Detection and compensation of organ/lesion motion using 4D-PET/CT respiratory gated acquisition techniques

Purpose

To describe the degradation effects produced by respiratory organ and lesion motion on PET/CT images and to define the role of respiratory gated (RG) 4D-PET/CT techniques to compensate for such effects.

Methods

Based on the literature and on our own experience, technical recommendations and clinical indications for the use of RG 4D PET/CT have been outlined.

Results

RG 4D-PET/CT techniques require a state of the art PET/CT scanner, a respiratory monitoring system and dedicated acquisition and processing protocols. Patient training is particularly important to obtain a regular breathing pattern. An adequate number of phases has to be selected to balance motion compensation and statistical noise. RG 4D PET/CT motion free images may be clinically useful for tumour tissue characterization, monitoring patient treatment and target definition in radiation therapy planning.

Conclusions

RG 4D PET/CT is a valuable tool to improve image quality and quantitative accuracy and to assess and measure organ and lesion motion for radiotherapy planning.     

Treatment planning for resected abdominal tumors: differences in organ position between diagnostic and radiation-planning computed tomography scans

PURPOSE: To evaluate whether organ location, determined from preoperative diagnostic computed tomography scans (CTs), accurately reflects organ location when patients are positioned for radiation therapy. METHODS AND MATERIALS: We identified patients with upper abdominal malignancies treated with surgery and/or radiation therapy. Comparisons of organ position relative to fixed bony landmarks were made among preoperative diagnostic CTs, postoperative diagnostic CTs, and radiation-planning CTs. We studied 18 patients who had CTs differing only in scanning technique, 11 patients who had CTs differing only in operative state, and 7 patients with CTs differing in both scanning technique and operative state. RESULTS: For patients with diagnostic CTs and radiation-planning CTs that were either both preoperative or both postoperative, mean organ position, measured relative to a fixed bony landmark, ranged from 1.9 to 3.2 cm superior on radiation-planning CTs compared with diagnostic CTs (p < 0.0001). Mean organ position ranged from 0.9 to 1.7 cm posterior on radiation-planning CTs compared with diagnostic CTs (p < or = 0.008). Shifts in the right-left direction were small and variable. For patients with pre- and postoperative diagnostic CTs, organ shifts were variable and not significant. Organ shifts for patients with preoperative diagnostic CTs and postoperative radiation-planning CTs were similar to shifts observed for the first group. CONCLUSIONS: Relative to bony landmarks, there are superior and posterior shifts in organ position for radiation-planning CTs compared with diagnostic CTs. These shifts should be considered during treatment planning for resected abdominal tumors.     

Daily CT localization for correcting portal errors in the treatment of prostate cancer

Introduction: Improved prostate localization techniques should allow the reduction of margins around the target to facilitate dose escalation in high-risk patients while minimizing the risk of normal tissue morbidity. A daily CT simulation technique is presented to assess setup variations in portal placement and organ motion for the treatment of localized prostate cancer.

Methods and Materials: Six patients who consented to this study underwent supine position CT simulation with an alpha cradle cast, intravenous contrast, and urethrogram. Patients received 46 Gy to the initial Planning Treatment Volume (PTV₁) in a four-field conformal technique that included the prostate, seminal vesicles, and lymph nodes as the Gross Tumor Volume (GTV₁). The prostate or prostate and seminal vesicles (GTV₂) then received 56 Gy to PTV₂. All doses were delivered in 2-Gy fractions.

After 5 weeks of treatment (50 Gy), a second CT simulation was performed. The alpha cradle was secured to a specially designed rigid sliding board. The prostate was contoured and a new isocenter was generated with appropriate surface markers. Prostate-only treatment portals for the final conedown (GTV₃) were created with a 0.25-cm margin from the GTV to PTV. On each subsequent treatment day, the patient was placed in his cast on the sliding board for a repeat CT simulation. The daily isocenter was recalculated in the anterior/posterior (A/P) and lateral dimension and compared to the 50-Gy CT simulation isocenter. Couch and surface marker shifts were calculated to produce portal alignment. To maintain proper positioning, the patients were transferred to a stretcher while on the sliding board in the cast and transported to the treatment room where they were then transferred to the treatment couch. The patients were then treated to the corrected isocenter. Portal films and electronic portal images were obtained for each field.

