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  • Dose Distribution Prediction in Isodose Feature-Preserving Voxelization Domain Using Deep Convolutional Neural Network. Medical physics Ma, M., Buyyounouski, M. K., Vasudevan, V., Xing, L., Yang, Y. 2019

    Abstract

    PURPOSE: To implement a framework for dose prediction using a deep convolutional neural network (CNN) based on the concept of isodose feature-preserving voxelization (IFPV) in simplifying the representation of the dose distribution.METHODS: The concept of IFPV was introduced for concise representation of a treatment plan. IFPV is a sparse voxelization scheme that partitions the voxels into subgroups according to their geometric, anatomical and dosimetric features. In this study a deep CNN was constructed to build up a dose prediction model in IFPV domain based on 60 volumetric modulated arc therapy (VMAT) treatment plans from a database of previously treated 70 prostate cancer patients. The dose prediction model learns the contour to dose relationship and predicts the dose distribution in IFPV domain given the input contours. Additional 10 independent prostate cases were selected as testing data. DVH comparison, dose difference maps and residual analysis with the sum of absolute residual (SAR) were used to evaluate the performance of the proposed method.RESULTS: The proposed IFPV-based method achieved good prediction performance in terms of DVH comparison and dose difference maps. Statistical results of SARs showed that the IFPV-based method is comparable with voxel-based method even though the number of dose representation points used in the IFPV-based method was substantially reduced. The proposed approach achieved mean SARs of 0.029 0.020 and 0.077 0.030 for bladder and rectum, respectively, compared with mean SARs of 0.0390.029 and 0.0690.028 in the conventional voxel-based method.CONCLUSIONS: A novel deep CNN-based dose prediction method in IFPV domain was proposed. The proposed approach has great potential to significantly improve the efficiency of dose prediction and facilitate the treatment planning workflow. This article is protected by copyright. All rights reserved.

    View details for DOI 10.1002/mp.13618

    View details for PubMedID 31112305

  • Incorporating dosimetric features into the prediction of 3D VMAT dose distributions using deep convolutional neural network. Physics in medicine and biology Ma, M., Kovalchuk, N., Buyyounouski, M. K., Xing, L., Yang, Y. 2019

    Abstract

    An accurate prediction of achievable dose distribution on a patient specific basis would greatly improve IMRT/VMAT planning in both efficiency and quality. Recently machine learning techniques have been proposed for IMRT dose prediction based on patient's contour information from planning CT. In these existing prediction models geometric/anatomic features were learned for building the dose prediction models and few features that characterize the dosimetric properties of the patients were utilized. In this study we propose a method to incorporate the dosimetric features in the construction of a more reliable dose prediction model based on the deep convolutional neural network (CNN). In addition to the contour information, the dose distribution from a PTV-only plan (i.e., the plan with the best PTV coverage by sacrificing the OARs sparing) is also employed as the model input to build a deep learning based dose prediction model. A database of 60 volumetric modulated arc therapy (VMAT) plans for the prostate cancer patients was used for training. The trained prediction model was then tested on a cohort of 10 cases. Dose difference maps, DVHs, dosimetric endpoints and statistical analysis of the sum of absolute residuals (SARs) were used to evaluate the proposed method. Our results showed that the mean SARs for the PTV, bladder and rectum using our method were 0.0070.003, 0.0350.032 and 0.0670.037 respectively, lower than the SARs obtained with the contours-based method, indicating the potential of the proposed approach in accurately predicting dose distribution.

    View details for PubMedID 31082805

  • Markerless pancreatic tumor target localization enabled by deep learning. International journal of radiation oncology, biology, physics Zhao, W., Shen, L., Han, B., Yang, Y., Cheng, K., Toesca, D. A., Koong, A. C., Chang, D. T., Xing, L. 2019

    Abstract

    To estimate the impact of radiotherapy (RT) on non-breast second malignant neoplasms (SMNs) in young women survivors of stage I-IIIA breast cancer.Women aged 20-44 years diagnosed with stage I-IIIA breast cancer (1988-2008) were identified in Surveillance, Epidemiology, and End Results (SEER) 9 registries. Bootstrapping approach and competing risk proportional hazards models were used to evaluate the effect of RT on non-breast SMN risk. The analysis was repeated in racial subgroups. Radio-tolerance score (RTS) analysis of normal airway epithelium was performed using Gene Expression Omnibus (GEO) datasets.Within records of 30,003 women with primary breast cancer, 20,516 eligible patients were identified (including 2,183 African Americans [AAs] and 16,009 Caucasians). The 25-year cumulative incidences of SMN were 5.2% and 3.6% (RT vs. no-RT) for AAs with 12.8-year and 17.4-year (RT vs. no-RT) median follow-up (HR=1.81, 95% bootstrapping confidence intervals [BCIs] [1.02, 2.50], P < 0.05); and 6.4% and 5.9% (RT vs. no-RT) for Caucasians with 14.3-year and 18.1-year (RT vs. no-RT) median follow-up (HR=1.10, 95% BCI [0.61, 1.40], P > 0.05). The largest portion of excess RT-related SMN risk was lung cancer (AA: HR=2.08, 95% BCI [1.02, 5.39], P < 0.05; Caucasian: HR=1.50, 95% BCI [0.84, 5.38], P > 0.05). STEPP analysis revealed higher post-RT non-breast SMN risk essentially throughout entire age range 20-44 years, with larger HR for RT in AAs. RTS of normal airway epithelium from young AA women was significantly lower than that from young Caucasian women (P = 0.038).With a projected 25-year follow-up, RT is associated with elevated risk of non-breast SMNs, particularly second lung cancer, in young women survivors of stage I-IIIA breast cancer, especially higher in AA women than Caucasian women.

