To evaluate the implications of differences between manually drawn contours and contours automatically generated by deformable image registration (DIR) for 4D treatment planning.
Material and Methods
In 12 lung cancer patients intensity-modulated radiotherapy (IMRT) planning was performed for both manual contours and automatically generated (“auto”) contours in mid and peak expiration of four-dimensional computed tomography scans with the manual contours in peak inspiration serving as the reference for the displacement vector fields. Manual and auto plans were analysed with respect to their coverage of the manual contours which were assumed to represent the anatomically correct volumes.
Auto contours were on average larger than manual contours by up to 9%. Objective scores, D2% and D98% of the PTV, homogeneity and conformity indices, and coverage of normal tissue structures (lungs, heart, esophagus, spinal cord) at defined dose levels were not significantly different between both plans (p=0.22–0.94). Differences were statistically insignificant for the generalized equivalent uniform dose of the PTV (p=0.19–0.94) and normal tissue complication probabilities for lung and esophagus (p=0.13–0.47). Dosimetric differences >2% or >1 Gy were more frequent in patients with auto/manual volume differences ≥10% (p=0.04).
The applied DIR algorithm produces clinically plausible auto contours in the majority of structures. At this stage clinical supervision of the auto contouring process is required and manual interventions may become necessary. Prior to routine use further investigations are required to particularly reduce imaging artifacts.
Deformable image registration; automatic contouring; lung cancer; intensity modulated radiotherapy
Patients undergoing radiotherapy will inevitably show anatomical changes during the course of treatment. These can be weight loss, tumour shrinkage, and organ motion or filling changes. For advanced and adaptive radiotherapy (ART) information about anatomical changes must be extracted from repeated images in order to be able to evaluate and manage these changes. Deformable image registration (DIR) is a tool that can be used to efficiently gather information about anatomical changes. The aim of the present study was to evaluate the performance of two DIR methods for automatic organ at risk (OAR) contour propagation. Datasets from ten gynaecological patients having repeated computed tomography (CT) and cone beam computed tomography (CBCT) scans were collected. Contours were delineated on the planning CT and on every repeated scan by an expert clinician. DIR using our in-house developed featurelet-based method and the iPlan® BrainLab treatment planning system software was performed with the planning CT as reference and a selection of repeated scans as the target dataset. The planning CT contours were deformed using the resulting deformation fields and compared to the manually defined contours. Dice's similarity coefficients (DSCs) were calculated for each fractional patient scan structure, comparing the volume overlap using DIR with that using rigid registration only. No significant improvement in volume overlap was found after DIR as compared with rigid registration, independent of which image modality or DIR method was used. DIR needs to be further improved in order to facilitate contour propagation in the pelvic region in ART approaches.
radiotherapy; registration; deformable; organ; adaptive radiotherapy
We propose a planning method to design true 4-dimensional (4D) intensity-modulated radiotherapy (IMRT) plans, called the t4Dplan method, in which the planning target volume (PTV) of the individual phases of the 4D computed tomography (CT) and the conventional PTV receive non-uniform doses but the cumulative dose to the PTV of each phase, computed using deformable image registration (DIR), are uniform. The non-uniform dose prescription for the conventional PTV was obtained by solving linear equations that required motion-convolved 4D dose to be uniform to the PTV for the end-exhalation phase (PTV50) and by constraining maximum inhomogeneity to 20%. A plug-in code to the treatment planning system was developed to perform the IMRT optimization based on this non-uniform PTV dose prescription. The 4D dose was obtained by summing the mapped doses from individual phases of the 4D CT using DIR. This 4D dose distribution was compared with that of the internal target volume (ITV) method. The robustness of the 4D plans over the course of radiotherapy was evaluated by computing the 4D dose distributions on repeat 4D CT datasets. Three patients with lung tumors were selected to demonstrate the advantages of the t4Dplan method compared with the commonly used ITV method. The 4D dose distribution using the t4Dplan method resulted in greater normal tissue sparing (such as lung, stomach, liver and heart) than did plans designed using the ITV method. The dose volume histograms of cumulative 4D doses to the PTV50, clinical target volume, lung, spinal cord, liver, and heart on the 4D repeat CTs for the two patients were similar to those for the 4D dose at the time of original planning.
4D CT; IMRT; treatment planning; respiratory motion; deform
The fusion of computed tomography and magnetic resonance images is a software-dependent processing technique that enables one to integrate and analyze preoperative images for planning complex musculoskeletal tumor resections. By integrating various imaging modalities into one imaging data set we may facilitate preoperative image analysis and planning of navigation computer-assisted bone tumor resection and reconstruction. We performed image fusion for computer-assisted tumor surgery in 13 consecutive patients, seven males and six females, with a mean age of 35.8 years (range, 6–80 years). Visual verification of fused images was accurate in all patients. The mean time for image fusion was 30.6 minutes (range, 8–80 minutes). After intraoperative registration, all tumor resections were performed as planned preoperatively under navigation image guidance. Resections achieved after navigation resection planning were validated by postoperative CT or resected specimens in seven patients. Histologic examination of all resected specimens showed tumor-free margins in patients with bone sarcoma. The fusion of computed tomography and magnetic resonance imaging has the potential to enhance computer-assisted bone tumor surgery. The fusion image, when combined with surgical navigation, helps surgeons reproduce a preoperative plan reliably and may offer substantial clinical benefits.
