Independent component analysis (ICA) applied to dynamic oxygen-enhanced MRI (OE-MRI) for robust functional lung imaging at 3 T.

PURPOSE: Dynamic lung oxygen-enhanced MRI (OE-MRI) is challenging due to the presence of confounding signals and poor signal-to-noise ratio, particularly at 3 T. We have created a robust pipeline utilizing independent component analysis (ICA) to automatically extract the oxygen-induced signal change from confounding factors to improve the accuracy and sensitivity of lung OE-MRI. METHODS: Dynamic OE-MRI was performed on healthy participants using a dual-echo multi-slice spoiled gradient echo sequence at 3 T and cyclical gas delivery. ICA was applied to each echo within a thoracic mask. The ICA component relating to the oxygen-enhancement signal was automatically identified using correlation analysis. The oxygen-enhancement component was reconstructed, and the percentage signal enhancement (PSE) was calculated. The lung PSE of current smokers was compared with nonsmokers; scan-rescan repeatability, ICA pipeline repeatability, and reproducibility between two vendors were assessed. RESULTS: ICA successfully extracted a consistent oxygen-enhancement component for all participants. Lung tissue and oxygenated blood displayed the opposite oxygen-induced signal enhancements. A significant difference in PSE was observed between the lungs of current smokers and nonsmokers. The scan-rescan repeatability and the ICA pipeline repeatability were good. CONCLUSION: The developed pipeline demonstrated sensitivity to the signal enhancements of the lung tissue and oxygenated blood at 3 T. The difference in lung PSE between current smokers and nonsmokers indicates a likely sensitivity to lung function alterations that may be seen in mild pathology, supporting future use of our methods in patient studies.

Motion estimation and correction for simultaneous PET/MR using SIRF and CIL.

SIRF is a powerful PET/MR image reconstruction research tool for processing data and developing new algorithms. In this research, new developments to SIRF are presented, with focus on motion estimation and correction. SIRF's recent inclusion of the adjoint of the resampling operator allows gradient propagation through resampling, enabling the MCIR technique. Another enhancement enabled registering and resampling of complex images, suitable for MRI. Furthermore, SIRF's integration with the optimization library CIL enables the use of novel algorithms. Finally, SPM is now supported, in addition to NiftyReg, for registration. Results of MR and PET MCIR reconstructions are presented, using FISTA and PDHG, respectively. These demonstrate the advantages of incorporating motion correction and variational and structural priors. This article is part of the theme issue 'Synergistic tomographic image reconstruction: part 2'.

Surrogate-driven respiratory motion model for projection-resolved motion estimation and motion compensated cone-beam CT reconstruction from unsorted projection data.

Objective.As the most common solution to motion artefact for cone-beam CT (CBCT) in radiotherapy, 4DCBCT suffers from long acquisition time and phase sorting error. This issue could be addressed if the motion at each projection could be known, which is a severely ill-posed problem. This study aims to obtain the motion at each time point and motion-free image simultaneously from unsorted projection data of a standard 3DCBCT scan.Approach.Respiration surrogate signals were extracted by the Intensity Analysis method. A general framework was then deployed to fit a surrogate-driven motion model that characterized the relation between the motion and surrogate signals at each time point. Motion model fitting and motion compensated reconstruction were alternatively and iteratively performed. Stochastic subset gradient based method was used to significantly reduce the computation time. The performance of our method was comprehensively evaluated through digital phantom simulation and also validated on clinical scans from six patients.Results.For digital phantom experiments, motion models fitted with ground-truth or extracted surrogate signals both achieved a much lower motion estimation error and higher image quality, compared with non motion-compensated results.For the public SPARE Challenge datasets, more clear lung tissues and less blurry diaphragm could be seen in the motion compensated reconstruction, comparable to the benchmark 4DCBCT images but with a higher temporal resolution. Similar results were observed for two real clinical 3DCBCT scans.Significance.The motion compensated reconstructions and motion models produced by our method will have direct clinical benefit by providing more accurate estimates of the delivered dose and ultimately facilitating more accurate radiotherapy treatments for lung cancer patients.

Respiratory motion modelling for MR-guided lung cancer radiotherapy: model development and geometric accuracy evaluation.