    View details for DOI 10.1016/j.ijrobp.2019.05.071

    View details for PubMedID 31201892

  • Dosimetric Features-Driven Machine Learning Model for DVHs Prediction in VMAT Treatment Planning. Medical physics Ma, M., Kovalchuk, N., Buyyounouski, M. K., Xing, L., Yang, Y. 2018

    Abstract

    PURPOSE: Few features characterizing the dosimetric properties of the patients are included in currently available dose-volume histogram (DVH) prediction models, making it intractable to build a correlative relationship between the input and output parameters. Here we use PTV-only treatment plans of the patients (i.e., the achievable dose distribution in the absence of organs-at-risks (OARs) constraints) to estimate the potentially achievable quality of treatment plans and establish a machine learning-based DVH prediction framework with the use of the dosimetric metric as model input parameters.METHODS: A support vector regression (SVR) approach was used as the backbone of our machine learning model. A database containing volumetric modulated arc therapy (VMAT) plans of 63 prostate cancer patients were used. For each patient, the PTV-only plan was generated first. A correlative relationship between the OAR DVH of the PTV-only plan (model input) and the corresponding DVH of the clinical treatment plan (CTP) (model output) was then established with the 53 training cases. The prediction model was tested by the validation cohort of 10 cases.RESULTS: For the training cohort, the checks of dosimetric endpoints (DEs) indicated that 52 out of 53 plans (98%) were within 10% error bound for bladder, and 45 out of 53 plans (85%) were within 10% error bound for rectum. In the validation tests, 92% and 96% of the DEs were within the 10% error bounds for bladder and rectum respectively, and 8 out of 10 validation plans (80%) were within 10% error bound for both bladder and rectum. The sum of absolute residuals (SAR) achieved mean 0.034 0.028 and 0.046 0.021 for the bladder and rectum, respectively.CONCLUSIONS: A novel dosimetric features-driven machine learning model with the use of PTV-only plan has been established for DVH prediction. The framework is capable of efficiently generating best achievable DVHs for VMAT planning. This article is protected by copyright. All rights reserved.

    View details for PubMedID 30536442

  • Cumulative dose of radiation therapy of hepatocellular carcinoma patients and its deterministic relation to radiation-induced liver disease MEDICAL DOSIMETRY Huang, P., Yu, G., Kapp, D. S., Bian, X., Ma, C., Li, H., Chen, J., Liang, Y., Zhang, Y., Qin, S., Xie, Y., Yang, Y., Yin, Y., Xing, L., Li, D. 2018; 43 (3): 258?66

    Abstract

    This study aimed to investigate the relationship between dose and radiation-induced liver disease (RILD) in patients with hepatocellular carcinoma (HCC) receiving 3-dimensional conformal radiotherapy (3DCRT). Twenty-three patients with HCC who received conventional fractionated 3DCRT, including 7 who were diagnosed with classic RILD, were enrolled in this retrospective investigation. Cone-beam computed tomography (CBCT) scans were acquired at the time of treatment for each patient. The beams from each patient's treatment plan were applied to each pretreatment CBCT (the modified CBCT or mCBCT) to construct the delivered dose distribution of the day considering inter-treatment anatomy changes. The daily doses were summed together with the help of deformable image registration (DIR) to obtain the adjusted cumulative dose (Dadjusted). The dose changes to the normal liver between the original planned dose (Dplan) and Dadjusted were evaluated by V20, V30, V40, and the mean dose to normal liver (MDTNL). Univariate analysis was performed to identify the significant dose changes. Among the 23 patients, the liver V20, V30, V40, and MDTNL showed significant differences between Dplan and Dadjusted, with average values of these parameters increased by 4.1%, 4.7%, 4.5%, and 3.9?Gy, respectively (p?

    View details for PubMedID 29198389

  • Feasibility of optimizing intensity-modulated radiation therapy plans based on measured mucosal dose adjacent to dental fillings and toxicity outcomes JOURNAL OF APPLIED CLINICAL MEDICAL PHYSICS Seol, S., Aggarwal, S., von Eyben, R., Wang, Z., Chan, C., Say, C., Xing, L., Hara, W., Yang, Y., Quynh Thu Le 2018; 19 (5): 444?52

