Estimation of the delivered patient dose in lung IMRT treatment based on deformable registration of 4D-CT data and Monte Carlo simulations

The purpose of this study is to accurately estimate the difference between the planned and the delivered dose due to respiratory motion and free breathing helical CT artefacts for lung IMRT treatments, and to estimate the impact of this difference on clinical outcome. Six patients with representative tumour motion, size and position were selected for this retrospective study. For each patient, we had acquired both a free breathing helical CT and a ten-phase 4D-CT scan. A commercial treatment planning system was used to create four IMRT plans for each patient. The first two plans were based on the GTV as contoured on the free breathing helical CT set, with a GTV to PTV expansion of 1.5 cm and 2.0 cm, respectively. The third plan was based on the ITV, a composite volume formed by the union of the CTV volumes contoured on free breathing helical CT, end-of-inhale (EOI) and end-of-exhale (EOE) 4D-CT. The fourth plan was based on GTV contoured on the EOE 4D-CT. The prescribed dose was 60 Gy for all four plans. Fluence maps and beam setup parameters of the IMRT plans were used by the Monte Carlo dose calculation engine MCSIM for absolute dose calculation on both the free breathing CT and 4D-CT data. CT deformable registration between the breathing phases was performed to estimate the motion trajectory for both the tumour and healthy tissue. Then, a composite dose distribution over the whole breathing cycle was calculated as a final estimate of the delivered dose. EUD values were computed on the basis of the composite dose for all four plans. For the patient with the largest motion effect, the difference in the EUD of CTV between the planed and the delivered doses was 33, 11, 1 and 0 Gy for the first, second, third and fourth plan, respectively. The number of breathing phases required for accurate dose prediction was also investigated. With the advent of 4D-CT, deformable registration and Monte Carlo simulations, it is feasible to perform an accurate calculation of the delivered dose, and compare our delivered dose with doses estimated using prior techniques.     

On the automated definition of mobile target volumes from 4D-CT images for stereotactic body radiotherapy

Stereotactic body radiotherapy (SBRT) can be used to treat small lesions in the chest. A vacuum-based immobilization system is used in our clinic for SBRT, and a motion envelope is used in treatment planning. The purpose of this study is to automatically derive motion envelopes using deformable image registration of 4D-CT images, and to assess the effect of abdominal pressure on the motion envelopes. 4D-CT scans at ten phases were acquired prior to treatment for both free and restricted breathing using a vacuum-based immobilization system that includes an abdominal pressure pillow. To study the stability of the motion envelope over the course of treatment, a mid-treatment 4D-CT scan was obtained after delivery of the third fraction for two patients. The planning target volume excluding breathing motion (PTV(ex)) was defined on the image set at full exhalation phase and transformed into all other phases using displacement maps from deformable image registration. The motion envelope was obtained as the union of PTV(ex) masks of all phases. The ratios of the motion envelope to PTV(ex) volume ranged from 1.3 to 2.5. When pressure was applied, the ratios were reduced by as much as 29% compared to free breathing for some patients, but increased by up to 9% for others. The abdominal pressure pillow has more motion restriction effects on the anterior/inferior region of the lung. For one of the two patients for whom the 4D-CT scan was repeated at mid-treatment, the motion envelope was reproducible. However, for the other patient the tumor location and lung motion pattern significantly changed due to changes in the anatomy surrounding the tumor during the course of treatment, indicating that an image-guided approach to SBRT may increase the efficacy of this treatment.     

A novel four-dimensional radiotherapy method for lung cancer: imaging, treatment planning and delivery

We present treatment planning methods based on four-dimensional computed tomography (4D-CT) to incorporate tumour motion using (1) a static field and (2) a dynamic field. Static 4D fields are determined to include the target in all breathing phases, whereas dynamic 4D fields are determined to follow the shape of the tumour assessed from 4D-CT images with a dynamic weighting factor. The weighting factor selection depends on the reliability of patient breathing and limitations of the delivery system. The static 4D method is compared with our standard protocol for gross tumour volume (GTV) coverage, mean lung dose and V20. It was found that the GTV delineated on helical CT without incorporating breathing motion does not adequately represent the target compared to the GTV delineated from 4D-CT. Dosimetric analysis indicates that the static 4D-CT based technique results in a reduction of the mean lung dose compared with the standard protocol. Measurements on a moving phantom and simulations indicated that 4D radiotherapy (4D-RT) synchronized with respiration-induced motion further reduces mean lung dose and V20, and may allow safe application of dose escalation and CRT/IMRT. The motions of the chest cavity, tumour and thoracic structures of 24 lung cancer patients are also analysed.     