Results: Utilizing CT–CT image registration (fusion) of the daily and 50-Gy baseline CT scans, the isocenter changes were quantified to reflect the contribution of positional (surface marker shifts) error and absolute prostate motion relative to the bony pelvis. The maximum daily A/P shift was 7.3 mm. Motion was less than 5 mm in the remaining patients and the overall mean magnitude change was 2.9 mm. The overall variability was quantified by a pooled standard deviation of 1.7 mm. The maximum lateral shifts were less than 3 mm for all patients. With careful attention to patient positioning, maximal portal placement error was reduced to 3 mm.

Conclusion: In our experience, prostate motion after 50 Gy was significantly less than previously reported. This may reflect early physiologic changes due to radiation, which restrict prostate motion. This observation is being tested in a separate study. Intrapatient and overall population variance was minimal. With daily isocenter correction of setup and organ motion errors by CT imaging, PTV margins can be significantly reduced or eliminated. We believe this will facilitate further dose escalation in high-risk patients with minimal risk of increased morbidity. This technique may also be beneficial in low-risk patients by sparing more normal surrounding tissue.     

4D Proton treatment planning strategy for mobile lung tumors

PURPOSE: To investigate strategies for designing compensator-based 3D proton treatment plans for mobile lung tumors using four-dimensional computed tomography (4DCT) images. METHODS AND MATERIALS: Four-dimensional CT sets for 10 lung cancer patients were used in this study. The internal gross tumor volume (IGTV) was obtained by combining the tumor volumes at different phases of the respiratory cycle. For each patient, we evaluated four planning strategies based on the following dose calculations: (1) the average (AVE) CT; (2) the free-breathing (FB) CT; (3) the maximum intensity projection (MIP) CT; and (4) the AVE CT in which the CT voxel values inside the IGTV were replaced by a constant density (AVE_RIGTV). For each strategy, the resulting cumulative dose distribution in a respiratory cycle was determined using a deformable image registration method. RESULTS: There were dosimetric differences between the apparent dose distribution, calculated on a single CT dataset, and the motion-corrected 4D dose distribution, calculated by combining dose distributions delivered to each phase of the 4DCT. The AVE_RIGTV plan using a 1-cm smearing parameter had the best overall target coverage and critical structure sparing. The MIP plan approach resulted in an unnecessarily large treatment volume. The AVE and FB plans using 1-cm smearing did not provide adequate 4D target coverage in all patients. By using a larger smearing value, adequate 4D target coverage could be achieved; however, critical organ doses were increased. CONCLUSION: The AVE_RIGTV approach is an effective strategy for designing proton treatment plans for mobile lung tumors.     

Design of 4D treatment planning target volumes

PURPOSE: When using non-patient-specific treatment planning margins, respiratory motion may lead to geometric miss of the target while unnecessarily irradiating normal tissue. Imaging different respiratory states of a patient allows patient-specific target design. We used four-dimensional computed tomography (4DCT) to characterize tumor motion and create treatment volumes in 10 patients with lung cancer. These were compared with standard treatment volumes. METHODS AND MATERIALS: Four-dimensional CT and free breathing helical CT data of 10 patients were acquired. Gross target volumes (GTV) were delineated on the helical scan as well as on each phase of the 4D data. Composite GTVs were defined on 4DCT. Planning target volumes (PTV) including clinical target volume, internal margin (IM), and setup margin were generated. 4DPTVs with different IMs and standard PTVs were compared by computing centroid positions, volumes, volumetric overlap, and bounding boxes. RESULTS: Four-dimensional PTVs and conventional PTVs differed in volume and centroid positions. Overlap between 4DPTVs generated from two extreme tumor positions only compared with 10 respiratory phases was 93.7%. Comparing PTVs with margins of 15 mm (IM 5 mm) on composite 4D target volumes to PTVs with 20 mm (IM 10 mm) on helical CT data resulted in a decrease in target volume sizes by 23% on average. CONCLUSION: With patient-specific characterization of tumor motion, it should be possible to decrease internal margins. Patient-specific treatment volumes can be generated using extreme tumor positions on 4DCT. To date, more than 150 patients have been treated using 4D target design.     