    Abstract

    We prospectively investigated the feasibility of IMRT treatment plan optimization based on dosimeter measurements of lateral tongue mucosal dose adjacent to the dental fillings and evaluated dose-toxicity relationship and factors affecting oral mucositis (OM) in head and neck cancer patients. Twenty-nine head and neck cancer patients with metallic dental fillings who were scheduled to undergo fractionated external beam radiation therapy (RT) chemotherapy were enrolled. The lateral tongue dose was measured and if the calculated dose for the entire treatment was ?35 Gy, a re-plan was generated to reduce the lateral tongue mucosal dose. OM was graded weekly according to Common Terminology Criteria for Adverse Events version 4.0 and the patients completed the Oral Mucositis Weekly Questionnaire-Head and Neck Cancer. The result showed that it was not feasible to optimize the IMRT plan based on measured tongue dose in most of the patients who needed re-plan as re-planning compromised the target coverage in 60% of these patients. The duration of grade (Gr) 2 OM was correlated with measured lateral tongue dose (P = 0.050). Concurrent cetuximab was significantly associated with faster onset of Gr2 OM than concurrent cisplatin (P = 0.006) and with longer duration of OM (P = 0.041) compared to concurrent cisplatin or IMRT-alone. The pattern of reported pain over time was significantly different for each treatment type (RT and cetuximab, RT and cisplatin and RT-alone) and depending on the dose level (P = 0.006). In conclusion, optimizing the IMRT plan based on measured lateral tongue dose was not feasible. Measured lateral tongue dose was significantly correlated with longer duration of OM ?Gr2, and concurrent cetuximab was associated with earlier onset and longer duration of OM ?Gr2.

    View details for PubMedID 29984915

  • A unified material decomposition framework for quantitative dual- and triple-energy CT imaging. Medical physics Zhao, W., Vernekohl, D., Han, F., Han, B., Peng, H., Yang, Y., Xing, L., Min, J. K. 2018

    Abstract

    PURPOSE: Many clinical applications depend critically on the accurate differentiation and classification of different types of materials in patient anatomy. This work introduces a unified framework for accurate nonlinear material decomposition and applies it, for the first time, in the concept of triple-energy CT (TECT) for enhanced material differentiation and classification as well as dual-energy CT (DECT).METHODS: We express polychromatic projection into a linear combination of line integrals of material-selective images. The material decomposition is then turned into a problem of minimizing the least-squares difference between measured and estimated CT projections. The optimization problem is solved iteratively by updating the line integrals. The proposed technique is evaluated by using several numerical phantom measurements under different scanning protocols. The triple-energy data acquisition is implemented at the scales of micro-CT and clinical CT imaging with commercial "TwinBeam" dual-source DECT configuration and a fast kV switching DECT configuration. Material decomposition and quantitative comparison with a photon counting detector and with the presence of a bow-tie filter are also performed.RESULTS: The proposed method provides quantitative material- and energy-selective images examining realistic configurations for both DECT and TECT measurements. Compared to the polychromatic kV CT images, virtual monochromatic images show superior image quality. For the mouse phantom, quantitative measurements show that the differences between gadodiamide and iodine concentrations obtained using TECT and idealized photon counting CT (PCCT) are smaller than 8 and 1mg/mL, respectively. TECT outperforms DECT for multicontrast CT imaging and is robust with respect to spectrum estimation. For the thorax phantom, the differences between the concentrations of the contrast map and the corresponding true reference values are smaller than 7mg/mL for all of the realistic configurations.CONCLUSIONS: A unified framework for both DECT and TECT imaging has been established for the accurate extraction of material compositions using currently available commercial DECT configurations. The novel technique is promising to provide an urgently needed solution for several CT-based diagnostic and therapy applications, especially for the diagnosis of cardiovascular and abdominal diseases where multicontrast imaging is involved.

    View details for PubMedID 29679500

  • 4D VMAT planning and verification technique for dynamic tracking using a direct aperture deformation (DAD) method JOURNAL OF APPLIED CLINICAL MEDICAL PHYSICS Zhang, Y., Yang, Y., Fu, W., Li, X., Li, T., Heron, D. E., Huq, M. S. 2017; 18 (2): 50-61

    Abstract

    We developed a four-dimensional volumetric modulated arc therapy (4D VMAT) planning technique for moving targets using a direct aperture deformation (DAD) method and investigated its feasibility for clinical use. A 3D VMAT plan was generated on a reference phase of a 4D CT dataset. The plan was composed of a set of control points including the beam angle, MLC apertures and weights. To generate the 4D VMAT plan, these control points were assigned to the closest respiratory phases using the temporal information of the gantry angle and respiratory curve. Then, a DAD algorithm was used to deform the beam apertures at each control point to the corresponding phase to compensate for the tumor motion and shape changes. Plans for a phantom and five lung cases were included in this study to evaluate the proposed technique. Dosimetric comparisons were performed between 4D and 3D VMAT plans. Plan verification was implemented by delivering the 4D VMAT plans on a moving QUASAR? phantom driven with patient-specific respiratory curves. The phantom study showed that the 4D VMAT plan generated with the DAD method was comparable to the ideal 3D VMAT plan. DVH comparisons indicated that the planning target volume (PTV) coverages and minimum doses were nearly invariant, and no significant difference in lung dosimetry was observed. Patient studies revealed that the GTV coverage was nearly the same; although the PTV coverage dropped from 98.8% to 94.7%, and the mean dose decreased from 64.3 to 63.8 Gy on average. For the verification measurements, the average gamma index pass rate was 98.6% and 96.5% for phantom 3D and 4D VMAT plans with 3%/3 mm criteria. For patient plans, the average gamma pass rate was 96.5% (range 94.5-98.5%) and 95.2% (range 94.1-96.1%) for 3D and 4D VMAT plans. The proposed 4D VMAT planning technique using the DAD method is feasible to incorporate the intra-fraction organ motion and shape change into a 4D VMAT planning. It has great potential to provide high plan quality and delivery efficiency for moving targets.

