box for detecting setup errors from portal images.

PURPOSE: Observer studies were conducted to test the hypothesis that radiation oncologists using a computer workstation for portal image analysis can detect setup errors at least as accurately as when following standard clinical practice of inspecting portal films on a light box. METHODS AND MATERIALS: In a controlled observer study, nine radiation oncologists used a computer workstation, called PortFolio, to detect setup errors in 40 realistic digitally reconstructed portal radiograph (DRPR) images. PortFolio is a prototype workstation for radiation oncologists to display and inspect digital portal images for setup errors. PortFolio includes tools for image enhancement; alignment of crosshairs, field edges, and anatomic structures on reference and acquired images; measurement of distances and angles; and viewing registered images superimposed on one another. The test DRPRs contained known in-plane translation or rotation errors in the placement of the fields over target regions in the pelvis and head. Test images used in the study were also printed on film for observers to view on a light box and interpret using standard clinical practice. The mean accuracy for error detection for each approach was measured and the results were compared using repeated measures analysis of variance (ANOVA) with the Geisser-Greenhouse test statistic. RESULTS: The results indicate that radiation oncologists participating in this study could detect and quantify in-plane rotation and translation errors more accurately with PortFolio compared to standard clinical practice. CONCLUSIONS: Based on the results of this limited study, it is reasonable to conclude that workstations similar to PortFolio can be used efficaciously in clinical practice.

Segmentation, registration, and measurement of shape variation via image object shape.

A model of object shape by nets of medial and boundary primitives is justified as richly capturing multiple aspects of shape and yet requiring representation space and image analysis work proportional to the number of primitives. Metrics are described that compute an object representation's prior probability of local geometry by reflecting variabilities in the net's node and link parameter values, and that compute a likelihood function measuring the degree of match of an image to that object representation. A paradigm for image analysis of deforming such a model to optimize a posteriori probability is described, and this paradigm is shown to be usable as a uniform approach for object definition, object-based registration between images of the same or different imaging modalities, and measurement of shape variation of an abnormal anatomical object, compared with a normal anatomical object. Examples of applications of these methods in radiotherapy, surgery, and psychiatry are given.

Portfolio: a prototype workstation for development and evaluation of tools for analysis and management of digital portal images.

PURPOSE: The purpose of this investigation was to design and implement a prototype physician workstation, called PortFolio, as a platform for developing and evaluating, by means of controlled observer studies, user interfaces and interactive tools for analyzing and managing digital portal images. The first observer study was designed to measure physician acceptance of workstation technology, as an alternative to a view box, for inspection and analysis of portal images for detection of treatment setup errors. METHODS AND MATERIALS: The observer study was conducted in a controlled experimental setting to evaluate physician acceptance of the prototype workstation technology exemplified by PortFolio. PortFolio incorporates a windows user interface, a compact kit of carefully selected image analysis tools, and an object-oriented data base infrastructure. The kit evaluated in the observer study included tools for contrast enhancement, registration, and multimodal image visualization. Acceptance was measured in the context of performing portal image analysis in a structured protocol designed to simulate clinical practice. The acceptability and usage patterns were measured from semistructured questionnaires and logs of user interactions. RESULTS: Radiation oncologists, the subjects for this study, perceived the tools in PortFolio to be acceptable clinical aids. Concerns were expressed regarding user efficiency, particularly with respect to the image registration tools. CONCLUSIONS: The results of our observer study indicate that workstation technology is acceptable to radiation oncologists as an alternative to a view box for clinical detection of setup errors from digital portal images. Improvements in implementation, including more tools and a greater degree of automation in the image analysis tasks, are needed to make PortFolio more clinically practical.

Response of the canine esophagus to irradiation.

One hundred twenty-eight beagle dogs were randomized to receive thoracic irradiation with doses between 0 and 72 Gy in 1.5-Gy fractions over 6 weeks. Dogs were randomized to have either 33, 67 or 100% of their lung volume irradiated. The entire thoracic portion of the esophagus and variable portions of the fundus of the stomach were included in the treatment field at all volumes. Sixteen of the 128 dogs entered in the study developed clinical signs of esophagitis. These 16 dogs received doses between 45 and 72 Gy. Clinical signs of esophagitis/gastritis included dysphagia, anorexia, emesis, excessive salivation and weight loss that required force-feeding of a liquid diet. An ED50 of 67.2 Gy (95% CI 61.45-79.7 Gy) was calculated for the occurrence of clinical signs that required some supportive treatment. Three of the 16 dogs receiving 63 or 72 Gy failed to respond to treatment and were euthanized. Twenty-five other dogs were euthanized prior to 2 years due to other treatment-related complications. Two dogs died of causes not related to treatment. No late esophageal complications were observed in the remaining 98 dogs out to 2 years after irradiation. Esophageal specimens from 79 dogs were available for quantitative histological analysis 2 years after irradiation. Histological analysis showed a decrease in the percentage of glandular tissue with a corresponding increase in lamina propria and muscle.

