4D-CT lung motion estimation with deformable registration: quantification of motion nonlinearity and hysteresis.

In this article, our goal is twofold. First, we propose and compare two methods which process deformable registration to estimate patient specific lung and tumor displacements and deformation during free breathing from four-dimensional computed tomography (4D-CT) data. Second, we propose techniques to quantify the physiological parameters of motion nonlinearity and hysteresis. A Fréchet distance-based criterion is introduced to measure the motion hysteresis. Experiments were conducted with 4D-CT data of five patients treated in radiotherapy for non-small cell lung cancer. The accuracy of deformation fields assessed against expert-selected landmarks was found to be within image voxel tolerance. The second method gave slightly better results in terms of accuracy and consistency, although the differences were not statistically significant between the two methods. Lung motion nonlinearity and hysteresis are patient specific, and vary across regions within the lung during respiration. For all patients, motion between end-exhale and end-inhale was well approximated with a straight line trajectory for the majority of lung points. Hysteresis was found to be globally correlated with trajectory length. The main limitation to the proposed method is that intensity-based deformable registration is dependent on image quality and image resolution. Another limitation is the absence of gold standard which makes the validation of the computed motion difficult. However, the proposed tools provide patient specific motion information which, in radiotherapy for example, can ease the definition of precise internal margins. In the future, the integration of physiological information from multiple patients could help to create a general lung atlas with different clinical applications.

Evaluation of deformable registration of patient lung 4DCT with subanatomical region segmentations.

Deformable registration is needed for a variety of tasks in establishing the voxel correspondence between respiratory phases. Most registration algorithms assume or imply that the deformation field is smooth and continuous everywhere. However, the lungs are contained within closed invaginated sacs called pleurae and are allowed to slide almost independently along the chest wall. This sliding motion is characterized by a discontinuous vector field, which cannot be generated using standard deformable registration methods. The authors have developed a registration method that can create discontinuous vector fields at the boundaries of anatomical subregions. Registration is performed independently on each subregion, with a boundary-matching penalty used to prevent gaps. This method was implemented and tested using both the B-spline and Demons registration algorithms in the Insight Segmentation and Registration Toolkit. The authors have validated this method on four patient 4DCT data sets for registration of the end-inhalation and end-exhalation volumes. Multiple experts identified homologous points in the lungs and along the ribs in the two respiratory phases. Statistical analyses of the mismatch of the homologous points before and after registration demonstrated improved overall accuracy for both algorithms.

A comparison framework for breathing motion estimation methods from 4-D imaging.

Motion estimation is an important issue in radiation therapy of moving organs. In particular, motion estimates from 4-D imaging can be used to compute the distribution of an absorbed dose during the therapeutic irradiation. We propose a strategy and criteria incorporating spatiotemporal information to evaluate the accuracy of model-based methods capturing breathing motion from 4-D CT images. This evaluation relies on the identification and tracking of landmarks on the 4-D CT images by medical experts. Three different experts selected more than 500 landmarks within 4-D CT images of lungs for three patients. Landmark tracking was performed at four instants of the expiration phase. Two metrics are proposed to evaluate the tracking performance of motion-estimation models. The first metric cumulates over the four instants the errors on landmark location. The second metric integrates the error over a time interval according to an a priori breathing model for the landmark spatiotemporal trajectory. This latter metric better takes into account the dynamics of the motion. A second aim of this paper is to estimate the impact of considering several phases of the respiratory cycle as compared to using only the extreme phases (end-inspiration and end-expiration). The accuracy of three motion estimation models (two image registration-based methods and a biomechanical method) is compared through the proposed metrics and statistical tools. This paper points out the interest of taking into account more frames for reliably tracking the respiratory motion.

Simulation of four-dimensional CT images from deformable registration between inhale and exhale breath-hold CT scans.

PURPOSE: We propose to simulate an artificial four-dimensional (4-D) CT image of the thorax during breathing. It is performed by deformable registration of two CT scans acquired at inhale and exhale breath-hold. MATERIALS AND METHODS: Breath-hold images were acquired with the ABC (Active Breathing Coordinator) system. Dense deformable registrations were performed. The method was a minimization of the sum of squared differences (SSD) using an approximated second-order gradient. Gaussian and linear-elastic vector field regularizations were compared. A new preprocessing step, called a priori lung density modification (APLDM), was proposed to take into account lung density changes due to inspiration. It consisted of modulating the lung densities in one image according to the densities in the other, in order to make them comparable. Simulated 4-D images were then built by vector field interpolation and image resampling of the two initial CT images. A variation in the lung density was taken into account to generate intermediate artificial CT images. The Jacobian of the deformation was used to compute voxel values in Hounsfield units. The accuracy of the deformable registration was assessed by the spatial correspondence of anatomic landmarks located by experts. RESULTS: APLDM produced statistically significantly better results than the reference method (registration without APLDM preprocessing). The mean (and standard deviation) of distances between automatically found landmark positions and landmarks set by experts were 2.7(1.1) mm with APLDM, and 6.3(3.8) mm without. Interexpert variability was 2.3(1.2) mm. The differences between Gaussian and linear elastic regularizations were not statistically significant. In the second experiment using 4-D images, the mean difference between automatic and manual landmark positions for intermediate CT images was 2.6(2.0) mm. CONCLUSION: The generation of 4-D CT images by deformable registration of inhale and exhale CT images is feasible. This can lower the dose needed for 4-D CT acquisitions or can help to correct 4-D acquisition artifacts. The 4-D CT model can be used to propagate contours, to compute a 4-D dose map, or to simulate CT acquisitions with an irregular breathing signal. It could serve as a basis for 4-D radiation therapy planning. Further work is needed to make the simulation more realistic by taking into account hysteresis and more complex voxel trajectories.

Nonrigid registration method to assess reproducibility of breath-holding with ABC in lung cancer.

PURPOSE: To study the interfraction reproducibility of breath-holding using active breath control (ABC), and to develop computerized tools to evaluate three-dimensional (3D) intrathoracic motion in each patient. METHODS AND MATERIALS: Since June 2002, 11 patients with non-small-cell lung cancer enrolled in a Phase II trial have undergone four CT scans: one during free-breathing (reference) and three using ABC. Patients left the room between breath-hold scans. The patient's breath was held at the same predefined phase of the breathing cycle (about 70% of the vital capacity) using the ABC device, then patients received 3D-conformal radiotherapy. Automated computerized tools for breath-hold CT scans were developed to analyze lung and tumor interfraction residual motions with 3D nonrigid registration. RESULTS: All patients but one were safely treated with ABC for 7 weeks. For 6 patients, the lung volume differences were <5%. The mean 3D displacement inside the lungs was between 2.3 mm (SD 1.4) and 4 mm (SD 3.3), and the gross tumor volume residual motion was 0.9 mm (SD 0.4) to 5.9 mm (SD 0.7). The residual motion was slightly greater in the inferior part of the lung than the superior. For 2 patients, we detected volume changes >300 cm(3) and displacements >10 mm, probably owing to atelectasia and emphysema. One patient was excluded, and two others had incomplete data sets. CONCLUSION: Breath-holding with ABC was effective in 6 patients, and discrepancies were clinically accountable in 2. The proposed 3D nonrigid registration method allows for personalized evaluation of breath-holding reproducibility with ABC. It will be used to adapt the patient-specific internal margins.