    View details for DOI 10.1002/acm2.12053

    View details for Web of Science ID 000397498300008

    View details for PubMedID 28300367

  • Automating quality assurance of digital linear accelerators using a radioluminescent phosphor coated phantom and optical imaging. Physics in medicine and biology Jenkins, C. H., Naczynski, D. J., Yu, S. S., Yang, Y., Xing, L. 2016; 61 (17): L29-37

    Abstract

    Performing mechanical and geometric quality assurance (QA) tests for medical linear accelerators (LINAC) is a predominantly manual process that consumes significant time and resources. In order to alleviate this burden this study proposes a novel strategy to automate the process of performing these tests. The autonomous QA system consists of three parts: (1) a customized phantom coated with radioluminescent material; (2) an optical imaging system capable of visualizing the incidence of the radiation beam, light field or lasers on the phantom; and (3) software to process the captured signals. The radioluminescent phantom, which enables visualization of the radiation beam on the same surface as the light field and lasers, is placed on the couch and imaged while a predefined treatment plan is delivered from the LINAC. The captured images are then processed to self-calibrate the system and perform measurements for evaluating light field/radiation coincidence, jaw position indicators, cross-hair centering, treatment couch position indicators and localizing laser alignment. System accuracy is probed by intentionally introducing errors and by comparing with current clinical methods. The accuracy of self-calibration is evaluated by examining measurement repeatability under fixed and variable phantom setups. The integrated system was able to automatically collect, analyze and report the results for the mechanical alignment tests specified by TG-142. The average difference between introduced and measured errors was 0.13 mm. The system was shown to be consistent with current techniques. Measurement variability increased slightly from 0.1 mm to 0.2 mm when the phantom setup was varied, but no significant difference in the mean measurement value was detected. Total measurement time was less than 10 minutes for all tests as a result of automation. The system's unique features of a phosphor-coated phantom and fully automated, operator independent self-calibration offer the potential to streamline the QA process for modern LINACs.

    View details for DOI 10.1088/0031-9155/61/17/L29

    View details for PubMedID 27514654

  • Evaluation of on-board kV cone beam CT (CBCT)-based dose calculation PHYSICS IN MEDICINE AND BIOLOGY Yang, Y., Schreibmann, E., Li, T., Wang, C., Xing, L. 2007; 52 (3): 685-705

    Abstract

    On-board CBCT images are used to generate patient geometric models to assist patient setup. The image data can also, potentially, be used for dose reconstruction in combination with the fluence maps from treatment plan. Here we evaluate the achievable accuracy in using a kV CBCT for dose calculation. Relative electron density as a function of HU was obtained for both planning CT (pCT) and CBCT using a Catphan-600 calibration phantom. The CBCT calibration stability was monitored weekly for 8 consecutive weeks. A clinical treatment planning system was employed for pCT- and CBCT-based dose calculations and subsequent comparisons. Phantom and patient studies were carried out. In the former study, both Catphan-600 and pelvic phantoms were employed to evaluate the dosimetric performance of the full-fan and half-fan scanning modes. To evaluate the dosimetric influence of motion artefacts commonly seen in CBCT images, the Catphan-600 phantom was scanned with and without cyclic motion using the pCT and CBCT scanners. The doses computed based on the four sets of CT images (pCT and CBCT with/without motion) were compared quantitatively. The patient studies included a lung case and three prostate cases. The lung case was employed to further assess the adverse effect of intra-scan organ motion. Unlike the phantom study, the pCT of a patient is generally acquired at the time of simulation and the anatomy may be different from that of CBCT acquired at the time of treatment delivery because of organ deformation. To tackle the problem, we introduced a set of modified CBCT images (mCBCT) for each patient, which possesses the geometric information of the CBCT but the electronic density distribution mapped from the pCT with the help of a BSpline deformable image registration software. In the patient study, the dose computed with the mCBCT was used as a surrogate of the 'ground truth'. We found that the CBCT electron density calibration curve differs moderately from that of pCT. No significant fluctuation was observed in the calibration over the period of 8 weeks. For the static phantom, the doses computed based on pCT and CBCT agreed to within 1%. A notable difference in CBCT- and pCT-based dose distributions was found for the motion phantom due to the motion artefacts which appeared in the CBCT images (the maximum discrepancy was found to be approximately 3.0% in the high dose region). The motion artefacts-induced dosimetric inaccuracy was also observed in the lung patient study. For the prostate cases, the mCBCT- and CBCT-based dose calculations yielded very close results (<2%). Coupled with the phantom data, it is concluded that the CBCT can be employed directly for dose calculation for a disease site such as the prostate, where there is little motion artefact. In the prostate case study, we also noted a large discrepancy between the original treatment plan and the CBCT (or mCBCT)-based calculation, suggesting the importance of inter-fractional organ movement and the need for adaptive therapy to compensate for the anatomical changes in the future.