Objective.Respiratory motion of lung tumours and adjacent structures is challenging for radiotherapy. Online MR-imaging cannot currently provide real-time volumetric information of the moving patient anatomy, therefore limiting precise dose delivery, delivered dose reconstruction, and downstream adaptation methods.Approach.We tailor a respiratory motion modelling framework towards an MR-Linac workflow to estimate the time-resolved 4D motion from real-time data. We develop a multi-slice acquisition scheme which acquires thick, overlapping 2D motion-slices in different locations and orientations, interleaved with 2D surrogate-slices from a fixed location. The framework fits a motion model directly to the input data without the need for sorting or binning to account for inter- and intra-cycle variation of the breathing motion. The framework alternates between model fitting and motion-compensated super-resolution image reconstruction to recover a high-quality motion-free image and a motion model. The fitted model can then estimate the 4D motion from 2D surrogate-slices. The framework is applied to four simulated anthropomorphic datasets and evaluated against known ground truth anatomy and motion. Clinical applicability is demonstrated by applying our framework to eight datasets acquired on an MR-Linac from four lung cancer patients.Main results.The framework accurately reconstructs high-quality motion-compensated 3D images with 2 mm3isotropic voxels. For the simulated case with the largest target motion, the motion model achieved a mean deformation field error of 1.13 mm. For the patient cases residual error registrations estimate the model error to be 1.07 mm (1.64 mm), 0.91 mm (1.32 mm), and 0.88 mm (1.33 mm) in superior-inferior, anterior-posterior, and left-right directions respectively for the building (application) data.Significance.The motion modelling framework estimates the patient motion with high accuracy and accurately reconstructs the anatomy. The image acquisition scheme can be flexibly integrated into an MR-Linac workflow whilst maintaining the capability of online motion-management strategies based on cine imaging such as target tracking and/or gating.

Data driven surrogate signal extraction for dynamic PET using selective PCA: time windows versus the combination of components.

Objective.Respiratory motion correction is beneficial in positron emission tomography (PET), as it can reduce artefacts caused by motion and improve quantitative accuracy. Methods of motion correction are commonly based on a respiratory trace obtained through an external device (like the real time position management system) or a data driven method, such as those based on dimensionality reduction techniques (for instance principal component analysis (PCA)). PCA itself being a linear transformation to the axis of greatest variation. Data driven methods have the advantage of being non-invasive, and can be performed post-acquisition. However, their main downside being that they are adversely affected by the tracer kinetics of the dynamic PET acquisition. Therefore, they are mostly limited to static PET acquisitions. This work seeks to extend on existing PCA-based data-driven motion correction methods, to allow for their applicability to dynamic PET imaging.Approach.The methods explored in this work include; a moving window approach (similar to the Kinetic Respiratory Gating method from Schleyeret al(2014)), extrapolation of the principal component from later time points to earlier time points, and a method to score, select, and combine multiple respiratory components. The resulting respiratory traces were evaluated on 22 data sets from a dynamic [18F]-FDG study on patients with idiopathic pulmonary fibrosis. This was achieved by calculating their correlation with a surrogate signal acquired using a real time position management system.Main results.The results indicate that all methods produce better surrogate signals than when applying conventional PCA to dynamic data (for instance, a higher correlation with a gold standard respiratory trace). Extrapolating a late time point principal component produced more promising results than using a moving window. Scoring, selecting, and combining components held benefits over all other methods.Significance.This work allows for the extraction of a surrogate signal from dynamic PET data earlier in the acquisition and with a greater accuracy than previous work. This potentially allows for numerous other methods (for instance, respiratory motion correction) to be applied to this data (when they otherwise could not be previously used).

CT colonography: external clinical validation of an algorithm for computer-assisted prone and supine registration.

PURPOSE: To perform external validation of a computer-assisted registration algorithm for prone and supine computed tomographic (CT) colonography and to compare the results with those of an existing centerline method. MATERIALS AND METHODS: All contributing centers had institutional review board approval; participants provided informed consent. A validation sample of CT colonographic examinations of 51 patients with 68 polyps (6-55 mm) was selected from a publicly available, HIPAA compliant, anonymized archive. No patients were excluded because of poor preparation or inadequate distension. Corresponding prone and supine polyp coordinates were recorded, and endoluminal surfaces were registered automatically by using a computer algorithm. Two observers independently scored three-dimensional endoluminal polyp registration success. Results were compared with those obtained by using the normalized distance along the colonic centerline (NDACC) method. Pairwise Wilcoxon signed rank tests were used to compare gross registration error and McNemar tests were used to compare polyp conspicuity. RESULTS: Registration was possible in all 51 patients, and 136 paired polyp coordinates were generated (68 polyps) to test the algorithm. Overall mean three-dimensional polyp registration error (mean ± standard deviation, 19.9 mm ± 20.4) was significantly less than that for the NDACC method (mean, 27.4 mm ± 15.1; P = .001). Accuracy was unaffected by colonic segment (P = .76) or luminal collapse (P = .066). During endoluminal review by two observers (272 matching tasks, 68 polyps, prone to supine and supine to prone coordinates), 223 (82%) polyp matches were visible (120° field of view) compared with just 129 (47%) when the NDACC method was used (P < .001). By using multiplanar visualization, 48 (70%) polyps were visible after scrolling ± 15 mm in any multiplanar axis compared with 16 (24%) for NDACC (P < .001). CONCLUSION: Computer-assisted registration is more accurate than the NDACC method for mapping the endoluminal surface and matching the location of polyps in corresponding prone and supine CT colonographic acquisitions.

