D Khullar

Exploring feature-based approaches in PET images for predicting cancer treatment outcomes

Accumulating evidence suggests that characteristics of pre-treatment FDG-PET could be used as prognostic factors to predict outcomes in different cancer sites. Current risk analyses are limited to visual assessment or direct uptake value measurements. We are investigating intensity-volume histogram metrics and shape and texture features extracted from PET images to predict patients response to treatment. These approaches were demonstrated using datasets from cervix and head and neck cancers, where AUC of 0.76 and 1.0 were achieved, respectively. The preliminary results suggest that the proposed approaches could potentially provide better tools and discriminant power for utilizing functional imaging in clinical prognosis.

MicroRT - Small animal conformal irradiator

A novel small animal conformal radiation therapy system has been designed and prototyped: MicroRT. The microRT system integrates multimodality imaging, radiation treatment planning, and conformal radiation therapy that utilizes a clinical 192Ir isotope high dose rate source as the radiation source (teletherapy). A multiparameter dose calculation algorithm based on Monte Carlo dose distribution simulations is used to efficiently and accurately calculate doses for treatment planning purposes. A series of precisely machined tungsten collimators mounted onto a cylindrical collimator assembly is used to provide the radiation beam portals. The current design allows a source-to-target distance range of 1-8 cm at four beam angles: 0 degrees (beam oriented down), 90 degrees, 180 degrees, and 270 degrees. The animal is anesthetized and placed in an immobilization device with built-in fiducial markers and scanned using a computed tomography, magnetic resonance, or positron emission tomography scanner prior to irradiation. Treatment plans using up to four beam orientations are created utilizing a custom treatment planning system-microRTP. A three-axis computer-controlled stage that supports and accurately positions the animals is programmed to place the animal relative to the radiation beams according to the microRTP plan. The microRT system positioning accuracy was found to be submillimeter. The radiation source is guided through one of four catheter channels and placed in line with the tungsten collimators to deliver the conformal radiation treatment. The microRT hardware specifications, the accuracy of the treatment planning and positioning systems, and some typical procedures for radiobiological experiments that can be performed with the microRT device are presented.

Concurrent multimodality image segmentation by active contours for radiotherapy treatment planning

Multimodality imaging information is regularly used now in radiotherapy treatment planning for cancer patients. The authors are investigating methods to take advantage of all the imaging information available for joint target registration and segmentation, including multimodality images or multiple image sets from the same modality. In particular, the authors have developed variational methods based on multivalued level set deformable models for simultaneous 2D or 3D segmentation of multimodality images consisting of combinations of coregistered PET, CT, or MR data sets. The combined information is integrated to define the overall biophysical structure volume. The authors demonstrate the methods on three patient data sets, including a nonsmall cell lung cancer case with PET/CT, a cervix cancer case with PET/CT, and a prostate patient case with CT and MRI. CT, PET, and MR phantom data were also used for quantitative validation of the proposed multimodality segmentation approach. The corresponding Dice similarity coefficient (DSC) was 0.90±0.02(p<0.0001) with an estimated target volume error of 1.28±1.23% volume. Preliminary results indicate that concurrent multimodality segmentation methods can provide a feasible and accurate framework for combining imaging data from different modalities and are potentially useful tools for the delineation of biophysical structure volumes in radiotherapy treatment planning.

Deformable registration of abdominal kilovoltage treatment planning CT and tomotherapy daily megavoltage CT for treatment adaptation