    View details for DOI 10.1088/0031-9155/52/3/011

    View details for Web of Science ID 000243684600011

    View details for PubMedID 17228114

  • Four-dimensional cone-beam computed tomography using an on-board imager MEDICAL PHYSICS Li, T., Xing, L., Munro, P., McGuinness, C., Chao, M., Yang, Y., Loo, B., Koong, A. 2006; 33 (10): 3825-3833

    Abstract

    On-board cone-beam computed tomography (CBCT) has recently become available to provide volumetric information of a patient in the treatment position, and holds promises for improved target localization and irradiation dose verification. The design of currently available on-board CBCT, however, is far from optimal. Its quality is adversely influenced by many factors, such as scatter, beam hardening, and intra-scanning organ motion. In this work we quantitatively study the influence of organ motion on CBCT imaging and investigate a strategy to acquire high quality phase-resolved [four-dimensional (4D)] CBCT images based on phase binning of the CBCT projection data. An efficient and robust method for binning CBCT data according to the patient's respiratory phase derived in the projection space was developed. The phase-binned projections were reconstructed using the conventional Feldkamp algorithm to yield 4D CBCT images. Both phantom and patient studies were carried out to validate the technique and to optimize the 4D CBCT data acquisition protocol. Several factors that are important to the clinical implementation of the technique, such as the image quality, scanning time, number of projections, and radiation dose, were analyzed for various scanning schemes. The general references drawn from this study are: (i) reliable phase binning of CBCT projections is accomplishable with the aid of external or internal marker and simple analysis of its trace in the projection space, and (ii) artifact-free 4D CBCT images can be obtained without increasing the patient radiation dose as compared to the current 3D CBCT scan.

    View details for DOI 10.1118/1.2349692

    View details for Web of Science ID 000241424100024

    View details for PubMedID 17089847

  • Overview of image-guided radiation therapy MEDICAL DOSIMETRY Xing, L., Thorndyke, B., Schreibmann, E., Yang, Y., Li, T., Kim, G., Luxton, G., Koong, A. 2006; 31 (2): 91-112

    Abstract

    Radiation therapy has gone through a series of revolutions in the last few decades and it is now possible to produce highly conformal radiation dose distribution by using techniques such as intensity-modulated radiation therapy (IMRT). The improved dose conformity and steep dose gradients have necessitated enhanced patient localization and beam targeting techniques for radiotherapy treatments. Components affecting the reproducibility of target position during and between subsequent fractions of radiation therapy include the displacement of internal organs between fractions and internal organ motion within a fraction. Image-guided radiation therapy (IGRT) uses advanced imaging technology to better define the tumor target and is the key to reducing and ultimately eliminating the uncertainties. The purpose of this article is to summarize recent advancements in IGRT and discussed various practical issues related to the implementation of the new imaging techniques available to radiation oncology community. We introduce various new IGRT concepts and approaches, and hope to provide the reader with a comprehensive understanding of the emerging clinical IGRT technologies. Some important research topics will also be addressed.

    View details for DOI 10.1016/j.meddos.2005.12.004

    View details for Web of Science ID 000237818000002

    View details for PubMedID 16690451

  • Model-based image reconstruction for four-dimensional PET MEDICAL PHYSICS Li, T., Thorndyke, B., Schreibmann, E., Yang, Y., Xing, L. 2006; 33 (5): 1288-1298

    Abstract

    Positron emission tonography (PET) is useful in diagnosis and radiation treatment planning for a variety of cancers. For patients with cancers in thoracic or upper abdominal region, the respiratory motion produces large distortions in the tumor shape and size, affecting the accuracy in both diagnosis and treatment. Four-dimensional (4D) (gated) PET aims to reduce the motion artifacts and to provide accurate measurement of the tumor volume and the tracer concentration. A major issue in 4D PET is the lack of statistics. Since the collected photons are divided into several frames in the 4D PET scan, the quality of each reconstructed frame degrades as the number of frames increases. The increased noise in each frame heavily degrades the quantitative accuracy of the PET imaging. In this work, we propose a method to enhance the performance of 4D PET by developing a new technique of 4D PET reconstruction with incorporation of an organ motion model derived from 4D-CT images. The method is based on the well-known maximum-likelihood expectation-maximization (ML-EM) algorithm. During the processes of forward- and backward-projection in the ML-EM iterations, all projection data acquired at different phases are combined together to update the emission map with the aid of deformable model, the statistics is therefore greatly improved. The proposed algorithm was first evaluated with computer simulations using a mathematical dynamic phantom. Experiment with a moving physical phantom was then carried out to demonstrate the accuracy of the proposed method and the increase of signal-to-noise ratio over three-dimensional PET. Finally, the 4D PET reconstruction was applied to a patient case.

    View details for DOI 10.1118/1.2192581

    View details for Web of Science ID 000237673600012

    View details for PubMedID 16752564

  • Optimization of radiotherapy dose-time fractionation with consideration of tumor specific biology MEDICAL PHYSICS Yang, Y., Xing, L. 2005; 32 (12): 3666-3677

    Abstract

    The "four Rs" of radiobiology play an important role in the design of radiation therapy treatment protocol. The purpose of this work is to explore their influence on external beam radiotherapy for fast and slowly proliferating tumors and develop an optimization framework for tumor-biology specific dose-time-fractionation scheme. The linear quadratic model is used to describe radiation response of tumor, in which the time dependence of sublethal damage repair and the redistribution and reoxygenation effects are included. The optimum radiotherapeutic strategy is defined as the treatment scheme that maximizes tumor biologically effective dose (BED) while keeping normal tissue BED constant. The influence of different model parameters on total dose, overall treatment time, fraction size, and intervals is also studied. The results showed that, for fast proliferating tumors, the optimum overall time is similar to the assumed kickoff time T(k) and almost independent of interval patterns. Significant increase in tumor control can be achieved using accelerated schemes for the tumors with doubling time smaller than 3 days, but little is gained for those with doubling time greater than 5 days. The incomplete repair of normal tissues between two consecutive fractions in standard fractionation has almost no influence on the fractional doses, even for the hyperfractionation with an interval time of 8 h. However, when the resensitization effect is included, the fractional doses at the beginning and end of each irradiated week become obviously higher than others in the optimum scheme and the hyperfractionation scheme has little advantage over the standard or hypofractionation one. For slowly proliferating tumors, provided that the alpha/beta ratio of the tumor is comparable to that of the normal tissues, a hypofractionation is more favorable. The overall treatment time should be larger than a minimum, which is predominantly determined by the resensitization time. The proposed technique provides a useful tool to systematically optimize radiotherapy for fast and slow proliferating tumors and sheds important insight into the complex problem of dose-time fractionation.