Level of Evidence: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.
Electronic supplementary material
The online version of this article (doi:10.1007/s11999-008-0374-5) contains supplementary material, which is available to authorized users.
Image processing turns out to be essential in the planning and verification of radiotherapy treatments. Before applying a radiotherapy treatment, a dosimetry planning must be performed. Usually, the planning is done by means of an X-ray volumetric analysis using computerized tomography, where the area to be radiated is marked out. During the treatment phase, it is necessary to place the patient under the particle accelerator exactly as considered in the dosimetry stage. Coarse alignment is achieved using fiduciary markers placed over the patient’s skin as external references. Later, fine alignment is provided by comparing a digitally reconstructed radiography (DRR) from the planning stage and a portal image captured by the accelerator in the treatment stage. The preprocessing of DRR and portal images, as well as the minimization of the non-shared information between both kinds of images, is mandatory for the correct operation of the image registration algorithm. With this purpose, mathematical morphology and image processing techniques have been used. The present work describes a fully automatic method to calculate more accurately the necessary displacement of the couch to place the patient exactly at the planned position. The proposed method to achieve the correct positioning of the patient is based on advanced image registration techniques. Preliminary results show a perfect match with the displacement estimated by the physician.
Radiotherapy; Image registration; Image feature enhancement; Biomedical image analysis
Radiotherapy in Hodgkin’s Lymphoma (HL) is currently evolving with new attempts to further reduce radiation volumes to the involved-node concept (Involved Nodes Radiation Therapy, INRT) and with the use of intensity modulated radiotherapy (IMRT). Currently, IMRT can be planned and delivered with several techniques, and its role is not completely clear. We designed a planning study on a typical dataset drawn from clinical routine with the aim of comparing different IMRT solutions in terms of plan quality and treatment delivery efficiency.
A total of 10 young female patients affected with early stage mediastinal HL and treated with 30 Gy INRT after ABVD-based chemotherapy were selected from our database. Five different treatment techniques were compared: 3D-CRT, VMAT (single arc), B-VMAT (“butterfly”, multiple arcs), Helical Tomotherapy (HT) and Tomodirect (TD). Beam energy was 6 MV, and all IMRT planning solutions were optimized by inverse planning with specific dose-volume constraints on OAR (breasts, lungs, thyroid gland, coronary ostia, heart). Dose-Volume Histograms (DVHs) and Conformity Number (CN) were calculated and then compared, both for target and OAR by a statistical analysis (Wilcoxon’s Test).
PTV coverage was reached for all plans (V95% ≥ 95%); highest mean CN were obtained with HT (0.77) and VMAT (0.76). B-VMAT showed intermediate CN mean values (0.67), while the lowest CN were obtained with TD (0.30) and 3D-CRT techniques (0.30). A trend of inverse correlation between higher CN and larger healthy tissues volumes receiving low radiation doses was shown for lungs and breasts. For thyroid gland and heart/coronary ostia, HT, VMAT and B-VMAT techniques allowed a better sparing in terms of both Dmean and volumes receiving intermediate-high doses compared to 3D-CRT and TD.
IMRT techniques showed superior target coverage and OAR sparing, with, as an expected consequence, larger volumes of healthy tissues (lungs, breasts) receiving low doses. Among the different IMRT techniques, HT and VMAT showed higher levels of conformation; B-VMAT and HT emerged as the planning solutions able to achieve the most balanced compromise between higher conformation around the target and smaller volumes of OAR exposed to lower doses (typical of 3D-CRT).
Calculation of accumulated dose in fractionated radiotherapy based on spatial mapping of the dose points generally requires deformable image registration (DIR). The accuracy of the accumulated dose thus depends heavily on the DIR quality. This motivates investigations of how the registration uncertainty influences dose planning objectives and treatment outcome predictions.
A framework was developed where the dose mapping can be associated with a variable known uncertainty to simulate the DIR uncertainties in a clinical workflow. The framework enabled us to study the dependence of dose planning metrics, and the predicted treatment outcome, on the DIR uncertainty. The additional planning margin needed to compensate for the dose mapping uncertainties can also be determined. We applied the simulation framework to a hypofractionated proton treatment of the prostate using two different scanning beam spot sizes to also study the dose mapping sensitivity to penumbra widths.
The planning parameter most sensitive to the DIR uncertainty was found to be the target D95. We found that the registration mean absolute error needs to be ≤0.20 cm to obtain an uncertainty better than 3% of the calculated D95 for intermediate sized penumbras. Use of larger margins in constructing PTV from CTV relaxed the registration uncertainty requirements to the cost of increased dose burdens to the surrounding organs at risk.
The DIR uncertainty requirements should be considered in an adaptive radiotherapy workflow since this uncertainty can have significant impact on the accumulated dose. The simulation framework enabled quantification of the accuracy requirement for DIR algorithms to provide satisfactory clinical accuracy in the accumulated dose.