Acceptability and usage patterns of an image analysis workstation.

Critical to the successful deployment and use of new computer systems is the acceptance of the system by the users, i.e., the clinicians. We describe a study which evaluated, in an experimental setting, the potential acceptability of an image analysis workstation for radiation therapy. The acceptability and usage patterns were measured using semi-structured questionnaires and maintaining logs of user interactions. The results of the study showed that the radiation oncologists, who were the subjects for the study, perceived the workstation as acceptable. The results also suggested several areas for improvement of workstation that could increase its acceptance in the clinical setting.

Benchmark test cases for evaluation of computer-based methods for detection of setup errors: realistic digitally reconstructed electronic portal images with known setup errors.

PURPOSE: The purpose of this investigation was to develop methods and software for computing realistic digitally reconstructed electronic portal images with known setup errors for use as benchmark test cases for evaluation and intercomparison of computer-based methods for image matching and detecting setup errors in electronic portal images. METHODS AND MATERIALS: An existing software tool for computing digitally reconstructed radiographs was modified to compute simulated megavoltage images. An interface was added to allow the user to specify which setup parameter(s) will contain computer-induced random and systematic errors in a reference beam created during virtual simulation. Other software features include options for adding random and structured noise, Gaussian blurring to simulate geometric unsharpness, histogram matching with a "typical" electronic portal image, specifying individual preferences for the appearance of the "gold standard" image, and specifying the number of images generated. The visible male computed tomography data set from the National Library of Medicine was used as the planning image. RESULTS: Digitally reconstructed electronic portal images with known setup errors have been generated and used to evaluate our methods for automatic image matching and error detection. Any number of different sets of test cases can be generated to investigate setup errors involving selected setup parameters and anatomic volumes. This approach has proved to be invaluable for determination of error detection sensitivity under ideal (rigid body) conditions and for guiding further development of image matching and error detection methods. Example images have been successfully exported for similar use at other sites. CONCLUSIONS: Because absolute truth is known, digitally reconstructed electronic portal images with known setup errors are well suited for evaluation of computer-aided image matching and error detection methods. High-quality planning images, such as the visible human CT scans from the National Library of Medicine, are essential for producing realistic images. Sets of test cases with systematic and random errors in selected setup parameters and anatomic volumes are suitable for use as standard benchmarks by the radiotherapy community. In addition to serving as an aid to research and development, benchmark images may also be useful for evaluation of commercial systems and as part of a quality assurance program for clinical systems. Test cases and software are available upon request.

Modulation transfer function for a large-area amorphous silicon image receptor.

The modulation transfer function (MTF) of an amorphous silicon (aSi) sensor array was measured using proper sampling techniques to determine the edge spread function (ESF). The detector under study was a 10 cm2 area detector (EG&G Heimann, RTM128) consisting of 128 x 128 aSi photodiodes arranged in a square array. Two independent methods for calculating the presampling MTF were implemented, based on finely sampling the ESF measurements produced using 40 kV x-rays from a Faxitron microfocal spot x-ray tube. The two calculations of the detector's presampling MTF are in excellent agreement, and are within 20% at the Nyquist frequency when compared with the ideal MTF based only on the size of the detector elements. ESF measurements were also made at 6 MV on a Siemens MD-2 linear accelerator. A calculation of the system presampling MTF was performed which included effects from the linear accelerator source, the lead block used to create the high contrast edge, and the aSi detector response.

Verifying radiotherapy treatment setup by interactive image registration.

Digital image analysis techniques can be used to assist the physician in diagnostic or therapeutic decision making. In radiation oncology, portal image registration can improve the accuracy of detection of errors during radiation treatment. Following a discussion of the general paradigm of interactive image registration, we describe PortFolio, a workstation for portal image analysis.

Core-based portal image registration for automatic radiotherapy treatment verification.