Planning lung radiotherapy using 4D CT data and a motion model

This work is a feasibility study to use a four-dimensional computed tomography (4D CT) dataset generated by a continuous motion model for treatment planning in lung radiotherapy. The model-based 4D CT data were derived from multiple breathing cycles. Four patients were included in this retrospective study. Treatment plans were optimized at end-exhale for each patient and the effect of respiratory motion on the dose delivery investigated. The accuracy of the delivered dose as determined by the number of intermediate respiratory phases used for the calculation was considered. The time-averaged geometry of the anatomy representing the mid-ventilation phase of the breathing cycle was generated using the motion model and a treatment plan was optimized for this phase for one patient. With respiratory motion included, the mid-ventilation plan achieved better target coverage than the plan optimized at end-exhale when standard margins were used to expand the clinical target volume (CTV) to planning target volume (PTV). Using a margin to account for set-up uncertainty only, resulted in poorer target coverage and healthy tissue sparing. For this patient cohort, the results suggest that conventional three-dimensional treatment planning was sufficient to maintain target coverage despite respiratory motion. The motion model has proved a useful tool in 4D treatment planning.     

Use of high-frequency ultrasound imaging to improve delineation of anterior uveal melanoma for proton irradiation

The aim of this study was to evaluate high-frequency ultrasound imaging (HFUI) as an aid in localizing anterior margins of tumours of the eye for proton therapy. Proton irradiation of ocular melanoma requires an accurate assessment of all tumour margins. The tumour is marked surgically by suturing to the sclera four or five tantalum rings on the borders of the tumour defined by transillumination. In order to evaluate the clinical usefulness of high-frequency ultrasound imaging, four and five rings were surgically placed in a patient with an iris/ciliary body melanoma and in a patient with ciliochoroidal melanoma using transillumination to localize the tumour margins. Subsequently margins were verified by HFUI. In the first patient, the distances between the rings and the limbus were measured using calipers during surgery and were compared with HFUI measurements and measurements from planning software. The distances were comparable within 0.5 mm. In the second patient the treatment was planned in two different ways using EYEPLAN software. In the first scenario the shape of the tumour and its relation to the rings were obtained from the surgeon's mapping, the fundus drawing using a transilluminating point light source, and the HFUI. In the second scenario, the shape of the tumour was deduced from the ring positions only. It was observed that the maximum difference between the tumour edge as seen on high-frequency ultrasound images and the rings was 2.6 mm. The tumour volume was underestimated by 39% when tumour shape was obtained from ring positions only. During the past year we have utilized HFUI in 18 patients having tumours involving the anterior segment of the eye, among which four were treated with proton therapy. In conclusion, we believe that high-frequency ultrasound imaging provides additional information with respect to the location of tumour margins in ciliary body and anterior uveal melanoma. Occult extension of the tumour within the ciliary body or posterior iris may not be appreciated by transillumination alone.     

Acquiring 4D thoracic CT scans using a multislice helical method

Respiratory motion degrades anatomic position reproducibility during imaging, necessitates larger margins during radiotherapy planning and causes errors during radiation delivery. Computed tomography (CT) scans acquired synchronously with the respiratory signal can be used to reconstruct 4D CT scans, which can be employed for 4D treatment planning to explicitly account for respiratory motion. The aim of this research was to develop, test and clinically implement a method to acquire 4D thoracic CT scans using a multislice helical method. A commercial position-monitoring system used for respiratory-gated radiotherapy was interfaced with a third generation multislice scanner. 4D cardiac reconstruction methods were modified to allow 4D thoracic CT acquisition. The technique was tested on a phantom under different conditions: stationary, periodic motion and non-periodic motion. 4D CT was also implemented for a lung cancer patient with audio-visual breathing coaching. For all cases, 4D CT images were successfully acquired from eight discrete breathing phases, however, some limitations of the system in terms of respiration reproducibility and breathing period relative to scanner settings were evident. Lung mass for the 4D CT patient scan was reproducible to within 2.1% over the eight phases, though the lung volume changed by 20% between end inspiration and end expiration (870 cm3). 4D CT can be used for 4D radiotherapy, respiration-gated radiotherapy, 'slow' CT acquisition and tumour motion studies.     