In adaptive radiation therapy the treatment planning kilovoltage CT (kVCT) images need to be registered with daily CT images. Daily megavoltage CT (MVCT) images are generally noisier than the kVCT images. In addition, in the abdomen, low image contrast, differences in bladder filling, differences in bowel, and rectum filling degrade image usefulness and make deformable image registration very difficult. The authors have developed a procedure to overcome these difficulties for better deformable registration between the abdominal kVCT and MVCT images. The procedure includes multiple image preprocessing steps and a two deformable registration steps. The image preprocessing steps include MVCT noise reduction, bowel gas pockets detection and painting, contrast enhancement, and intensity manipulation for critical organs. The first registration step is carried out in the local region of the critical organs (bladder, prostate, and rectum). It requires structure contours of these critical organs on both kVCT and MVCT to obtain good registration accuracy on these critical organs. The second registration step uses the first step results and registers the entire image with less intensive computational requirement. The two-step approach improves the overall computation speed and works together with these image preprocessing steps to achieve better registration accuracy than a regular single step registration. The authors evaluated the procedure on multiple image datasets from prostate cancer patients and gynecological cancer patients. Compared to rigid alignment, the proposed method improves volume matching by over 60% for the critical organs and reduces the prostate landmark registration errors by 50%.

Feasibility of small animal cranial irradiation with the microRT system

PURPOSE To develop and validate methods for small-animal CNS radiotherapy using the microRT system. MATERIALS AND METHODS A custom head immobilizer was designed and built to integrate with a pre-existing microRT animal couch. The Delrin couch-immobilizer assembly, compatible with multiple imaging modalities (CT, microCT, microMR, microPET, microSPECT, optical), was first imaged via CT in order to verify the safety and reproducibility of the immobilization method. Once verified, the subject animals were CT-scanned while positioned within the couch-immobilizer assembly for treatment planning purposes. The resultant images were then imported into CERR, an in-house-developed research treatment planning system, and registered to the microRTP treatment planning space using rigid registration. The targeted brain was then contoured and conformal radiotherapy plans were constructed for two separate studies: (1) a whole-brain irradiation comprised of two lateral beams at the 90 degree and 270 degree microRT treatment positions and (2) a hemispheric (left-brain) irradiation comprised of a single A-P vertex beam at the 0 degree microRT treatment position. During treatment, subject animals (n=48) were positioned to the CERR-generated treatment coordinates using the three-axis microRT motor positioning system and were irradiated using a clinical Ir-192 high-dose-rate remote after-loading system. The radiation treatment course consisted of 5 Gy fractions, 3 days per week. 90% of the subjects received a total dose of 30 Gy and 10% received a dose of 60 Gy. RESULTS Image analysis verified the safety and reproducibility of the immobilizer. CT scans generated from repeated reloading and repositioning of the same subject animal in the couch-immobilizer assembly were fused to a baseline CT. The resultant analysis revealed a 0.09 mm average, center-of-mass translocation and negligible volumetric error in the contoured, murine brain. The experimental use of the head immobilizer added 0.1 mm to microRT spatial uncertainty along each axis. Overall, the total spatial uncertainty for the prescribed treatments was +/-0.3 mm in all three axes, a 0.2 mm functional improvement over the original version of microRT. Subject tolerance was good, with minimal observed side effects and a low procedure-induced mortality rate. Throughput was high, with average treatment times of 7.72 and 3.13 min/animal for the whole-brain and hemispheric plans, respectively (dependent on source strength). CONCLUSIONS The method described exhibits conformality more in line with the size differential between human and animal patients than provided by previous prevalent approaches. Using pretreatment imaging and microRT-specific treatment planning, our method can deliver an accurate, conformal dose distribution to the targeted murine brain (or a subregion of the brain) while minimizing excess dose to the surrounding tissue. Thus, preclinical animal studies assessing the radiotherapeutic response of both normal and malignant CNS tissue to complex dose distributions, which closer resemble human-type radiotherapy, are better enabled. The procedural and mechanistic framework for this method logically provides for future adaptation into other murine target organs or regions.