PURPOSE: Portal imaging is the most important quality assurance procedure for monitoring the reproducibility of setup geometry in radiation therapy. The role of portal imaging has become even more critical in recent years due to the migration of three-dimensional (3D) treatment planning technology, including high-precision conformal therapy, from the research setting to routine clinical practice. Unfortunately, traditional methods for acquiring and interpreting portal images suffer from a number of deficiencies that contribute to the well-documented observation that many setup errors go undetected, and some persist for a clinically significant portion of the prescribed dose. Significant improvements in both accuracy and efficiency of detecting setup errors can, in principle, be achieved by using automatic image registration for on-line screening of images obtained from electronic portal imaging devices (EPIDs). METHODS AND MATERIALS: This article presents recent developments in a method called core-based image analysis that shows great promise for achieving the desired improvements in error detection. Core-based image analysis is a fundamental computer vision method that is capable of exploiting the full power of EPIDs by providing for on-line detection of setup errors via automatic registration of user-selected anatomical structures. We describe a robust method for automatic portal image registration based on core analysis and demonstrate an approach for assessing both accuracy and precision of registration methods using realistic, digitally reconstructed portal radiographs (DRPRs) where truth is known. RESULTS: Automatic core-based analysis of a set of 20 DRPRs containing known, random field positioning errors was performed for a patient undergoing treatment for prostate cancer. In all cases, the reported translation was within 1 mm of the actual translation with mean absolute errors of 0.3 mm and standard deviations of 0.3 mm. In all cases, the reported rotation was within 0.6 degree of the actual rotation with a mean absolute error of 0.18 degree and a standard deviation of 0.23 degree. CONCLUSION: Our results, using digitally reconstructed portal radiographs that closely resemble clinical portal images, suggest that automatic core-based registration is suitable as an on-line screening tool for detecting and quantifying patient setup errors.

A portable software tool for computing digitally reconstructed radiographs.

PURPOSE: To develop a portable software tool for fast computation of digitally reconstructed radiographs (DRR) with a friendly user interface and versatile image format and display options. To provide a means for interfacing with commercial and custom three-dimensional (3D) treatment planning systems. To make the tool freely available to the Radiation Oncology community. METHODS AND MATERIALS: A computer program for computing DRRs was enhanced with new features and rewritten to increase computational efficiency. A graphical user interface was added to improve ease of data input and DRR display. Installer, programmer, and user manuals were written, and installation test data sets were developed. The code conforms to the specifications of the Cooperative Working Group (CWG) of the National Cancer Institute (NCI) Contract on Radiotherapy Treatment Planning Tools. RESULTS: The interface allows the user to select DRR input data and image formats primarily by point-and-click mouse operations. Digitally reconstructed radiograph formats are predefined by configuration files that specify 19 calculation parameters. Enhancements include improved contrast resolution for visualizing surgical clips, an extended source model to stimulate the penumbra region in a computed port film, and the ability to easily modify the CT numbers of objects contoured on the planning computed tomography (CT) scans. CONCLUSIONS: The DRR tool can be used with 3D planning systems that lack this functionality, or perhaps improve the quality and functionality of existing DRR software. The tool can be interfaced to 3D planning systems that run on most modern graphics workstations, and can also function as a stand-alone program.

A Monte Carlo study of accelerator head scatter.

The production of off-focus x rays in the head of a 6 MV linac has been investigated using the EGS4 Monte Carlo code. The purpose of the study was to identify the sources of off-focus radiation and the relative contribution for each source. Even though a particular energy and linac were modeled, the broad conclusions are expected to be general since the effects of head scatter are similar for most conventional head designs, regardless of manufacturer, energy, and model. The head components that were modeled include the exit window of the accelerating structure, target, beam stopper, flattening filter, monitor chamber, primary and secondary collimators, and air. Monoenergetic 6 MeV electrons were followed through the exit window, target, and beam stopper until all energy was expended. Primary- and higher-order x rays produced throughout the head were followed until they were either absorbed or passed through a plane at the isocenter. Sites of off-focus radiation were found to be diffusely distributed throughout the head, with the most intense sources being the primary collimator, flattening filter, and beam stopper. Data analysis shows that the collimator effect is determined primarily by the volume of the extended head-scatter source that is exposed to the point of measurement through the collimating system. The results of this study provide a rationale for developing extended source models to calculate the collimator factor for fields defined by arbitrary collimation. An additional advantage is an improvement in the agreement between measured and calculated isodose distributions.

The tetrad and hexad: maximum beam separation as a starting point for noncoplanar 3D treatment planning: prostate cancer as a test case.