    View details for DOI 10.1118/1.2126167

    View details for Web of Science ID 000234643700018

    View details for PubMedID 16475766

  • Towards biologically conformal radiation therapy (BCRT): Selective IMRT dose escalation under the guidance of spatial biology distribution MEDICAL PHYSICS Yang, Y., Xing, L. 2005; 32 (6): 1473-1484

    Abstract

    It is well known that the spatial biology distribution (e.g., clonogen density, radiosensitivity, tumor proliferation rate, functional importance) in most tumors and sensitive structures is heterogeneous. Recent progress in biological imaging is making the mapping of this distribution increasingly possible. The purpose of this work is to establish a theoretical framework to quantitatively incorporate the spatial biology data into intensity modulated radiation therapy (IMRT) inverse planning. In order to implement this, we first derive a general formula for determining the desired dose to each tumor voxel for a known biology distribution of the tumor based on a linear-quadratic model. The desired target dose distribution is then used as the prescription for inverse planning. An objective function with the voxel-dependent prescription is constructed with incorporation of the nonuniform dose prescription. The functional unit density distribution in a sensitive structure is also considered phenomenologically when constructing the objective function. Two cases with different hypothetical biology distributions are used to illustrate the new inverse planning formalism. For comparison, treatments with a few uniform dose prescriptions and a simultaneous integrated boost are also planned. The biological indices, tumor control probability (TCP) and normal tissue complication probability (NTCP), are calculated for both types of plans and the superiority of the proposed technique over the conventional dose escalation scheme is demonstrated. Our calculations revealed that it is technically feasible to produce deliberately nonuniform dose distributions with consideration of biological information. Compared with the conventional dose escalation schemes, the new technique is capable of generating biologically conformal IMRT plans that significantly improve the TCP while reducing or keeping the NTCPs at their current levels. Biologically conformal radiation therapy (BCRT) incorporates patient-specific biological information and provides an outstanding opportunity for us to truly individualize radiation treatment. The proposed formalism lays a technical foundation for BCRT and allows us to maximally exploit the technical capacity of IMRT to more intelligently escalate the radiation dose.

    View details for Web of Science ID 000229908600004

    View details for PubMedID 16013703

  • Measurement of ionizing radiation using carbon nanotube field effect transistor PHYSICS IN MEDICINE AND BIOLOGY Tang, X. W., Yang, Y., Kim, W., Wang, Q., Qi, P. F., Dai, H. J., Xing, L. 2005; 50 (3): N23-N31

    Abstract

    Single-walled carbon nanotubes (SWNTs) are a new class of highly promising nanomaterials for future nano-electronics. Here, we present an initial investigation of the feasibility of using SWNT field effect transistors (SWNT-FETs) formed on silicon-oxide substrates and suspended FETs for radiation dosimetry applications. Electrical measurements and atomic force microscopy (AFM) revealed the intactness of SWNT-FET devices after exposure to over 1 Gy of 6 MV therapeutic x-rays. The sensitivity of SWNT-FET devices to x-ray irradiation is elucidated by real-time dose monitoring experiments and accumulated dose reading based on threshold voltage shift. SWNT-FET devices exhibit sensitivities to x-rays that are at least comparable to or orders of magnitude higher than commercial MOSFET (metal-oxide semiconductor field effect transistor) dosimeters and could find applications as miniature dosimeters for microbeam profiling and implantation.

    View details for DOI 10.1088/0031-9155/50/3/N02

    View details for PubMedID 15773731

  • Clinical knowledge-based inverse treatment planning PHYSICS IN MEDICINE AND BIOLOGY Yang, Y., Xing, L. 2004; 49 (22): 5101-5117

    Abstract

    Clinical IMRT treatment plans are currently made using dose-based optimization algorithms, which do not consider the nonlinear dose-volume effects for tumours and normal structures. The choice of structure specific importance factors represents an additional degree of freedom of the system and makes rigorous optimization intractable. The purpose of this work is to circumvent the two problems by developing a biologically more sensible yet clinically practical inverse planning framework. To implement this, the dose-volume status of a structure was characterized by using the effective volume in the voxel domain. A new objective function was constructed with the incorporation of the volumetric information of the system so that the figure of merit of a given IMRT plan depends not only on the dose deviation from the desired distribution but also the dose-volume status of the involved organs. The conventional importance factor of an organ was written into a product of two components: (i) a generic importance that parametrizes the relative importance of the organs in the ideal situation when the goals for all the organs are met; (ii) a dose-dependent factor that quantifies our level of clinical/dosimetric satisfaction for a given plan. The generic importance can be determined a priori, and in most circumstances, does not need adjustment, whereas the second one, which is responsible for the intractable behaviour of the trade-off seen in conventional inverse planning, was determined automatically. An inverse planning module based on the proposed formalism was implemented and applied to a prostate case and a head-neck case. A comparison with the conventional inverse planning technique indicated that, for the same target dose coverage, the critical structure sparing was substantially improved for both cases. The incorporation of clinical knowledge allows us to obtain better IMRT plans and makes it possible to auto-select the importance factors, greatly facilitating the inverse planning process. The new formalism proposed also reveals the relationship between different inverse planning schemes and gives important insight into the problem of therapeutic plan optimization. In particular, we show that the EUD-based optimization is a special case of the general inverse planning formalism described in this paper.