Radiotherapy; Adaptive radiotherapy; Dose tracking; Dose mapping; Dose accumulation; Dose accumulation accuracy; Deformable image registration; Non-rigid image registration; Protons
The cone-beam computed tomography (CBCT) imaging modality is an integral component of image-guided adaptive radiation therapy (IGART), which uses patient-specific dynamic/temporal information for potential treatment plan modification. In this study, an offline process for the integral component IGART framework has been implemented that consists of deformable image registration (DIR) and its validation, dose reconstruction, dose accumulation and dose verification. This study compares the differences between planned and estimated delivered doses under an IGART framework of five patients undergoing prostate cancer radiation therapy. The dose calculation accuracy on CBCT was verified by measurements made in a Rando pelvic phantom. The accuracy of DIR on patient image sets was evaluated in three ways: landmark matching with fiducial markers, visual image evaluation and unbalanced energy (UE); UE has been previously demonstrated to be a feasible method for the validation of DIR accuracy at a voxel level. The dose calculated on each CBCT image set was reconstructed and accumulated over all fractions to reflect the ‘actual dose’ delivered to the patient. The deformably accumulated (delivered) plans were then compared to the original (static) plans to evaluate tumor and normal tissue dose discrepancies. The results support the utility of adaptive planning, which can be used to fully elucidate the dosimetric impact based on the simulated delivered dose to achieve the desired tumor control and normal tissue sparing, which may be of particular importance in the context of hypofractionated radiotherapy regimens.
The purpose of this study was to demonstrate how magnetic resonance imaging (MRI) patient position protocols influence registration quality in patients with oropharyngeal cancer undergoing radical radiotherapy and the consequences for gross tumour volume (GTV) definition and radiotherapy planning.
Methods and materials
Twenty-two oropharyngeal patients underwent a computed tomography (CT), a diagnostic MRI (MRID) and an MRI in the radiotherapy position within an immobilization mask (MRIRT). Clinicians delineated the GTV on the CT viewing the MRID separately (GTVC); on the CT registered to MRID (GTVD) and on the CT registered to MRIRT (GTVRT). Planning target volumes (PTVs) were denoted similarly. Registration quality was assessed by measuring disparity between structures in the three set-ups. Volumetric modulated arc therapy (VMAT) radiotherapy planning was performed for PTVC, PTVD and PTVRT. To determine the dose received by the reference PTVRT, we optimized for PTVC and PTVD while calculating the dose to PTVRT. Statistical significance was determined using the two-tailed Mann–Whitney or two-tailed paired student t-tests.
A significant improvement in registration accuracy was found between CT and MRIRT versus the MRID measuring distances from the centre of structures (geometric mean error of 2.2 mm versus 6.6 mm). The mean GTVC (44.1 cm3) was significantly larger than GTVD (33.7 cm3, p value = 0.027) or GTVRT (30.5 cm3, p value = 0.014). When optimizing the VMAT plans for PTVC and investigating the mean dose to PTVRT neither the dose to 99% (58.8%) nor 95% of the PTV (84.7%) were found to meet the required clinical dose constraints of 90% and 95% respectively. Similarly, when optimizing for PTVD the mean dose to PTVRT did not meet clinical dose constraints for 99% (14.9%) nor 95% of the PTV (66.2%). Only by optimizing for PTVRT were all clinical dose constraints achieved.
When oropharyngeal patients MRI scans are performed in the radiotherapy position there are significant improvements in CT-MR image registration, target definition and PTV dose coverage.
MRI; CT; Oropharyngeal; Radiotherapy; Image registration; Patient setup
A constrained non-rigid registration (CNRR) algorithm for use in prostate image-guided adaptive radiotherapy is presented in a coherent mathematical framework. The registration algorithm is based on a global rigid transformation combined with a series of local injective non-rigid multi-resolution cubic B-spline Free Form Deformation (FFD) transformations. The control points of the FFD are used to non-rigidly constrain the transformation to the prostate, rectum, and bladder. As well, the control points are used to rigidly constrain the transformation to the estimated position of the pelvis, left femur, and right femur. The algorithm was tested with both 3D conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT) dose plan data sets. The 3DCRT dose plan set consisted of 10 fan-beam CT (FBCT) treatment-day images acquired from four different patients. The IMRT dose plan set consisted of 32 cone-beam CT (CBCT) treatment-day images acquired from 4 different patients. The CNRR was tested with different combinations of anatomical constraints and each test significantly outperformed both rigid and non-rigid registration at aligning constrained bones and critical organs. The CNRR results were used to adapt the dose plans to account for patient positioning errors as well as inter-day bone motion and intrinsic organ deformation. Each adapted dose plan improved performance by lowering radiation distribution to the rectum and bladder while increasing or maintaining radiation distribution to the prostate.
Non-rigid image registration; B-spline free form deformation; Rigid registration; Image-guided radiotherapy; Adaptive prostate radiotherapy
To evaluate the performance of surface-based deformable image registration (DR) for adaptive radiotherapy of non-small cell lung cancer (NSCLC).
Based on 13 patients with locally advanced NSCLC, CT images acquired at treatment planning, midway and the end of the radio- (n = 1) or radiochemotherapy (n = 12) course were used for evaluation of DR. All CT images were manually [gross tumor volume (GTV)] and automatically [organs-at-risk (OAR) lung, spinal cord, vertebral spine, trachea, aorta, outline] segmented. Contours were transformed into 3D meshes using the Pinnacle treatment planning system and corresponding mesh points defined control points for DR with interpolation within the structures. Using these deformation maps, follow-up CT images were transformed into the planning images and compared with the original planning CT images.