PURPOSE: In contrast to computer optimized three-dimensional (3D) treatment planning, we have used maximally separated, noncoplanar beams as the starting point for 3D treatment planning of prostate cancer to maximize the rate of dose fall off from the target volume and minimize dose to surrounding tissues. MATERIALS AND METHODS: A planar four-field plan, a planar six-field plan, a tetrad plan, and a hexad plan are analyzed using a 3D treatment planning system which is capable of displaying real-time 3D dose distributions within volume reconstructed data sets (VISTAnet--an extension of the virtual simulator). The tetrad plan is based on the methane molecule and the hexad plan has a minimum separation of 58 degrees on beam entrance. All fields are conformal. The irradiated volume equals the clinical target volume plus a 1 cm margin. Competing plans are compared using cumulative dose-volume histograms and normal tissue complication probabilities. RESULTS: The crossover point, the isodose surface that conforms more to the beams than the target, is introduced and described. The hexad and tetrad plans result in tighter dose distributions when compared to the planar plans with the same number of beams. The tetrad plan treats a volume less than or equal to the planar six-field plan at isodose surfaces above 18% except between 37% and 44% where the tetrad volume is slightly larger. As expected from integral dose considerations, the amount of normal tissue receiving some radiation increases, but the amount receiving clinically significant amounts of radiation decreases as the number of beams increase. The plan involving the largest number of noncoplanar beams results in the tightest isodose distribution. Analysis of rectal and bladder cumulative dose volume histograms does not reveal a clearly superior plan based on normal tissue complication probabilities. CONCLUSIONS: Using basic principles of solid geometry, maximally separated beams without significant overlap on exit or entrance can be designed which minimize clinically significant dose to surrounding tissues and tighten the isodose distribution around the target volume. The emphasis of this treatment plan optimization is geometric in contrast to methods using computer optimization or artificial intelligence.

Digitally reconstructed fluoroscopy and other interactive volume visualizations in 3-D treatment planning.

PURPOSE: Add radiographic context to the beam's-eye-view used in 3-dimensional treatment planning. Improve methods for interactive visualization of anatomy and dose distributions. METHODS AND MATERIALS: Most 3-dimensional treatment planning systems feature a beam's-eye view that includes only graphical representations of patient anatomy. With input devices such as a mouse or trackball, the user interactively shapes the treatment field using the graphical models to provide geometric information. Radiographic context provides additional geometric information important for determining field shape. We have implemented digitally reconstructed fluoroscopy in the beam's-eye view by increasing the efficiency for computing digitally reconstructed radiographs. In addition we have improved algorithms for real-time surface and volume rendering for anatomy and doses using an experimental graphics supercomputer. RESULTS: Without radiographic context in the beam's-eye-view, field shapes were sometimes changed after simulation or portal images were obtained. Digitally reconstructed fluoroscopy has essentially eliminated these changes. Higher quality interactive three-dimensional displays improve the comprehension, confidence and efficiency of the user. Our improvements have already been implemented on one model of a new generation of commercial graphics workstations. CONCLUSION: Addition of radiographic context to the beam's-eye-view is recommended. Incorporation of higher quality interactive graphics is rapidly becoming practical and is encouraged.

VISTAnet: interactive real-time calculation and display of 3-dimensional radiation dose: an application of gigabit networking.

Three-dimensional treatment planning can allow the clinician to create plans that are highly individualized for each patient. However, in lifting the constraints traditionally imposed by 2-dimensional planning, the clinician is faced with the need to compare a much larger number of plans. Although methods to automate that process are being developed, it is not yet clear how well they will perform. VISTAnet is a 3 year collaborative effort between the Departments of Radiation Oncology and Computer Science at the University of North Carolina, the North Carolina Supercomputing Center, BellSouth, and GTE with the medical goal of providing real-time 3-dimensional radiation dose calculation and display. With VISTAnet technology and resources, the user can inspect 3-dimensional treatment plans in real-time along with the associated dose volume histograms and can fine tune these plans in real-time with regard to beam position, weighting, wedging, and shape. Thus VISTAnet provides an alternate and, possibly, complementary approach to computerized searches for optimal radiation treatment plans. Building this system has required the development of very fast radiation dose code, methods for simultaneously manipulating and modifying multiple radiation beams, and new visualizations of 3-dimensional dose distributions.

A finite-size pencil beam model for photon dose calculations in three dimensions.