Planning evaluation of radiotherapy for complex lung cancer cases using helical tomotherapy

Lung cancer treatment is one of the most challenging fields in radiotherapy. The aim of the present study was to investigate what role helical tomotherapy (HT), a novel approach to the delivery of highly conformal dose distributions using intensity-modulated radiation fan beams, can play in difficult cases with large target volumes typical for many of these patients. Tomotherapy plans were developed for 15 patients with stage III inoperable non-small-cell lung cancer. While not necessarily clinically indicated, elective nodal irradiation was included for all cases to create the most challenging scenarios with large target volumes. A 2 cm margin was used around the gross tumour volume (GTV) to generate primary planning target volume (PTV2) and 1 cm margin around elective nodes for secondary planning target volume (PTV1) resulting in PTV1 volumes larger than 1000 cm3 in 13 of the 15 patients. Tomotherapy plans were created using an inverse treatment planning system (TomoTherapy Inc.) based on superposition/convolution dose calculation for a fan beam thickness of 25 mm and a pitch factor between 0.3 and 0.8. For comparison, plans were created using an intensity-modulated radiation therapy (IMRT) approach planned on a commercial treatment planning system (TheraplanPlus, Nucletron). Tomotherapy delivery times for the large target volumes were estimated to be between 4 and 19 min. Using a prescribed dose of 60 Gy to PTV2 and 46 Gy to PTV1, the mean lung dose was 23.8+/-4.6 Gy. A 'dose quality factor' was introduced to correlate the plan outcome with patient specific parameters. A good correlation was found between the quality of the HT plans and the IMRT plans with HT being slightly better in most cases. The overlap between lung and PTV was found to be a good indicator of plan quality for HT. The mean lung dose was found to increase by approximately 0.9 Gy per percent overlap volume. Helical tomotherapy planning resulted in highly conformal dose distributions. It allowed easy achievement of two different dose levels in the target simultaneously. As the overlap between PTV and lung volume is a major predictor of mean lung dose, future work will be directed to control of margins. Work is underway to investigate the possibility of breath-hold techniques for tomotherapy delivery to facilitate this aim.     

An optimized workflow for the integration of biological information into radiotherapy planning: experiences with T1w DCE-MRI

Planning of radiotherapy is often difficult due to restrictions on morphological images. New imaging techniques enable the integration of biological information into treatment planning and help to improve the detection of vital and aggressive tumour areas. This might improve clinical outcome. However, nowadays morphological data sets are still the gold standard in the planning of radiotherapy. In this paper, we introduce an in-house software platform enabling us to combine images from different imaging modalities yielding biological and morphological information in a workflow driven approach. This is demonstrated for the combination of morphological CT, MRI, functional DCE-MRI and PET data. Data of patients with a tumour of the prostate and with a meningioma were examined with DCE-MRI by applying pharmacokinetic two-compartment models for post-processing. The results were compared with the clinical plans for radiation therapy. Generated parameter maps give additional information about tumour spread, which can be incorporated in the definition of safety margins.     

Population and patient-specific target margins for 4D adaptive radiotherapy to account for intra- and inter-fraction variation in lung tumour position

In this work, five 4D image-guidance strategies (two population, an offline adaptive and two online strategies) were evaluated that compensated for both inter- and intra-fraction variability such as changes to the baseline tumour position and respiratory pattern. None of the strategies required active motion compensation such as gating or tracking; all strategies simulated a free-breathing-based treatment technique. Online kilovoltage fluoroscopy was acquired for eight patients with lung tumours, and used to construct inter- and intra-fraction tumour position variability models. Planning was performed on a mid-ventilation image acquired from a respiration-correlated CT scan. The blurring effect of tumour position variability was included in the dose calculation by convolution. CTV to PTV margins were calculated for variability in the cranio-caudal direction. A population margin of 9.0 +/- 0.7 mm was required to account for setup error and respiration in the study population without the use of image-guidance. The greatest mean margin reduction was introduced by the offline adaptive strategy. A daily online correction strategy produced a small reduction (1.6 mm) in the mean margin from the offline strategy. Adaptively correcting for an inter-fraction change in the respiratory pattern had little effect on margin size due to most patients having only small daily changes in the respiratory pattern. A daily online correction strategy would be useful for patients who exhibit large variations in the daily mean tumour position, while an offline adaptive strategy is more applicable to patients with less variation.     