    View details for DOI 10.1088/0031-9155/49/22/006

    View details for Web of Science ID 000225629200006

    View details for PubMedID 15609561

  • Inverse treatment planning with adaptively evolving voxel-dependent penalty scheme MEDICAL PHYSICS Yong, Y., Lei, X. 2004; 31 (10): 2839-2844

    Abstract

    In current inverse planning algorithms it is common to treat all voxels within a target or sensitive structure equally and use structure specific prescriptions and weighting factors as system parameters. In reality, the voxels within a structure are not identical in complying with their dosimetric goals and there exists strong intrastructural competition. Inverse planning objective function should not only balance the competing objectives of different structures but also that of the individual voxels in various structures. In this work we propose to model the intrastructural tradeoff through the modulation of voxel-dependent importance factors and deal with the challenging problem of how to obtain a sensible set of importance factors with a manageable amount of computing. Instead of letting the values of voxel-dependent importance to vary freely during the search process, an adaptive algorithm, in which the importance factors were tied to the local radiation doses through a heuristically constructed relation, was developed. It is shown that the approach is quite general and the EUD-based optimization is a special case of the proposed framework. The new planning tool was applied to study a hypothetical phantom case and a prostate case. Comparison of the results with that obtained using conventional inverse planning technique with structure specific importance factors indicated that the dose distributions from the conventional inverse planning are at best suboptimal and can be significantly improved with the help of the proposed nonuniform penalty scheme.

    View details for DOI 10.1118/1.1799311

    View details for Web of Science ID 000224743200017

    View details for PubMedID 15543792

  • Quantitative measurement of MLC leaf displacements using an electronic portal image device 45th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) Yang, Y., Xing, L. IOP PUBLISHING LTD. 2004: 1521?33

    Abstract

    The success of an IMRT treatment relies on the positioning accuracy of the MLC (multileaf collimator) leaves for both step-and-shoot and dynamic deliveries. In practice, however, there exists no effective and quantitative means for routine MLC QA and this has become one of the bottleneck problems in IMRT implementation. In this work we present an electronic portal image device (EPID) based method for fast and accurate measurement of MLC leaf positions at arbitrary locations within the 40 cm x 40 cm radiation field. The new technique utilizes the fact that the integral signal in a small region of interest (ROI) is a sensitive and reliable indicator of the leaf displacement. In this approach, the integral signal at a ROI was expressed as a weighted sum of the contributions from the displacements of the leaf above the point and the adjacent leaves. The weighting factors or linear coefficients of the system equations were determined by fitting the integral signal data for a group of pre-designed MLC leaf sequences to the known leaf displacements that were intentionally introduced during the creation of the leaf sequences. Once the calibration is done, the system can be used for routine MLC leaf positioning QA to detect possible leaf errors. A series of tests was carried out to examine the functionality and accuracy of the technique. Our results show that the proposed technique is potentially superior to the conventional edge-detecting approach in two aspects: (i) it deals with the problem in a systematic approach and allows us to take into account the influence of the adjacent MLC leaves effectively; and (ii) it may improve the signal-to-noise ratio and is thus capable of quantitatively measuring extremely small leaf positional displacements. Our results indicate that the technique can detect a leaf positional error as small as 0.1 mm at an arbitrary point within the field in the absence of EPID set-up error and 0.3 mm when the uncertainty is considered. Given its simplicity, efficiency and accuracy, we believe that the technique is ideally suitable for routine MLC leaf positioning QA.

    View details for DOI 10.1088/0031-9155/49/8/010

    View details for Web of Science ID 000221250800010

    View details for PubMedID 15152689

  • Incorporating leaf transmission and head scatter corrections into step-and-shoot leaf sequences for IMRT INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Yang, Y., Xing, L. 2003; 55 (4): 1121-1134

