A multichannel feature-based approach for longitudinal lung CT registration in the presence of radiation induced lung damage

Quantifying parenchymal tissue changes in the lungs is imperative in furthering the study of radiation-induced lung damage (RILD). Registering lung images from different time-points is a key step of this process. Traditional intensity-based registration approaches fail this task due to the considerable anatomical changes that occur between timepoints. This work proposes a novel method to successfully register longitudinal pre- and post-radiotherapy (RT) lung CT scans that exhibit large changes due to RILD, by extracting consistent anatomical features from CT (lung boundaries, main airways, vessels) and using these features to optimise the registrations. Pre-RT and 12-month post-RT CT pairs from fifteen lung cancer patients were used for this study, all with varying degrees of RILD, ranging from mild parenchymal change to extensive consolidation and collapse. For each CT, signed distance transforms from segmentations of the lungs and main airways were generated, and the Frangi vesselness map was calculated. These were concatenated into multi-channel images and diffeomorphic multichannel registration was performed for each image pair using NiftyReg. Traditional intensity-based registrations were also performed for comparison purposes. For the evaluation, the pre- and post-registration landmark distance was calculated for all patients, using an average of 44 manually identified landmark pairs per patient. The mean (standard deviation) distance for all datasets decreased from 15.95 (8.09) mm pre-registration to 4.56 (5.70) mm post-registration, compared to 7.90 (8.97) mm for the intensity-based registrations. Qualitative improvements in image alignment were observed for all patient datasets. For four representative subjects, registrations were performed for 3 additional follow-up timepoints up to 48-months post-RT and similar accuracy was achieved. We have demonstrated that our novel multichannel registration method can successfully align longitudinal scans from RILD patients in the presence of large anatomical changes such as consolidation and atelectasis, outperforming the traditional registration approach both quantitatively and through thorough visual inspection

Investigation of the evolution of radiation-induced lung damage using serial CT imaging and pulmonary function tests

Background and purpose: Radiation-induced lung damage (RILD) is a common consequence of lung cancer radiotherapy (RT) with unclear evolution over time. We quantify radiological RILD longitudinally and correlate it with dosimetry and respiratory morbidity. Materials and methods: CTs were available pre-RT and at 3, 6, 12 and 24-months post-RT for forty-five subjects enrolled in a phase 1/2 clinical trial of isotoxic, dose-escalated chemoradiotherapy for locally advanced non-small cell lung cancer. Fifteen CT-based measures of parenchymal, pleural and lung volume change, and anatomical distortions, were calculated. Respiratory morbidity was assessed with the Medical Research Council (MRC) dyspnoea score and spirometric pulmonary function tests (PFTs): FVC, FEV1, FEV1/FVC and DLCO. Results: FEV1, FEV1/FVC and MRC scores progressively declined post-RT; FVC decreased by 6-months before partially recovering. Radiologically, an early phase (3–6 months) of acute inflammation was characterised by reversible parenchymal change and non-progressive anatomical distortion. A phase of chronic scarring followed (6–24 months) with irreversible parenchymal change, progressive volume loss and anatomical distortion. Post-RT increase in contralateral lung volume was common. Normal lung volume shrinkage correlated longitudinally with mean lung dose (r = 0.30–0.40, p = 0.01–0.04). Radiological findings allowed separation of patients with predominant acute versus chronic RILD; subjects with predominantly chronic RILD had poorer pre-RT lung function. Conclusions: CT-based measures enable detailed quantification of the longitudinal evolution of RILD. The majority of patients developed progressive lung damage, even when the early phase was absent or mild. Pre-RT lung function and RT dosimetry may allow to identify subjects at increased risk of RILD

Simulation of a new respiratory phase sorting method for 4D-imaging using optical surface information towards precision radiotherapy

Background: Respiratory signal detection is critical for 4-dimensional (4D) imaging. This study proposes and evaluates a novel phase sorting method using optical surface imaging (OSI), aiming to improve the precision of radiotherapy. Method: Based on 4D Extended Cardiac-Torso (XCAT) digital phantom, OSI in point cloud format was generated from the body segmentation, and image projections were simulated using the geometries of Varian 4D kV cone-beam-CT (CBCT). Respiratory signals were extracted respectively from the segmented diaphragm image (reference method) and OSI respectively, where Gaussian Mixture Model and Principal Component Analysis (PCA) were used for image registration and dimension reduction respectively. Breathing frequencies were compared using Fast-Fourier-Transform. Consistency of 4DCBCT images reconstructed using Maximum Likelihood Expectation Maximization algorithm was also evaluated quantitatively, where high consistency can be suggested by lower Root-Mean-Square-Error (RMSE), Structural-Similarity-Index (SSIM) value closer to 1, and larger Peak-Signal-To-Noise-Ratio (PSNR) respectively. Results: High consistency of breathing frequencies was observed between the diaphragm-based (0.232 Hz) and OSI-based (0.251 Hz) signals, with a slight discrepancy of 0.019Hz. Using end of expiration (EOE) and end of inspiration (EOI) phases as examples, the mean±1SD values of the 80 transverse, 100 coronal and 120 sagittal planes were 0.967, 0,972, 0.974 (SSIM); 1.657 ± 0.368, 1.464 ± 0.104, 1.479 ± 0.297 (RMSE); and 40.501 ± 1.737, 41.532 ± 1.464, 41.553 ± 1.910 (PSNR) for the EOE; and 0.969, 0.973, 0.973 (SSIM); 1.686 ± 0.278, 1.422 ± 0.089, 1.489 ± 0.238 (RMSE); and 40.535 ± 1.539, 41.605 ± 0.534, 41.401 ± 1.496 (PSNR) for EOI respectively. Conclusions: This work proposed and evaluated a novel respiratory phase sorting approach for 4D imaging using optical surface signals, which can potentially be applied to precision radiotherapy. Its potential advantages were non-ionizing, non-invasive, non-contact, and more compatible with various anatomic regions and treatment/imaging systems