A three-dimensional dose computation model employing a finite-size, diverging, pencil beam has been developed and is demonstrated for Cobalt-60 gamma rays. The square cross-section pencil beam is simulated in a semi-infinite water phantom by convolving the pencil beam photon fluence with the Monte Carlo point dose kernel for Cobalt-60. This finite-size pencil beam is calculated one time and becomes a new data base with which to build larger beams by two-dimensional superposition. The pencil beam fluence profile, angle correction for beam divergence, the Mayneord inverse square correction, radial and angular sampling rates, error propagation, and computation time have been investigated and are reported. Radial and angular sampling rates have a great effect on accuracy and their appropriate selection is important. Percent depth doses calculated by finite-size pencil beam superposition are within 1% of values calculated by full convolution and the agreement with values from the literature is within 6%. The latter disagreement is shown to be due to a low-energy photon component which is not modeled in other calculations. Computation time measurements show the pencil beam method to be faster than full convolution and one implementation of the differential-scatter-air-ratio (dSAR) method.

A comparison of postoperative techniques for carcinomas of the larynx and hypopharynx using 3-D dose distributions.

If a head and neck cancer originates low in the neck with a primary site below the shoulders, a technical challenge to the radiation oncologist exists in that the entire neck needs treatment while avoiding overlap of multiple fields on the spinal cord. No standard solution to this problem exists. We have developed a 3-D treatment planning tool that can be used to develop and compare 3-D treatment plans and dose distributions. Using this tool, we have studied the following techniques for the postoperative treatment of carcinomas of the larynx and hypopharynx, tumors that often embody the problems discussed above: (a) the mini-mantle technique used at the Massachussetts General Hospital, (b) a 3-field technique used at the University of Florida at Gainesville (UF 3-field), (c) a 3-field technique used at our institution and at many others (standard 3-field), and (d) the kicked out lateral technique used at our institution and at others. The 3-D dose distributions from these plans are compared. With 100% delivered just anterior to the vertebral body at mid-neck, the mini-mantle technique results in large 120% hot spots laterally and anteriorly in the neck. Near the mastoid tips, however, the dose falls to 100%. The upper neck nodes may be underdosed since this is 20% cooler than the lateral-anterior neck dose (where a large 120% hot spot exists). The spinal cord is adequately blocked. The two 3-field techniques result in small hot spots at the junction of the lateral and anterior fields. Because different methods are used to prevent overlap at the spinal cord, these hot spots occur anteriorly in the standard 3-field technique and laterally in the UF 3-field technique. The spinal cord block results in untreated neck tissue which can be supplemented with electrons in the standard 3-field technique, but is left untreated in the UF 3-field technique. Both techniques result in a generous length of spinal cord which does not receive full dose. The kicked out lateral technique treats the entire neck and reconstructed pharynx without matching fields at midneck. The upper mid mediastinum is underdosed 10-20% despite being within the posterior inferior portion of the beam. This could be minimized by using a tissue compensator. Unless there is significant subglottic extension or significant risk of disease in the upper mediastinum, we favor treating these malignancies with the kicked out lateral technique, which avoids the problem of junctioning lateral and anterior fields and provides a fairly homogeneous dose distribution.

The portable virtual simulator.

The Virtual Simulator is a software tool for support and management of the geometric component of 3-dimensional radiotherapy treatment design. The Virtual Simulator is a software implementation of a physical simulator with additional functionality not currently available on physical simulators. Treatment of a virtual patient, derived from CT or other source, is simulated using the Virtual Simulator in the same way a physical simulator would be used. The intent of this approach is to provide the user with a familiar working environment for radiotherapy treatment design. Key features include an effective and efficient user interface, and the use of computing techniques and software standards which enhance portability to a variety of computer workstations. The Virtual Simulator is implemented in the C programming language using the X Window System, and has been written with the generic UNIX workstation in mind. It has been demonstrated that it can be installed and run without modification on workstations from a number of vendors.

Virtual simulation: initial clinical results.

We have developed a graphics-based three-dimensional treatment design system that permits the physician to easily understand which anatomy will be treated for any arbitrary beam orientation. Our implementation of this system differs from others in that the software (the Virtual Simulator) simulates the full functionality of a (physical) radiation therapy simulator allowing it to be easily used by physicians. The details of the of our initial clinical experience with virtual simulation are presented in this paper. Virtual simulation was attempted in 71 patients and completed in 65. In 41/71 patients (58%), the beam orientations chosen differed significantly from those traditionally used in our department. Although virtual simulation lead to traditional radiation portals in the remaining patients, in 23/71 (32%) secondary blocking was designed which was different from that which would have been conventionally employed. Thus, overall, virtual simulation lead to treatment changes in 64/71 (90%) of the patients in whom it was attempted. In 78% of evaluable patients the treatment designed with virtual simulation could be implemented on the physical simulator with a precision of +/- 5 mm (+/- 3 mm for brain and head and neck). Thus virtual simulation allowed both accurate planning and execution of treatment plans that would be difficult to achieve with conventional methods.