A progressive tumor shrinkage was observed with median GTV volumes of 170 cm3 (range 42 cm3 - 353 cm3), 124 cm3 (19 cm3 - 325 cm3) and 100 cm3 (10 cm3 - 270 cm3) at treatment planning, mid-way and at the end of treatment. Without DR, correlation coefficients (CC) were 0.76 ± 0.11 and 0.74 ± 0.10 for comparison of the planning CT and the CT images acquired mid-way and at the end of treatment, respectively; DR significantly improved the CC to 0.88 ± 0.03 and 0.86 ± 0.05 (p = 0.001), respectively. With manual landmark registration as reference, DR reduced uncertainties on the GTV surface from 11.8 mm ± 5.1 mm to 2.9 mm ± 1.2 mm. Regarding the carina and intrapulmonary vessel bifurcations, DR reduced uncertainties by about 40% with residual errors of 4 mm to 6 mm on average. Severe deformation artefacts were observed in patients with resolving atelectasis and pleural effusion, in one patient, where the tumor was located around large bronchi and separate segmentation of the GTV and OARs was not possible, and in one patient, where no clear shrinkage but more a decay of the tumor was observed.
The surface-based DR performed accurately for the majority of the patients with locally advanced NSCLC. However, morphological response patterns were identified, where results of the surface-based DR are uncertain.
Biological brain tumor imaging using O-(2-[18F]fluoroethyl)-L-tyrosine (FET)-PET combined with inverse treatment planning for locally restricted dose escalation in patients with glioblastoma multiforme seems to be a promising approach.
The aim of this study was to compare inverse with forward treatment planning for an integrated boost dose application in patients suffering from a glioblastoma multiforme, while biological target volumes are based on FET-PET and MRI data sets.
In 16 glioblastoma patients an intensity-modulated radiotherapy technique comprising an integrated boost (IB-IMRT) and a 3-dimensional conventional radiotherapy (3D-CRT) technique were generated for dosimetric comparison. FET-PET, MRI and treatment planning CT (P-CT) were co-registrated. The integrated boost volume (PTV1) was auto-contoured using a cut-off tumor-to-brain ratio (TBR) of ≥ 1.6 from FET-PET. PTV2 delineation was MRI-based. The total dose was prescribed to 72 and 60 Gy for PTV1 and PTV2, using daily fractions of 2.4 and 2 Gy.
After auto-contouring of PTV1 a marked target shape complexity had an impact on the dosimetric outcome. Patients with 3-4 PTV1 subvolumes vs. a single volume revealed a significant decrease in mean dose (67.7 vs. 70.6 Gy). From convex to complex shaped PTV1 mean doses decreased from 71.3 Gy to 67.7 Gy. The homogeneity and conformity for PTV1 and PTV2 was significantly improved with IB-IMRT. With the use of IB-IMRT the minimum dose within PTV1 (61.1 vs. 57.4 Gy) and PTV2 (51.4 vs. 40.9 Gy) increased significantly, and the mean EUD for PTV2 was improved (59.9 vs. 55.3 Gy, p < 0.01). The EUD for PTV1 was only slightly improved (68.3 vs. 67.3 Gy). The EUD for the brain was equal with both planning techniques.
In the presented planning study the integrated boost concept based on inversely planned IB-IMRT is feasible. The FET-PET-based automatically contoured PTV1 can lead to very complex geometric configurations, limiting the achievable mean dose in the boost volume. With IB-IMRT a better homogeneity and conformity, compared to 3D-CRT, could be achieved.
The long-term dose-effect relationship for specific cardiac structures in mediastinal radiotherapy has rarely been investigated. As part of an interdisciplinary project, the 3-D dose distribution within the heart was reconstructed in all long-term Hodgkin's disease survivors (n = 55) treated with mediastinal radiotherapy between 1978 and 1985. For dose reconstruction, original techniques were transferred to the CT data sets of appropriate test patients, in whom left (LV) and right ventricle (RV), left (LA) and right atrium (RA) as well as right (RCA), left anterior descending (LAD) and left circumflex (LCX) coronary arteries were contoured. Dose-volume histograms (DVHs) were generated for these heart structures and results compared between techniques.
Predominant technique was an anterior mantle field (cobalt-60). 26 patients (47%) were treated with anterior mantle field alone (MF), 18 (33%) with anterior mantle field and monoaxial, bisegmental rotation boost (MF+ROT), 7 (13%) with anterior mantle field and dorsal boost (MF+DORS) and 4 (7%) with other techniques. Mean ± SD total mediastinal doses for MF+ROT (41.7 ± 3.5 Gy) and for MF+DORS (42.7 ± 7.4) were significantly higher than for MF (36.7 ± 5.2 Gy). DVH analysis documented relative overdosage to right heart structures with MF (median maximal dose to RV 129%, to RCA 127%) which was siginificantly reduced to 117% and 112%, respectively, in MF+ROT. Absolute doses in right heart structures, however, did not differ between techniques. Absolute LA doses were significantly higher in MF+ROT patients than in MF patients where large parts of LA were blocked. Median maximal doses for all techniques ranged between 48 and 52 Gy (RV), 44 and 46 Gy (LV), 47 and 49 Gy (RA), 38 and 45 Gy (LA), 46 and 50 Gy (RCA), 39 and 44 Gy (LAD) and 34 and 42 Gy (LCX).