Dosimetric consequences of uncorrected setup errors in helical Tomotherapy treatments of breast-cancer patients

BACKGROUND AND PURPOSE The Tomotherapy Hi-Art II system allows acquisition of pre-treatment MVCT images to correct patient position. This work evaluates the dosimetric impact of uncorrected setup errors in breast-cancer radiation therapy. MATERIALS AND METHODS Breast-cancer patient-positioning errors were simulated by shifting the patient computed-tomography (CT) dataset relative to the planned photon fluence and re-computing the dose distributions. To properly evaluate the superficial region, film measurements were compared against the Tomotherapy treatment planning system (TPS) calculations. A simulation of the integrated dose distribution was performed to evaluate the setup error impact over the course of treatment. RESULTS Significant dose differences were observed for 11-mm shifts in the anterolateral and 3-mm shifts in the posteromedial directions. The results of film measurements in the superficial region showed that the TPS overestimated the dose by 14% at a 1-mm depth, improving to 3% at depths >or=5mm. Significant dose reductions in PTV were observed in the dose distributions simulated over the course of treatment. CONCLUSIONS Tomotherapys rotational delivery provides sufficient photon fluence extending beyond the skin surface to allow an up to 7-mm uncorrected setup error in the anterolateral direction. However, the steep dose falloff that conforms to the lung surface leads to compromised dose distributions with uncorrected posteromedial shifts. Therefore, daily image guidance and consequent patient repositioning is warranted for breast-cancer patients.

SU-FF-J-126: An Open-Source Radiotherapy Image Registration Toolkit Integrated with CERR

Purpose: We developed an image registration module for the open‐source system CERR (the computational environment for radiotherapy research) for the purpose of radiation therapyimage guidance quality assurance and image analysis. This new module provides functionality useful for registration algorithm optimization, visualization, analysis, and validation. Method and Materials: We implemented a series of automatic (rigid and deformable) and semi‐automatic image registration methods. We implemented 20+ original and variant deformable methods, including optical flow based methods with different constraints, level set motion based methods and demon based methods. We imported ITK rigid image registration methods into CERR, including affine transform, similarity transform, Euler3D transform, versor3D transform, etc. We also implemented a multi‐grid framework to improve the speed and accuracy of the automatic registration process. In addition, we implemented 3D control point matching methods. We use several similarity metrics, including MSE, cross correlation, MI etc., to quantitatively analyze and validate the registration results. For results visualization, we implemented functions such as difference, dynamic checkerboard, image mirror, deformation field vector and grid plotting, etc. We programmed the GUI in MATLAB and Java, deformable methods in MATLAB and ITK rigid registration methods in C++. Results: The new CERR module supports 3D rigid and deformable registration. By monitoring the registration process and measuring the results, we can optimize the registration methods by tuning the parameters. We tested the deformable methods with chest CT images and the results were satisfied. Conclusion: The goal of this work is to extend the functions of CERR, to provide an open source implementation of image registration algorithms for radiotherapy research. As an ongoing project, we plan to provide more registration methods and further improve the integration of the registration results with treatment planning data.

SU‐EE‐A1‐06: Helical Tomotherapy Planning for Left‐Sided Breast Cancer Patients with Positive Lymph Nodes: Compared to Conventional Multi‐Port‐Breast Technique

Purpose: The objective of this study was to evaluate the feasibility of using helical tomotherapy for left‐sided breast cancer patients with involved lymph nodes. Method and Materials: Four left‐sided breast cancer patients treated using conventional multi‐port‐breast technique were retrospectively planned on Tomotherapy planning system. PTVs including chest‐wall/breast, supraclavicular, axillary and internal‐ mammary lymphnodes were contoured. Optimized treatment plans were generated on Tomotherapy TPS using 25mm field‐width with pitch of 0.42. The modulation factors varied from 1.5–2.6. All plans had a prescription of 50.4Gy to 93% and 46.9Gy to 98% of the PTV. Directional blocking was used on the right side to limit the dose to the contra‐lateral‐breast and lung. The optimization goals for planning were to protect the heart and lungs from receiving excessive doses. Resulting plans were compared against a conventional multi‐port breast technique. Lung toxicities using the Lymann‐Kutcher‐Burman model were estimated for tomotherapy plans. The parameters used for these calculations are TD50%=30.8Gy, slope(m)=0.37 and the exponent(a)=1. Results: Tomotherapy increased the minimum dose to the PTV (D99% = 44.6Gy for tomotherapy versus 30.5Gy for 3D) while improving the homogeneity index (HI = 1.16 for tomotherapy and 1.52 for 3D). The mean V20Gy for the left lung decreased from 32.6% (3D) to 16.4% (tomotherapy) while keeping the mean right lung dose well under 4Gy. However, the mean V5Gy volume increased from 26.4% (3D) to 42.6% (tomotherapy). The mean V35Gy for the heart decreased from 6.5%–2.5%, while the mean heart dose increased from 9.5Gy–11.3Gy for conventional and tomotherapy, respectively. The estimated NTCP for lung range from 1.4% to 2.4% for tomotherapy plans. Conclusion: Tomotherapy plans have better conformity and dose homogeneity than the 3D‐ plans. Tomotherapy provided improved sparing for the heart and lungs.Conflict of Interest: This work supported in part by Tomotherapy, Inc.