4D-MRI analysis of lung tumor motion in patients with hemidiaphragmatic paralysis

Purpose

To investigate the complex breathing patterns in patients with hemidiaphragmatic paralysis due to malignant infiltration using four-dimensional magnetic resonance imaging (4D-MRI).

Patients and methods

Seven patients with bronchial carcinoma infiltrating the phrenic nerve were examined using 1.5 T MRI. The motion of the tumor and of both hemi-diaphragms were measured on dynamic 2D TrueFISP and 4D FLASH MRI sequences.

Results

For each patient, 3-6 breathing cycles were recorded. The respiratory-induced mean cranio-caudal displacement of the tumor was 6.6 mm (±2.8 SD). The mean displacement anterior-posterior was 7.4 mm (±2.6), while right-left movement was about 7.4 mm (±4.5). The mediastinum moved sidewards during inspiration, realizing a “mediastinal shift”. The paralyzed hemidiaphragm and the tumor showed a paradox motion during respiration in five patients. In two patients, the affected hemidiaphragm had a regular, however minimal and asynchronous motion during respiration. Respiratory variability of both tumor and diaphragm motions was about 20% although patients were instructed to breath normally. The findings showed significant differences compared to breathing patterns of patients without diaphragm dysfunction.

Conclusion

4D-MRI is a promising tool to analyze complex breathing patterns in patients with lung tumors. It should be considered for use in planning of radiotherapy to account for individual tumor motion.     

基于4DCT的腹部器官呼吸运动分析

背景与目的：个体化准确测量器官的呼吸移动度是确定腹部肿瘤体内边界（internal margin,IM）的前提。本研究应用4DCT（four-dimensional computed tomograpy）测量腹部器官在三维方向的呼吸移动度,并进一步分析膈肌与各器官移动度的关系。方法：选择13例肝癌患者行4DCT扫描,其中5例患者合并腹主动脉旁淋巴结转移。在10个呼吸时相的CT图像中分别勾画不同的器官,包括肝脏、双肾、胰腺、脾及腹主动脉旁淋巴结。在4DCT中测量膈肌及腹部各器官在三维方向的呼吸移动度,并分析膈肌移动度与各器官移动度是否相关。结果：膈肌在头尾方向的移动度为（10.3±4．0）mm,个体差异明显。肝、左右肾脏、胰腺、脾、腹主动脉旁淋巴结在头尾方向的移动度分别为（10．1±3．9）mm、（9．3±2．9）mm、（9．6±4．1）mm、（7．6±3．0）mm、（10．6±3．3）mm、（5．7±1．8）mm。肝脏、右肾的移动度与膈肌移动度无明显差异,且呈高度线性正相关关系;左肾、胰腺、脾的移动度与膈肌动度无明显相关;双侧肾脏的移动度相仿,但一侧肾脏的运动度并不能预测对侧肾脏的运动度。结论：应用4DCT可准确测量腹部器官在三维各方向的呼吸运动度。膈肌移动度可以代表肝脏和右肾头尾方向的运动度。而腹主动脉旁淋巴结的移动度相对较小。     

Four-dimensional measurement of intrafractional respiratory motion of pancreatic tumors using a 256 multi-slice CT scanner

Purpose

To quantify pancreas and pancreatic tumor movement due to respiratory motion using volumetric cine CT images.

Materials and methods

Six patients with pancreatic tumors were scanned in cine mode with a 256 multi-slice CT scanner under free breathing conditions. Gross tumor volume (GTV) and pancreas were manually contoured on the CT data set by a radiation oncologist. Intrafractional respiratory movement of the GTV and pancreas was calculated, and the results were compared between the respiratory ungated and gated phases, which is a 30% duty cycle around exhalation.

Results

Respiratory-induced organ motion was observed mainly in the anterior abdominal side than the posterior side. Average GTV displacement (ungated/gated phases) was 0.7 mm/0.2 mm in both the left and right directions, and 2.5 mm/0.9 mm in the anterior, 0.1 mm/0 mm in the posterior, and 8.9 mm/2.6 mm in the inferior directions. Average pancreas center of mass displacement relative to that at peak exhalation was mainly in the inferior direction, at 9.6 mm in the ungated phase and 2.3 mm in the gated phase.