In patients irradiated with anterior mantle-field techniques, high doses to anterior heart portions were partly compensated by boost treatment from non-anterior angles. As the threshold doses for coronary artery disease, cardiomyopathy, pericarditis and valvular changes are assumed to be 30 to 40 Gy, cardiac toxicity must be anticipated in these patients. Thus, dose distributions in individual subjects should be correlated to the corresponding cardiovascular findings in these long-term survivors, e. g. by cardiovascular magnetic resonance imaging.
To investigate the effect of breathing motion and dose accumulation on the planned radiotherapy dose to liver tumors and normal tissues using deformable image registration.
Method and Materials
Twenty one free-breathing stereotactic liver cancer radiotherapy patients, planned on static exhale CT for 27 – 60 Gy in 6 fractions, were included. A biomechanical model-based deformable image registration algorithm, retrospectively deformed each exhale CT to inhale CT. This deformation map was combined with exhale and inhale dose grids from the treatment planning system to accumulate dose over the breathing cycle. Accumulation was also investigated using a simple rigid liver-to-liver registration. Changes to tumor and normal tissue dose were quantified.
Relative to static plans, mean dose change (range) after deformable dose accumulation (as % of prescription dose) was −1 (−14, 8) to minimum tumor, −4 (−15, 0) to max bowel, −4 (−25, 1) to max duodenum, 2 (−1, 9) to max esophagus, −2 (−13, 4) to max stomach, 0 (−3, 4) to mean liver, and −1 (−5, 1) and −2 (−7, 1) to mean left and right kidneys. Compared to deformable registration, rigid modeling had changes up to 8% to minimum tumor and 7% to maximum normal tissues.
Deformable registration and dose accumulation revealed potentially significant dose changes to either a tumor or normal tissue in the majority of cases due to breathing motion. These changes may not be accurately accounted for with rigid motion.
Deformable image registration; respiratory motion; 4D dose calculations; stereotactic body radiotherapy; liver cancer
To demonstrate the feasibility of registering hyperpolarized helium-3 magnetic resonance images (3He-MRI) to X-ray computed tomography (CT) for functionally weighted intensity-modulated radiotherapy (IMRT) planning.
Methods and Materials
Six patients with non-small-cell lung cancer underwent 3He ventilation MRI, which was fused with radiotherapy planning CT using rigid registration. Registration accuracy was assessed using an overlap coefficient, calculated as the proportion of the segmented 3He-MR volume (VMRI) that intersects the segmented CT lung volume expressed as a percentage of VMRI. For each patient, an IMRT plan that minimized the volume of total lung receiving a dose ≥20 Gy (V20) was compared with a plan that minimized the V20 to well-ventilated lung defined by the registered 3He-MRI.
The 3He-MRI and CT were registered with sufficient accuracy to enable functionally guided IMRT planning (median overlap, 89%; range, 72-97%). In comparison with the total lung IMRT plans, IMRT constrained with 3He-MRI reduced the V20 not only for the well-ventilated lung (median reduction, 3.1%; range, 0.4-5.1%; p = 0.028) but also for the total lung volume (median reduction, 1.6%; range, 0.2-3.7%; p = 0.028).
Statistically significant improvements to IMRT plans are possible using functional information provided by 3He-MRI that has been registered to radiotherapy planning CT.
Hyperpolarized helium-3 MRI; Image registration; IMRT treatment planning; Non-small-cell lung cancer
Purpose: To demonstrate the feasibility of registering hyperpolarized helium-3 magnetic resonance images (3He-MRI) to X-ray computed tomography (CT) for functionally weighted intensity-modulated radiotherapy (IMRT) planning.
Methods and Materials: Six patients with non–small-cell lung cancer underwent 3He ventilation MRI, which was fused with radiotherapy planning CT using rigid registration. Registration accuracy was assessed using an overlap coefficient, calculated as the proportion of the segmented 3He-MR volume (VMRI) that intersects the segmented CT lung volume expressed as a percentage of VMRI. For each patient, an IMRT plan that minimized the volume of total lung receiving a dose ≥20 Gy (V20) was compared with a plan that minimized the V20 to well-ventilated lung defined by the registered 3He-MRI.
Results: The 3He-MRI and CT were registered with sufficient accuracy to enable functionally guided IMRT planning (median overlap, 89%; range, 72–97%). In comparison with the total lung IMRT plans, IMRT constrained with 3He-MRI reduced the V20 not only for the well-ventilated lung (median reduction, 3.1%; range, 0.4–5.1%; p = 0.028) but also for the total lung volume (median reduction, 1.6%; range, 0.2–3.7%; p = 0.028).
Conclusions: Statistically significant improvements to IMRT plans are possible using functional information provided by 3He-MRI that has been registered to radiotherapy planning CT.
Hyperpolarized helium-3 MRI; Image registration; IMRT treatment planning; Non–small-cell lung cancer
The purpose of this proof-of-principle study was to test the ability of an intensity-modulated radiotherapy (IMRT) technique to reduce the radiation dose to the heart plus the left ventricle and a coronary artery. Radiation-induced heart disease might be a serious complication in long-term cancer survivors.