Applicability and usage of dose mapping/accumulation in radiotherapy.

Dose mapping/accumulation (DMA) is a topic in radiotherapy (RT) for years, but has not yet found its widespread way into clinical RT routine. During the ESTRO Physics workshop 2021 on "commissioning and quality assurance of deformable image registration (DIR) for current and future RT applications", we built a working group on DMA from which we present the results of our discussions in this article. Our aim in this manuscript is to shed light on the current situation of DMA in RT and to highlight the issues that hinder consciously integrating it into clinical RT routine. As a first outcome of our discussions, we present a scheme where representative RT use cases are positioned, considering expected anatomical variations and the impact of dose mapping uncertainties on patient safety, which we have named the DMA landscape (DMAL). This tool is useful for future reference when DMA applications get closer to clinical day-to-day use. Secondly, we discussed current challenges, lightly touching on first-order effects (related to the impact of DIR uncertainties in dose mapping), and focusing in detail on second-order effects often dismissed in the current literature (as resampling and interpolation, quality assurance considerations, and radiobiological issues). Finally, we developed recommendations, and guidelines for vendors and users. Our main point include: Strive for context-driven DIR (by considering their impact on clinical decisions/judgements) rather than perfect DIR; be conscious of the limitations of the implemented DIR algorithm; and consider when dose mapping (with properly quantified uncertainties) is a better alternative than no mapping.

Toward semi-automatic biologically effective dose treatment plan optimisation for Gamma Knife radiosurgery.

Objective.Dose-rate effects in Gamma Knife radiosurgery treatments can lead to varying biologically effective dose (BED) levels for the same physical dose. The non-convex BED model depends on the delivery sequence and creates a non-trivial treatment planning problem. We investigate the feasibility of employing inverse planning methods to generate treatment plans exhibiting desirable BED characteristics using the per iso-centre beam-on times and delivery sequence.Approach.We implement two dedicated optimisation algorithms. One approach relies on mixed-integer linear programming (MILP) using a purposely developed convex underestimator for the BED to mitigate local minima issues at the cost of computational complexity. The second approach (local optimisation) is faster and potentially usable in a clinical setting but more prone to local minima issues. It sequentially executes the beam-on time (quasi-Newton method) and sequence optimisation (local search algorithm). We investigate the trade-off between time to convergence and solution quality by evaluating the resulting treatment plans' objective function values and clinical parameters. We also study the treatment time dependence of the initial and optimised plans using BED95(BED delivered to 95% of the target volume) values.Main results.When optimising the beam-on times and delivery sequence, the local optimisation approach converges several orders of magnitude faster than the MILP approach (minutes versus hours-days) while typically reaching within 1.2% (0.02-2.08%) of the final objective function value. The quality parameters of the resulting treatment plans show no meaningful difference between the local and MILP optimisation approaches. The presented optimisation approaches remove the treatment time dependence observed in the original treatment plans, and the chosen objectives successfully promote more conformal treatments.Significance.We demonstrate the feasibility of using an inverse planning approach within a reasonable time frame to ensure BED-based objectives are achieved across varying treatment times and highlight the prospect of further improvements in treatment plan quality.

A Novel and Automated Approach to Classify Radiation Induced Lung Tissue Damage on CT Scans.