Conclusions

By allowing accurate determination of the margin, quantitative analysis of tumor and pancreas displacement provides useful information in treatment planning in all radiation approaches for pancreatic tumors.     

CT scanning for radiation therapy treatment planning of hepatoma

One hundred forty-five patients with hepatoma had CT scanning for radiation therapy treatment planning. In order to demonstrate the anatomical distortions that occur with hepatoma and its effect on treatment planning, a control group of 50 colorectal cancer patients with normal livers was analyzed for comparison. The objectives of planning were to deliver as homogeneous a dose to the whole liver as possible and not to treat more than one of two functional kidneys or more than one-half of both functional kidneys. Conventional AP/PA portals were defined by physical examination, intravenous pyelogram, and bowel gas patterns at simulation and were found to be inadequate for the treatment of 76% of patients with hepatoma and 10% of patients with normal livers. Among the control group patients with no hepatoma, only 10% required oblique portals and 6% could not be treated because of left hydronephrosis or a solitary right kidney. Because the distortion of the liver in hepatoma in relationship to the kidneys required portal modification in 76% of hepatoma cases; 39% required oblique planning, 24% AP/PA, 20% PA and left lateral portals, and 17% required 4-field, 3-field or other plans in order to meet the treatment planning objectives. We concluded that all patients receiving radiation therapy to the liver for hepatoma require CT scanning for optimum radiation therapy treatment planning because of the hepatic distortion that occurs in hepatoma and the requirements of renal tolerance.     

Four-dimensional image-based treatment planning: Target volume segmentation and dose calculation in the presence of respiratory motion

PURPOSE: To describe approaches to four-dimensional (4D) treatment planning, including acquisition of 4D-CT scans, target delineation of spatio-temporal image data sets, 4D dose calculations, and their analysis. METHODS AND MATERIALS: The study included patients with thoracic and hepatocellular tumors. Specialized tools were developed to facilitate visualization, segmentation, and analysis of 4D-CT data: maximum intensity volume to define the extent of lung tumor motion, a 4D browser to examine and dynamically assess the 4D data sets, dose calculations, including respiratory motion, and deformable registration to combine the dose distributions at different points. RESULTS: Four-dimensional CT was used to visualize and quantitatively assess respiratory target motion. The gross target volume contours derived from light breathing scans showed significant differences compared with those extracted from 4D-CT. Evaluation of deformable registration using difference images of original and deformed anatomic maps suggested the algorithm is functionally useful. Thus, calculation of effective dose distributions, including respiratory motion, was implemented. CONCLUSION: Tools and methods to use 4D-CT data for treatment planning in the presence of respiratory motion have been developed and applied to several case studies. The process of 4D-CT-based treatment planning has been implemented, and technical barriers for its routine use have been identified.     

Maximum-intensity volumes for fast contouring of lung tumors including respiratory motion in 4DCT planning

PURPOSE: To assess the accuracy of maximum-intensity volumes (MIV) for fast contouring of lung tumors including respiratory motion. METHODS AND MATERIALS: Four-dimensional computed tomography (4DCT) data of 10 patients were acquired. Maximum-intensity volumes were constructed by assigning the maximum Hounsfield unit in all CT volumes per geometric voxel to a new, synthetic volume. Gross tumor volumes (GTVs) were contoured on all CT volumes, and their union was constructed. The GTV with all its respiratory motion was contoured on the MIV as well. Union GTVs and GTVs including motion were compared visually. Furthermore, planning target volumes (PTVs) were constructed for the union of GTVs and the GTV on MIV. These PTVs were compared by centroid position, volume, geometric extent, and surface distance. RESULTS: Visual comparison of GTVs demonstrated failure of the MIV technique for 5 of 10 patients. For adequate GTV(MIV)s, differences between PTVs were <1.0 mm in centroid position, 5% in volume, +/-5 mm in geometric extent, and +/-0.5 +/- 2.0 mm in surface distance. These values represent the uncertainties for successful MIV contouring. CONCLUSION: Maximum-intensity volumes are a good first estimate for target volume definition including respiratory motion. However, it seems mandatory to validate each individual MIV by overlaying it on a movie loop displaying the 4DCT data and editing it for possible inadequate coverage of GTVs on additional 4DCT motion states.     