Planning CT scans from 6 female patients were available. They were part of a previous study of mediastinal IMRT for target volumes used in lymphoma treatment that included 8 patients and represent all cases where the left anterior descending coronary artery (LAD) could be contoured. We compared 6 MV AP/PA opposed fields to a 3D conformal 4-field technique and an optimised 7-field step-and-shoot IMRT technique and evaluated DVH's for several structures. The planning system was BrainSCAN 5.21 (BrainLAB, Heimstetten, Germany).
IMRT maintained target volume coverage but resulted in better dose reduction to the heart, left ventricle and LAD than the other techniques. Selective dose reduction could be accomplished, although not to the degree initially attempted. The median LAD dose was approximately 50% lower with IMRT. In 5 out of 6 patients, IMRT was the best technique with regard to heart sparing.
IMRT techniques are able to reduce the radiation dose to the heart. In addition to dose reduction to whole heart, individualised dose distributions can be created, which spare, e.g., one ventricle plus one of the coronary arteries. Certain patients with well-defined vessel pathology might profit from an approach of general heart sparing with further selective dose reduction, accounting for the individual aspects of pre-existing damage.
In prostate brachytherapy, determining the 3D location of the seeds relative to surrounding structures is necessary for calculating dosimetry. Ultrasound imaging provides the ability to visualize soft tissues, and implanted seeds can be reconstructed from C-arm fluoroscopy. Registration between these two complementary modalities would allow us to make immediate provisions for dosimetric deviation from the optimal implant plan.
We propose intensity-based registration between ultrasound and a reconstructed model of seeds from fluoroscopy. The ultrasound images are pre-processed with recursive thresholding and phase congruency. Then a 3D ultrasound volume is reconstructed and registered to the implant model using mutual information.
A standard training phantom was implanted with 49 seeds. Average registration error between corresponding seeds relative to the ground truth is 0.09 mm. The effect of false positives in ultrasound was investigated by masking seeds from the fluoroscopy reconstructed model. The registration error remained below 0.5 mm at a rate of 30% false positives.
Our method promises to be clinically adequate, where requirements for registration is 1.5 mm.
Prostate brachytherapy; Ultrasound; Fluoroscopy; Registration
Cure rate of early Hodgkin Lymphoma are high and avoidance of late toxicities is of paramount importance. This comparative study aims to assess the normal tissue sparing capability of intensity-modulated radiation therapy (IMRT) versus standard three-dimensional conformal radiotherapy (3D-CRT) in terms of dose-volume parameters and normal tissue complication probability (NTCP) for different organs at risk in supradiaphragmatic Hodgkin Lymphoma (HL) patients.
Ten HL patients were actually treated with 3D-CRT and all treatments were then re-planned with IMRT. Dose-volume parameters for thyroid, oesophagus, heart, coronary arteries, lung, spinal cord and breast were evaluated. Dose-volume histograms generated by TPS were analyzed to predict the NTCP for the considered organs at risk, according to different endpoints.
Regarding dose-volume parameters no statistically significant differences were recorded for heart and origin of coronary arteries. We recorded statistically significant lower V30 with IMRT for oesophagus (6.42 vs 0.33, p = 0.02) and lungs (4.7 vs 0.1 p = 0.014 for the left lung and 2.59 vs 0.1 p = 0.017 for the right lung) and lower V20 for spinal cord (17.8 vs 7.2 p = 0.02). Moreover the maximum dose to the spinal cord was lower with IMRT (30.2 vs 19.9, p <0.001). Higher V10 with IMRT for thyroid (64.8 vs 95, p = 0.0019) and V5 for lungs (30.3 vs 44.8, p = 0.03, for right lung and 28.9 vs 48.1, p = 0.001 for left lung) were found, respectively. Higher V5 and V10 for breasts were found with IMRT (V5: 4.14 vs 20.6, p = 0.018 for left breast and 3.3 vs 17, p = 0.059 for right breast; V10: 2.5 vs 13.6 p = 0.035 for left breast and 1.7 vs 11, p = 0.07 for the right breast.) As for the NTCP, our data point out that IMRT is not always likely to significantly increase the NTCP to OARs.
In HL male patients IMRT seems feasible and accurate while for women HL patients IMRT should be used with caution.
Hodgkin; IMRT; 3D-CRT; NTCP
To evaluate the utility of the preoperative PET-CT using deformable image registration (DIR) in the treatment of patients with locally advanced breast cancer and to find appropriate radiotherapy technique for further adequate treatment of axillary nodal area.
Sixty-five breast cancer patients who had level II, III axillary or supraclavicular lymph node metastasis on 18F-FDG PET-CT and received postoperative radiotherapy after modified radical mastectomy were enrolled. One radiation oncologist contoured normal organs (axillary vessels, clavicular head, coracoids process and humeral head) and involved lymph nodes on PET-CT and simulation CT slices. After contouring, deformable image registration of PET-CT on simulation CT was carried out. To evaluate the performance of the DIR, Dice similarity coefficient (DSC) and Center of mass (COM) were used. We created two plans, one was the historically designed three field plan and the other was the modified plan based on the location of axillary lymph node, and we compared the doses that irradiated the axillary lymph nodes.