基于4D-CT和Mimics软件模拟分析肺癌肿瘤的呼吸运动规律

目的：利用Mimics10.01软件和4D-CT10个呼吸时相的肺部三维模型,研究肺部肿瘤的呼吸运动规律。方法：选择1例左上肺癌患者,在肿瘤上、中、下部植入3个金标,间隔为6 mm,4D-CT扫描相位排序后重建10个呼吸时相的CT图像。将10个时相的CT图像依次导入Mimics10.01软件中,采用阈值分割、区域生长的方法提取肺部区域,重建左右肺的三维模型。测量10个呼吸时相的左右肺体积和表面积;吸气末与呼气末时相之间左肺三维模型之间的偏差也进行了分析。在每个时相的CT图像上读取植入3个金标的位置坐标,求出金标在X、Y、Z方向上质心的坐标。结果：从吸气末到呼气末左、右肺体积的变化范围分别为12.8%和12.4%,左、右肺表面积的变化范围为6.6%和6.7%。3个金标的质心变化幅度在左右、头脚、前后方向分别为2 mm,1mm和2.7 mm。结论：利用4D-CT的图像和Mimics软件重建得出的肺模型可以方便地计算肺体积以及靶区的运动范围,有利于根据患者的靶区运动特征实现个体化治疗。     

Quantifying ITV instabilities arising from 4DCT: a simulation study using patient data

Treatment planning for patients undergoing radiation therapy is often performed based on four-dimensional computed tomography (4DCT) when respiratory motion is present, as in lung cancer patients. 4DCT is used to define the internal target volume (ITV) that, ideally, incorporates all potential locations of the tumour. In this work, we use the locations of gold fiducial markers implanted in lung tumours of eight patients to represent tumour motion. These fiducial locations are used in a simulation of a four-slice CT scanner to generate the ITV for 10, 20 and 30 mm diameter model tumours. To demonstrate instabilities in the ITV definition based on 4DCT, the ITV calculation was repeated for the same patients for consecutive scan start times, staggered by 1 s. The volumetric difference in the ITV and the per cent of time that the ITV contains in the tumour are both evaluated. The ITV from a single patient was found to vary by 46%-127% for a tumour diameter of 10 mm. The ITV did not cover the entirety of the tumour 11%-74% of the time for a 10 mm tumour diameter.     

Variation in target and rectum dose due to prostate deformation: an assessment by repeated MR imaging and treatment planning

In daily clinical practice, implanted fiducial markers are used to correct for prostate motion, but not for prostate deformation. The aim of this study is to investigate the variation in target and rectum dose due to the deformation of the prostate gland (without seminal vesicles). Therefore, we performed five to six MRI scans of eight healthy volunteers that exhibited large variation in rectal volume and thus prostate deformation. Prostate motion was corrected by a mask-based rigid registration which uses the delineation as well as the internal structures of the prostate gland. Per MRI scan, one IMRT plan with a PTV margin of 4 mm was created, resulting in 41 IMRT plans. The dose distribution of the IMRT plan based on the MRI scan with the minimum rectal volume was applied to the other rigidly registered MRI scans to evaluate the impact of prostate deformation. In conclusion, pre-treatment planning on the minimum rectal volume can cause a fraction dose increase (up to 15%) to the rectum due to prostate deformation. The impact on the total dose increase to the rectum depends on the intrapatient rectum variation during treatment, but is negligible with the currently used PTV margins in a fractionated treatment.     

Absolute and relative dose-surface and dose-volume histograms of the bladder: which one is the most representative for the actual treatment?

The purpose of this study was to quantify to what extent relative and absolute bladder dose-volume and dose-surface histograms of the planning CT scan were representative for the actual treatment. We used data of 17 patients, who each received 11 repeat CT scans and a planning CT scan. The repeat CT scans were matched on the planning CT scan by the bony anatomy. Clinical treatment plans were used to evaluate the impact of bladder filling changes on the four histogram types. The impact was quantified by calculating for this patient group the correlation coefficient between the planning histogram and the treatment histogram. We found that the absolute dose-surface histogram was the most representative one for the actual treatment.     

Dosimetric evaluation of MRI-based treatment planning for prostate cancer

The purpose of this study is to evaluate the dosimetric accuracy of MRI-based treatment planning for prostate cancer using a commercial radiotherapy treatment planning system. Three-dimensional conformal plans for 15 prostate patients were generated using the AcQPlan system. For each patient, dose distributions were calculated using patient CT data with and without heterogeneity correction, and using patient MRI data without heterogeneity correction. MR images were post-processed using the gradient distortion correction (GDC) software. The distortion corrected MR images were fused to the corresponding CT for each patient for target and structure delineation. The femoral heads were delineated based on CT. Other anatomic structures relevant to the treatment (i.e., prostate, seminal vesicles, lymph notes, rectum and bladder) were delineated based on MRI. The external contours were drawn separately on CT and MRI. The same internal contours were used in the dose calculation using CT- and MRI-based geometries by directly transferring them between MRI and CT as needed. Treatment plans were evaluated based on maximum dose, isodose distributions and dose-volume histograms. The results confirm previous investigations that there is no clinically significant dose difference between CT-based prostate plans with and without heterogeneity correction. The difference in the target dose between CT- and MRI-based plans using homogeneous geometry was within 2.5%. Our results suggest that MRI-based treatment planning is suitable for radiotherapy of prostate cancer.     