Quantitative Analysis of Radiation-Associated Parenchymal Lung Change

We present a novel classification system of the parenchymal features of radiation-induced lung damage (RILD). We developed a deep learning network to automate the delineation of five classes of parenchymal textures. We quantify the volumetric change in classes after radiotherapy in order to allow detailed, quantitative descriptions of the evolution of lung parenchyma up to 24 months after RT, and correlate these with radiotherapy dose and respiratory outcomes. Diagnostic CTs were available pre-RT, and at 3, 6, 12 and 24 months post-RT, for 46 subjects enrolled in a clinical trial of chemoradiotherapy for non-small cell lung cancer. All 230 CT scans were segmented using our network. The five parenchymal classes showed distinct temporal patterns. Moderate correlation was seen between change in tissue class volume and clinical and dosimetric parameters, e.g., the Pearson correlation coefficient was ≤0.49 between V30 and change in Class 2, and was 0.39 between change in Class 1 and decline in FVC. The effect of the local dose on tissue class revealed a strong dose-dependent relationship. Respiratory function measured by spirometry and MRC dyspnoea scores after radiotherapy correlated with the measured radiological RILD. We demonstrate the potential of using our approach to analyse and understand the morphological and functional evolution of RILD in greater detail than previously possible

Supervoxel-based image registration and analysis with application to lung cancer

Lung diseases, including lung cancer, are amongst the largest burdens to healthcare systems worldwide. Improving the extraction of information from imaging data has the potential to provide more accurate diagnosis and more effective treatment. For example, assessing regional lung function could guide more effective radiotherapy treatment to spare well-functioning parts of the lungs. One meaningful regional representation is achieved by locally clustering similar image voxels together using the concept of supervoxels, which allows for bulk regional processing and analysis, whilst removing redundant information. This thesis aims to lay further foundations for supervoxel-based image analysis by presenting novel deformable lung image registration frameworks, as well as a method to estimate lung ventilation using supervoxels. We demonstrate how a supervoxel-based image representation can be combined with graph cuts as a discrete optimisation-based approach to provide effcient and accurate 3D deformable image registration. Our work overcomes some of the previous limitations by posing the problem on a graph created by adjacent supervoxels. We further show that the application of a relaxed graph representation of the image, followed by guided image filtering over the estimated deformation �field, allows us to model `sliding motion'. Applying this method to lung image registration results in highly accurate image registration and anatomically plausible estimations of the deformations. The resulting deformation �fields might be further applied to estimate lung ventilation maps. We present a novel approach for estimating regional lung ventilation from dynamic lung CT imaging. Our method combines a supervoxel-based image representation with deformable image registration, performed between peak breathing phases, during which we track changes in intensity for a number of layers of previously extracted supervoxels. Such a region-based approach is expected to be physiologically more consistent with lung anatomy than methods relying on voxel-wise relationships. Our work also presents novel approaches for performing more accurate hyperpolarised 129Xenon MRI (XeMRI) analysis. We propose a multimodal lung image registration enhanced with personalised motion model approach derived from lung 4DCT. The approach with a prior motion model is particularly important for regions where there is not enough information to reliably drive the registration process, as in the case of XeMRI and proton density MRI (pMRI) to CT registration. Subsequently we introduce a framework for breathing motion correction of the dynamic sequence of XeMRI using a lung atlas-based approach. Such a method for the breathing motion correction is expected to facilitate the analysis of temporal lung ventilation.</p