The DSCs for axillary artery, axillary vein, clavicular head, coracoids process and humeral head were 0.43 ± 0.15, 0.39 ± 0.20, 0.85 ± 0.10, 0.72 ± 0.20 and 0.77 ± 0.20, respectively. The distances between the COMs of axillary artery, axillary vein, clavicular head, coracoids process and humeral head in simulation CT and from PET-CT were 13.0 ±7.1, 20.2 ± 11.2, 4.4 ± 6.3, 3.7 ± 6.7, and 9.5 ± 25.0 mm, respectively. In the historically designed plan, only 57.7% of level II lymph nodes received more than 95% of prescribed dose and the coverage was improved to 70.0% with the modified plan (p < 0.01). For level III lymph nodes, the volumes received more than 95% of prescribed dose were similar in both plans (96.8 % vs 97.9%, p = 0.35).
Deformable image registration of PET-CT on simulation CT was helpful in the identification of the location of the preoperatively involved axillary lymph node. Historically designed three-field plan was not adequate to treat the axillary level II lymph node area. Novel treatment technique based on the location of axillary lymph node from PET-CT using DIR can result in more adequate coverage of nodal area.
Breast cancer; Deformable image registration (DIR); Radiotherapy; PET-CT
To investigate the utilization of PET-CT in target volume delineation for three-dimensional conformal radiotherapy in patients with non-small cell lung cancer (NSCLC) and atelectasis.
Thirty NSCLC patients who underwent radical radiotherapy from August 2010 to March 2012 were included in this study. All patients were pathologically confirmed to have atelectasis by imaging examination. PET-CT scanning was performed in these patients. According to the PET-CT scan results, the gross tumor volume (GTV) and organs at risk (OARs, including the lungs, heart, esophagus and spinal cord) were delineated separately both on CT and PET-CT images. The clinical target volume (CTV) was defined as the GTV plus a margin of 6-8 mm, and the planning target volume (PTV) as the GTV plus a margin of 10-15mm. An experienced physician was responsible for designing treatment plans PlanCT and PlanPET-CT on CT image sets. 95% of the PTV was encompassed by the 90% isodose curve, and the two treatment plans kept the same beam direction, beam number, gantry angle, and position of the multi-leaf collimator as much as possible. The GTV was compared using a target delineation system, and doses distributions to OARs were compared on the basis of dose-volume histogram (DVH) parameters.
The GTVCT and GTVPET-CT had varying degrees of change in all 30 patients, and the changes in the GTVCT and GTVPET-CT exceeded 25% in 12 (40%) patients. The GTVPET-CT decreased in varying degrees compared to the GTVCT in 22 patients. Their median GTVPET-CT and median GTVPET-CT were 111.4 cm3 (range, 37.8 cm3-188.7 cm3) and 155.1 cm3 (range, 76.2 cm3-301.0 cm3), respectively, and the former was 43.7 cm3 (28.2%) less than the latter. The GTVPET-CT increased in varying degrees compared to the GTVCT in 8 patients. Their median GTVPET-CT and median GTVPET-CT were 144.7 cm3 (range, 125.4 cm3-178.7 cm3) and 125.8 cm3 (range, 105.6 cm3-153.5 cm3), respectively, and the former was 18.9 cm3 (15.0%) greater than the latter. Compared to PlanCT parameters, PlanPET-CT parameters showed varying degrees of changes. The changes in lung V20, V30, esophageal V50 and V55 were statistically significant (Ps< 0.05 for all), while the differences in mean lung dose, lung V5, V10, V15, heart V30, mean esophageal dose, esophagus Dmax, and spinal cord Dmax were not significant (Ps> 0.05 for all).
PET-CT allows a better distinction between the collapsed lung tissue and tumor tissue, improving the accuracy of radiotherapy target delineation, and reducing radiation damage to the surrounding OARs in NSCLC patients with atelectasis.
Atelectasis; PET-CT; Non-small cell lung cancer; Target volume; Three-dimensional conformal radiotherapy
Head and neck radiotherapy planning with positron emission tomography/computed tomography (PET/CT) requires the images to be reliably registered with treatment planning CT. Acquiring PET/CT in treatment position is problematic, and in practice for some patients it may be beneficial to use diagnostic PET/CT for radiotherapy planning. Therefore, the aim of this study was first to quantify the image registration accuracy of PET/CT to radiotherapy CT and, second, to assess whether PET/CT acquired in diagnostic position can be registered to planning CT.
Methods and Materials
Positron emission tomography/CT acquired in diagnostic and treatment position for five patients with head and neck cancer was registered to radiotherapy planning CT using both rigid and nonrigid image registration. The root mean squared error for each method was calculated from a set of anatomic landmarks marked by four independent observers.
Nonrigid and rigid registration errors for treatment position PET/CT to planning CT were 2.77 ± 0.80 mm and 4.96 ± 2.38 mm, respectively, p = 0.001. Applying the nonrigid registration to diagnostic position PET/CT produced a more accurate match to the planning CT than rigid registration of treatment position PET/CT (3.20 ± 1.22 mm and 4.96 ± 2.38 mm, respectively, p = 0.012).