基于4D-CT研究随呼吸运动靶区的剂量分布规律

目的:基于4D-CT探讨随呼吸运动靶区的受照剂量分布特征及进行个体化精确放疗计划设计方法。材料和方法:患者在自由呼吸状态下进行多床位Cine模式扫描,每个床位Cine扫描持续时间约4s～6s。扫描后,用研究开发的4D-CT图像重建系统对所得图像进行4D-CT、最大密度投影(MIP)和平均密度投影(AIP)重建,生成多相位4D-CT、MIP和AIPCT。将重建图像传入放疗计划系统中,分别以呼气末相4D-CT、AIPCT和MIPCT图像作为基准图像,其它相位4D-CT作为融合图像进行图像配准,在基准图像上勾画靶区并进行放疗计划设计,比较基准图像和融合图像中靶区的剂量分布。结果:当肿瘤靶区位于肺尖时,呼气末相和吸气末相4D-CT中靶区的剂量分布无明显差异;靶区在肺中部和腹部时,在呼气末相4D-CT上设计的放疗计划,其剂量分布不能很好地覆盖吸气末相时的靶区,可能导致靶区漏照射;在MIP和AIPCT上设计的放疗计划,其剂量分布能较好地覆盖呼气末相/吸气末相时的靶区。结论:基于4D-CT能直观地得到不同呼吸相位时靶区的剂量分布,利用MIP和AIPCT可快速实现运动靶区的个体化精确放疗计划设计。     

Improvement of the cine-CT based 4D-CT imaging

An improved 4D-CT utility has been developed on the GE LightSpeed multislice CT (MSCT) and Discovery PET/CT scanners, which have the cine CT scan capability. Two new features have been added in this 4D-CT over the commercial Advantage 4D-CT from GE. One feature was a new tool for disabling parts of the respiratory signal with irregular respiration and improving the accuracy of phase determination for the respiratory signal from the Varian real-time positioning and monitoring (RPM) system before sorting of the cine CT images into the 4D-CT images. The second feature was to allow generation of the maximum-intensity-projection (MIP), average (AVG) and minimum-intensity-projection (mip) CT images from the cine CT images without a respiratory signal. The implementation enables the assessment of tumor motion in treatment planning with the MIP, AVG, and mip CT images on the GE MSCT and PET/CT scanners without the RPM and the Advantage 4D-CT with a GE Advantage windows workstation. Several clinical examples are included to illustrate this new application.     

Four-Dimensional Computerized Tomography （4D-CT） Reconstruction Based on the Similarity Measure of Spatial Adjacent Images

Objective：To investigate the feasibility of a 4D-CT reconstruction method based on the similarity principle of spatial adjacent images and mutual information measure. Methods：A motor driven sinusoidal motion platform made in house was used to create one-dimensional periodical motion that was along the longitudinal axis of the CT couch. The amplitude of sinusoidal motion was set to an amplitude of ±1 cm. The period of the motion was adjustable and set to 3.5 s. Phantom objects of two eggs were placed in a Styrofoam block, which in turn were placed on the motion platform. These objects were used to simulate volumes of interest Undergoing ideal periodic motion. CT data of static phantom were acquired using a multi-slice general electric （GE） LightSpeed 16-slice CT scanner in an axial mode. And the CT data of periodical motion phantom were acquired in an axial and cine-mode scan. A software program was developed by using VC ＋ ＋ and VTK software tools to resort the CT data and reconstruct the 4D-CT. Then all of the CT data with same phase were sorted by the program into the same series based on the similarity principle of spatial adjacent images and mutual information measure among them, and 3D reconstruction of different phase CT data were completed by using the software. Results：All of the CT data were sorted accurately into different series based on the similarity principle of spatial adjacent images and mutual information measures among them. Compared with the unsorted CT data, the motion artifacts in the 3 D reconstruction of sorted CT data were re- duced significantly, and all of the sorted CT series result in a 4D-CT that reflected the characteristic of the periodical motion phantom. Conclusion：Time-resolved 4D-CT reconstruction can be implemented with any general multi-slice CT scanners based on the similarity principle of spatial adjacent images and mutual information measure. The process of the 4D-CT data acquisition and reconstruction were not restricted to the hardware or software of the C