Estimation of radiation-induced cancer from three-dimensional dose distributions: Concept of organ equivalent dose

PURPOSE: Estimates of secondary cancer risk after radiotherapy are becoming more important for comparative treatment planning. Modern treatment planning systems provide accurate three-dimensional dose distributions for each individual patient. These data open up new possibilities for more precise estimates of secondary cancer incidence rates in the irradiated organs. We report a new method to estimate organ-specific radiation-induced cancer incidence rates. The concept of an organ equivalent dose (OED) for radiation-induced cancer assumes that any two dose distributions in an organ are equivalent if they cause the same radiation-induced cancer incidence. METHODS AND MATERIALS: The two operational parameters of the OED concept are the organ-specific cancer incidence rate at low doses, which is taken from the data of the atomic bomb survivors, and cell sterilization at higher doses. The effect of cell sterilization in various organs was estimated by analyzing the secondary cancer incidence data of patients with Hodgkin's disease who were treated with radiotherapy in between 1962 and 1993. The radiotherapy plans used at the time the patients had been treated were reconstructed on a fully segmented whole body CT scan. The dose distributions were calculated in individual organs for which cancer incidence data were available. The model parameter that described cell sterilization was obtained by analyzing the dose and cancer incidence rates for the individual organs. RESULTS: We found organ-specific cell radiosensitivities that varied from 0.017 for the mouth and pharynx up to 1.592 for the bladder. Using the two model parameters (organ-specific cancer incidence rate and the parameter characterizing cell sterilization), the OED concept can be applied to any three-dimensional dose distribution to analyze cancer incidence. CONCLUSION: We believe that the concept of OED presented in this investigation represents a first step in assessing the potential risk of secondary cancer induction after the clinical application of radiotherapy.     

Improving soft-tissue contrast in four-dimensional computed tomography images of liver cancer patients using a deformable image registration method

PURPOSE: To investigate a deformable image registration method to improve soft-tissue contrast in four-dimensional (4D) computed tomography (CT) images of the liver. METHODS AND MATERIALS: Ten patients with hepatocellular carcinoma underwent 4D CT scan for radiotherapy treatment planning on a positron emission tomography/CT scanner. Four-dimensional CT images were binned into 10 equispaced phases. The exhale phase served as the reference phase, and images from the other nine phases were coregistered to the reference phase image using an intensity-based, automatic deformable image registration method. Then the coregistered images were combined to create a single, high-quality reconstructed CT image at exhale phase as the new reference for target delineation. The extent of image quality enhancement was quantified relative to the original CT by calculating the signal-to-noise ratio and the contrast-to-noise ratio. RESULTS: The soft tissue image contrast was noticeably better after deformable image registration than in the original scans. Signal-to-noise ratios inside the liver region of interest increased for all patients by a factor of 3.0 (range, 2.3-3.7). The improvement in image quality was not linearly proportionate to the number of images averaged. Using only 6 phases can achieve at least 85% of the contrast enhancement that can be achieved using all 10 phases. We also found that contrast enhancement was inversely proportional to the original image quality (p = 0.006), and the contrast enhancement is attained with little loss of spatial resolution. CONCLUSIONS: This deformable image registration method is feasible to improve soft-tissue image quality in 4D CT images.     

The role of CT scanning in the radiotherapy planning of pelvic tumors

In order to assess the place of computed tomography (CT) in radiotherapy planning, the tumor volumes are localized both by conventional techniques and with CT scanning under conditions simulating the radiotherapy. A comparison between the two methods has been made in a group of 55 patients with tumors in the pelvis. CT scanning was found to be of such value in 64 % of the treatment series, in improving both the accuracy of localization of the target volume (48 % of the patients) and the calculation of the dose distribution (31 % of the patients) that its use is recommended during the radiotherapy planning of pelvic tumors.