Patch-based lung ventilation estimation using multi-layer supervoxels

Patch-based approaches have received substantial attention over the recent years in medical imaging. One of their potential applications may be to provide more anatomically consistent ventilation maps estimated on dynamic lung CT. An assessment of regional lung function may act as a guide for radiotherapy, ensuring a more accurate treatment plan. This in turn, could spare well-functioning parts of the lungs. We present a novel method for lung ventilation estimation from dynamic lung CT imaging, combining a supervoxel-based image representation with deformations estimated during deformable image registration, performed between peak breathing phases. For this we propose a method that tracks changes of the intensity of previously extracted supervoxels. For the evaluation of the method we calculate correlation of the estimated ventilation maps with static ventilation images acquired from hyperpolarized Xenon129 MRI. We also investigate the influence of different image registration methods used to estimate deformations between the peak breathing phases in the dynamic CT imaging. We show that our method performs favorably to other ventilation estimation methods commonly used in the field, independently of the image registration method applied to dynamic CT. Due to the patch-based approach of our method, it may be physiologically more consistent with lung anatomy than previous methods relying on voxel-wise relationships. In our method the ventilation is estimated for supervoxels, which tend to group spatially close voxels with similar intensity values. The proposed method was evaluated on a dataset consisting of three lung cancer patients undergoing radiotherapy treatment, and this resulted in a correlation of 0.485 with XeMRI ventilation images, compared with 0.393 for the intensity-based approach, 0.231 for the Jacobian-based method and 0.386 for the Hounsfield units averaging method, on average. Within the limitation of the small number of cases analyzed, results suggest that the presented technique may be advantageous for CT-based ventilation estimation. The results showing higher values of correlation of the proposed method demonstrate the potential of our method to more accurately mimic the lung physiology

Supervoxels for graph cuts-based deformable image registration using guided image filtering

We propose combining a supervoxel-based image representation with the concept of graph cuts as an efficient optimization technique for three-dimensional (3-D) deformable image registration. Due to the pixels/voxels-wise graph construction, the use of graph cuts in this context has been mainly limited to two-dimensional (2-D) applications. However, our work overcomes some of the previous limitations by posing the problem on a graph created by adjacent supervoxels, where the number of nodes in the graph is reduced from the number of voxels to the number of supervoxels. We demonstrate how a supervoxel image representation combined with graph cuts-based optimization can be applied to 3-D data. We further show that the application of a relaxed graph representation of the image, followed by guided image filtering over the estimated deformation field, allows us to model "sliding motion." Applying this method to lung image registration results in highly accurate image registration and anatomically plausible estimations of the deformations. Evaluation of our method on a publicly available computed tomography lung image dataset leads to the observation that our approach compares very favorably with state of the art methods in continuous and discrete image registration, achieving target registration error of 1.16 mm on average per landmark

Supervoxels for graph cuts-based deformable image registration using guided image filtering

We propose combining a supervoxel-based image representation with the concept of graph cuts as an efficient optimization technique for three-dimensional (3-D) deformable image registration. Due to the pixels/voxels-wise graph construction, the use of graph cuts in this context has been mainly limited to two-dimensional (2-D) applications. However, our work overcomes some of the previous limitations by posing the problem on a graph created by adjacent supervoxels, where the number of nodes in the graph is reduced from the number of voxels to the number of supervoxels. We demonstrate how a supervoxel image representation combined with graph cuts-based optimization can be applied to 3-D data. We further show that the application of a relaxed graph representation of the image, followed by guided image filtering over the estimated deformation field, allows us to model “sliding motion.” Applying this method to lung image registration results in highly accurate image registration and anatomically plausible estimations of the deformations. Evaluation of our method on a publicly available computed tomography lung image dataset leads to the observation that our approach compares very favorably with state of the art methods in continuous and discrete image registration, achieving target registration error of 1.16 mm on average per landmar

Supervoxels for graph cuts-based deformable image registration using guided image filtering

We propose combining a supervoxel-based image representation with the concept of graph cuts as an efficient optimization technique for three-dimensional (3-D) deformable image registration. Due to the pixels/voxels-wise graph construction, the use of graph cuts in this context has been mainly limited to two-dimensional (2-D) applications. However, our work overcomes some of the previous limitations by posing the problem on a graph created by adjacent supervoxels, where the number of nodes in the graph is reduced from the number of voxels to the number of supervoxels. We demonstrate how a supervoxel image representation combined with graph cuts-based optimization can be applied to 3-D data. We further show that the application of a relaxed graph representation of the image, followed by guided image filtering over the estimated deformation field, allows us to model "sliding motion." Applying this method to lung image registration results in highly accurate image registration and anatomically plausible estimations of the deformations. Evaluation of our method on a publicly available computed tomography lung image dataset leads to the observation that our approach compares very favorably with state of the art methods in continuous and discrete image registration, achieving target registration error of 1.16 mm on average per landmark

Non-local Graph-Based Regularization for Deformable Image Registration

Deformable image registration aims to deliver a plausible spatial transformation between two or more images by solving a highly dimensional, ill-posed optimization problem. Covering the complexity of physiological motion has so far been limited to either generic physical models or local motion regularization models. This paper presents an alternative, graphical regularization model, which captures well the non-local scale of motion, and thus enables to incorporate complex regularization models directly into deformable image registration. In order to build the proposed graph-based regularization, a Minimum Spanning Tree (MST), which represents the underlying tissue physiology in a perceptually meaningful way, is computed first. This is followed by a fast non-local cost aggregation algorithm that performs regularization of the estimated displacement field using the precomputed MST. To demonstrate the advantage of the presented regularization, we embed it into the widely used Demons registration framework. The presented method is shown to improve the accuracy for exhale-inhale CT data pairs