Nonrigid registration provides a more accurate registration of head and neck PET/CT to treatment planning CT than rigid registration. In addition, nonrigid registration of PET/CT acquired with patients in a standardized, diagnostic position can provide images registered to planning CT with greater accuracy than a rigid registration of PET/CT images acquired in treatment position. This may allow greater flexibility in the timing of PET/CT for head and neck cancer patients due to undergo radiotherapy.
Nonrigid image registration; PET; Radiotherapy treatment planning; Head and neck cancer
Purpose: Head and neck radiotherapy planning with positron emission tomography/computed tomography (PET/CT) requires the images to be reliably registered with treatment planning CT. Acquiring PET/CT in treatment position is problematic, and in practice for some patients it may be beneficial to use diagnostic PET/CT for radiotherapy planning. Therefore, the aim of this study was first to quantify the image registration accuracy of PET/CT to radiotherapy CT and, second, to assess whether PET/CT acquired in diagnostic position can be registered to planning CT.
Methods and Materials: Positron emission tomography/CT acquired in diagnostic and treatment position for five patients with head and neck cancer was registered to radiotherapy planning CT using both rigid and nonrigid image registration. The root mean squared error for each method was calculated from a set of anatomic landmarks marked by four independent observers.
Results: Nonrigid and rigid registration errors for treatment position PET/CT to planning CT were 2.77 ± 0.80 mm and 4.96 ± 2.38 mm, respectively, p = 0.001. Applying the nonrigid registration to diagnostic position PET/CT produced a more accurate match to the planning CT than rigid registration of treatment position PET/CT (3.20 ± 1.22 mm and 4.96 ± 2.38 mm, respectively, p = 0.012).
Conclusions: Nonrigid registration provides a more accurate registration of head and neck PET/CT to treatment planning CT than rigid registration. In addition, nonrigid registration of PET/CT acquired with patients in a standardized, diagnostic position can provide images registered to planning CT with greater accuracy than a rigid registration of PET/CT images acquired in treatment position. This may allow greater flexibility in the timing of PET/CT for head and neck cancer patients due to undergo radiotherapy.
Nonrigid image registration; PET; Radiotherapy treatment planning; Head and neck cancer
Distension and shape of urinary bladder may vary during intracavitary brachytherapy (ICBT) for cervical cancer, significantly affecting doses to bladder, rectum, sigmoid colon and small intestine and consequently late radiation toxicities. This study is to evaluate the effects of different fixed volume bladder distention on dosimetry, assessed by three dimensional image based planning, in different organs at risk during the treatment of cervical cancer with ICBT.
Material and methods
Forty seven cervical cancer patients (stage IB to IVA) were qualified for ICBT following external beam radiotherapy. Urinary bladder was distended with different volumes of normal saline instilled by a Foley's catheter. Planning CT scans were performed after insertion of applicators and three dimensional treatment planning was done on Brachyvision® treatment planning system (Varian Medical Systems, Palo Alto, CA). Dose volume histograms were analyzed. Bladder, rectum, sigmoid colon and small intestine doses were collected for individual plans and compared, based on the amount of bladder filling.
Mean dose to the bladder significantly decreased with increased bladder filling. However, doses to the small volumes (0.1 cc, 1 cc, 2 cc) which are relevant for brachytherapy, did not change significantly with bladder filling for bladder, rectum or sigmoid colon. Nevertheless, all dose values of small intestine are decreased significantly with bladder filling.
Bladder distension has no significant effect on doses received during brachytherapy by relevant volumes of bladder, rectum and sigmoid colon except intestine where values are decreased with bladder distension. A larger study with clinical correlation of late toxicities is essential for proper evaluation of this strategy.
bladder distension; cervical cancer; dosimetric comparison; intracavitary brachytherapy
The FAST (FASTer radiotherapy for breast radiotherapy) trial
is a UK Phase 2 multicentre randomised clinical trial evaluating a five-fraction
schedule of whole-breast radiotherapy following local excision of early breast
cancer. The purpose of this quality assurance study was to analyse the radiotherapy
planning data in order to confirm compliance with the trial protocol.
915 patients were recruited between 2004 and 2007 from 18 centres. The
protocol required that all centres should use three-dimensional dose compensations
to optimise radiotherapy plans. Planning techniques, maximum dose (Dmax)
and dose–volume histograms from treatment plans were evaluated and compared
between centres. The homogeneity of plans was tested by creating a cut-off
value of 5% for the percentage of breast volume receiving >105%
of the prescribed dose.
672 data sets from 15 centres were available. 93% (624/672)
of plans were treated using forward-planned multileaf collimator (MLC)
segments, 6% with breast compensators and 1% with inverse-planned
MLC segments. 94% (635/672) of patients had a Dmax≤107%
of the prescribed dose. 11% (74/672) of plans delivered >105%
of the prescribed dose to >5% of the breast volume.
Reviewing the data in this study, 95% of plans submitted by centres
complied with the protocol. With the improved breast radiotherapy standards
shown in FAST centres, the following recommendations were suggested for future
UK breast radiotherapy trials: (i) the minimum, mean and maximum
dose to the whole-breast planning target volume (PTV) should be
recorded and assessed; (ii) apart from having a Dmax≤107%
of the prescribed dose, ≤5% of PTV should a receive dose >105%
of the prescription dose.