TH-C-224C-02: MicroRT/microRTP: A Conformal Small Animal Planning and Irradiation System

Purpose: We have developed a novel small animal radiation therapy device (microRT), which integrates multi‐modality imaging,radiation treatment planning, and conformal radiation therapy. In this study, we evaluated the accuracy of the treatment planning and positioning systems of the microRT device. Method and Materials: The microRT system utilizes a clinical 192Ir HDR source collimated via machined tungsten inserts to deliver photon beams at a source to target distances of 1–8cm at four angles (0, 90, 180, and 270). Beams were modeled using Monte Carlo and a parameterized analytic dose engine was created. Radiochromic film (5mm steps) in a solid water phantom was used to evaluate actual delivered doses in multiple planes. Treatment plans using these beams were created by a custom treatment planning system (microRTP) based on imported fiducial‐registered imaging (CT, MR, PET) of animals immobilized in the treatment position. A three‐axis computer‐controlled stage supports and positions animals in the beams according to the microRTP plan. Validation of the positioning system was performed using a phantom and images of phantom and collimator via a kV C‐arm. Results: The analytic dosemodel agreed with the Monte‐Carlo predicted dose within 5% and 10% outside and inside the 1 mm deep build‐up regions, respectively. Film dosimetry agreed with the analytic model within 10% and also demonstrated an effective field diameter of 8mm at 17mm from the source. The 192Ir line source geometry caused a radial anisotropy of up to 12% at 17 mm depth from the source. The positioning accuracy of the animal support hardware was sub‐millimeter. Conclusions: The microRT system provides conformal radiation therapy based on pre‐treatment imaging and planning for small animal models of cancer and tissue injury. This work supported in part by NIH R21 CA108677 and by a grant from Varian, Inc.

TH‐D‐BRD‐01: New Developments in The Computational Environment for Radiotherapy Research (CERR) Software System

Purpose: CERR continues to be used across the world for radiotherapy research, and was downloaded over 1,000 times in the last year. We present recent improvements and changes to the system in response to user requests and research needs. Methods: New developments in the last year include: (1) integration of more powerful image registration tools (a multi‐scale demons algorithm), (2) the development of an extensive plan robustness analysis module (used to statistically simulate the effect of random, systematic, and contouring variations over a course of treatment), (3) generalizations to the java‐based DICOM input and output, (4) documentation now available via an extensive wiki page, and (5) a new tool that indicates the location of cold spots in a target volume by plotting the distance to the edge of a target volume for each voxel below a user‐selected dose threshold. Results: The image registration module has been stabilized and is being used extensively. The plan robustness module provides the statistical effect on DVH curves of presumed uncertainties. These ‘dose‐distance histograms’ give the user a simple graphical method for understanding the location of cold spots in target volumes. Documentation is now much more extensive. Conclusion: The updates to CERR will enhance user experience in using image registration and plan QA to validate treatment plan. Partially supported by NIH grants R01 CA11820 and R01 CA85181.