    Abstract

    Leaf transmission and head scatter are two important factors that influence intensity-modulated radiation therapy (IMRT) delivery and should be correctly taken into account when generating multileaf collimator (MLC) sequences. Significant discrepancies between the desired and delivered intensity profiles could otherwise result. The purpose of this article is to propose a reliable algorithm to minimize the dosimetric effects caused by the two factors in step-and-shoot mode.The goal of the algorithm is to minimize the difference between the desired fluence map and the fluence map actually delivered. For this purpose, an error function, defined as the least-square difference between the desired and the delivered fluence maps, is introduced. The effects of transmission and head scatter are minimized by adjusting the fractional monitor units (MUs) in the initial MLC sequences, created by using the desired fluence map without inclusion of the contributions from the two factors. Computationally, a downhill simplex optimization method is used to minimize the error function with respect to the fractional MUs. A three-source model is used to evaluate the relative head scatter distribution for each segment at the beginning of the calculation. The algorithm has been assessed by comparing the dose distributions delivered by the corrected leaf sequence files and the theoretic predication, calculated by Monte Carlo simulation using the desired fluence maps, for an intuitive test field and several clinical IMRT cases.The deviations between the desired fluence maps and those calculated using the corrected leaf sequence files are <0.3% of the maximum MU for the test field and <1.0% for the clinical IMRT cases. The experimental data show that both absolute and relative dose distributions delivered by the corrected leaf sequences agree with the desired ones within 2.5% of the maximum dose or 2 mm in high-dose gradient regions. Compared with the results obtained by using the leaf sequences in which only the transmission or none of the two effects is corrected, significant improvements in the fluence and dose distributions have been observed.Transmission and head scatter play important roles in the dosimetric behavior of IMRT delivery. A larger error may result if only one factor is considered because of the opposite effects of the two factors. We noted that the influence of the two effects is more pronounced in absolute dose than in the relative dose. The algorithm proposed in this work accurately corrects for these two effects in step-and-shoot delivery and provides a reliable tool for clinical IMRT application.

    View details for DOI 10.1016/S0360-3016(02)04417-6

    View details for Web of Science ID 000181269600031

    View details for PubMedID 12605992

  • Using the volumetric effect of a finite-sized detector for routine quality assurance of multileaf collimator leaf positioning MEDICAL PHYSICS Yang, Y., Xing, L. 2003; 30 (3): 433-441

    Abstract

    Intensity modulated radiation therapy (IMRT) is an advanced form of radiation therapy and promises to improve dose conformation while reducing the irradiation to the sensitive structures. The modality is, however, more complicated than conventional treatment and requires much more stringent quality assurance (QA) to ensure what has been planned can be achieved accurately. One of the main QA tasks is the assurance of positioning accuracy of multileaf collimator (MLC) leaves during IMRT delivery. Currently, the routine quality assurance of MLC in most clinics isbeing done using radiographic films with specially designed MLC leaf sequences. Besides being time consuming, the results of film measurements are difficult to quantify and interpret. In this work, we propose a new and effective technique for routine MLC leaf positioning QA. The technique utilizes the fact that, when a finite-sized detector is placed under a leaf, the relative output of the detector will depend on the relative fractional volume irradiated. A small error in leaf positioning would change the fractional volume irradiated and lead to a deviation of the relative output from the normal reading. For a given MLC and detector system, the relation between the relative output and the leaf displacement can be easily established through experimental measurements and used subsequently as a quantitative means for detecting possible leaf positional errors. The method was tested using a linear accelerator with an 80-leaf MLC. Three different locations, including two locations on central plane (X1 = X2 = 0) and one point on an off-central plane location (X1 = -7.5, X = 7.5), were studied. Our results indicated that the method could accurately detect a leaf positional change of approximately 0.1 mm. The method was also used to monitor the stability of MLC leaf positioning for five consecutive weeks. In this test, we intentionally introduced two positional errors in the testing MLC leaf sequences: -0.2 mm and 1.2 mm. The technique was found to be robust and could detect the positional inaccuracy in each week's test. The influence of other possible error sources, including the ion chamber placement, jaw settings, gantry and collimator angle read-outs, and the positioning errors of the adjacent leaves, on detection accuracy were also investigated. The principle of our method is independent of the types of the MLC and the detector and may have significant practical implications in facilitating routine MLC QA for IMRT delivery.

    View details for DOI 10.1118/1.1543150

    View details for Web of Science ID 000181587500019

    View details for PubMedID 12674244

  • A three-source model for the calculation of head scatter factors MEDICAL PHYSICS Yang, Y., Xing, L., Boyer, A. L., Song, Y. X., Hu, Y. M. 2002; 29 (9): 2024-2033

    Abstract

    Accurate determination of the head scatter factor Sc is an important issue, especially for intensity modulated radiation therapy, where the segmented fields are often very irregular and much less than the collimator jaw settings. In this work, we report an Sc calculation algorithm for symmetric, asymmetric, and irregular open fields shaped by the tertiary collimator (a multileaf collimator or blocks) at different source-to-chamber distance. The algorithm was based on a three-source model, in which the photon radiation to the point of calculation was treated as if it originated from three effective sources: one source for the primary photons from the target and two extra-focal photon sources for the scattered photons from the primary collimator and the flattening filter, respectively. The field mapping method proposed by Kim et al. [Phys. Med. Biol. 43, 1593-1604 (1998)] was extended to two extra-focal source planes and the scatter contributions were integrated over the projected areas (determined by the detector's eye view) in the three source planes considering the source intensity distributions. The algorithm was implemented using Microsoft Visual C/C++ in the MS Windows environment. The only input data required were head scatter factors for symmetric square fields, which are normally acquired during machine commissioning. A large number of different fields were used to evaluate the algorithm and the results were compared with measurements. We found that most of the calculated Sc's agreed with the measured values to within 0.4%. The algorithm can also be easily applied to deal with irregular fields shaped by a multileaf collimator that replaces the upper or lower collimator jaws.

    View details for DOI 10.1118/1.1500767

    View details for Web of Science ID 000178093000010

    View details for PubMedID 12349923

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