Radiation-induced lung damage (RILD) is a common side effect of radiotherapy (RT). The ability to automatically segment, classify, and quantify different types of lung parenchymal change is essential to uncover underlying patterns of RILD and their evolution over time. A RILD dedicated tissue classification system was developed to describe lung parenchymal tissue changes on a voxel-wise level. The classification system was automated for segmentation of five lung tissue classes on computed tomography (CT) scans that described incrementally increasing tissue density, ranging from normal lung (Class 1) to consolidation (Class 5). For ground truth data generation, we employed a two-stage data annotation approach, akin to active learning. Manual segmentation was used to train a stage one auto-segmentation method. These results were manually refined and used to train the stage two auto-segmentation algorithm. The stage two auto-segmentation algorithm was an ensemble of six 2D Unets using different loss functions and numbers of input channels. The development dataset used in this study consisted of 40 cases, each with a pre-radiotherapy, 3-, 6-, 12-, and 24-month follow-up CT scans (n = 200 CT scans). The method was assessed on a hold-out test dataset of 6 cases (n = 30 CT scans). The global Dice score coefficients (DSC) achieved for each tissue class were: Class (1) 99% and 98%, Class (2) 71% and 44%, Class (3) 56% and 26%, Class (4) 79% and 47%, and Class (5) 96% and 92%, for development and test subsets, respectively. The lowest values for the test subsets were caused by imaging artefacts or reflected subgroups that occurred infrequently and with smaller overall parenchymal volumes. We performed qualitative evaluation on the test dataset presenting manual and auto-segmentation to a blinded independent radiologist to rate them as 'acceptable', 'minor disagreement' or 'major disagreement'. The auto-segmentation ratings were similar to the manual segmentation, both having approximately 90% of cases rated as acceptable. The proposed framework for auto-segmentation of different lung tissue classes produces acceptable results in the majority of cases and has the potential to facilitate future large studies of RILD.

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.

Registration of the endoluminal surfaces of the colon derived from prone and supine CT colonography.

PURPOSE: Computed tomographic (CT) colonography is a relatively new technique for detecting bowel cancer or potentially precancerous polyps. CT scanning is combined with three-dimensional (3D) image reconstruction to produce a virtual endoluminal representation similar to optical colonoscopy. Because retained fluid and stool can mimic pathology, CT data are acquired with the bowel cleansed and insufflated with gas and patient in both prone and supine positions. Radiologists then match visually endoluminal locations between the two acquisitions in order to determine whether apparent pathology is real or not. This process is hindered by the fact that the colon, essentially a long tube, can undergo considerable deformation between acquisitions. The authors present a novel approach to automatically establish spatial correspondence between prone and supine endoluminal colonic surfaces after surface parameterization, even in the case of local colon collapse. METHODS: The complexity of the registration task was reduced from a 3D to a 2D problem by mapping the surfaces extracted from prone and supine CT colonography onto a cylindrical parameterization. A nonrigid cylindrical registration was then performed to align the full colonic surfaces. The curvature information from the original 3D surfaces was used to determine correspondence. The method can also be applied to cases with regions of local colonic collapse by ignoring the collapsed regions during the registration. RESULTS: Using a development set, suitable parameters were found to constrain the cylindrical registration method. Then, the same registration parameters were applied to a different set of 13 validation cases, consisting of 8 fully distended cases and 5 cases exhibiting multiple colonic collapses. All polyps present were well aligned, with a mean (+/- std. dev.) registration error of 5.7 (+/- 3.4) mm. An additional set of 1175 reference points on haustral folds spread over the full endoluminal colon surfaces resulted in an error of 7.7 (+/- 7.4) mm. Here, 82% of folds were aligned correctly after registration with a further 15% misregistered by just onefold. CONCLUSIONS: The proposed method reduces the 3D registration task to a cylindrical registration representing the endoluminal surface of the colon. Our algorithm uses surface curvature information as a similarity measure to drive registration to compensate for the large colorectal deformations that occur between prone and supine data acquisitions. The method has the potential to both enhance polyp detection and decrease the radiologist's interpretation time.

Technical Note: Four-dimensional deformable digital phantom for MRI sequence development.

PURPOSE: MR-guided radiotherapy has different requirements for the images than diagnostic radiology, thus requiring development of novel imaging sequences. MRI simulation is an excellent tool for optimizing these new sequences; however, currently available software does not provide all the necessary features. In this paper, we present a digital framework for testing MRI sequences that incorporates anatomical structure, respiratory motion, and realistic presentation of MR physics. METHODS: The extended Cardiac-Torso (XCAT) software was used to create T1 , T2 , and proton density maps that formed the anatomical structure of the phantom. Respiratory motion model was based on the XCAT deformation vector fields, modified to create a motion model driven by a respiration signal. MRI simulation was carried out with JEMRIS, an open source Bloch simulator. We developed an extension for JEMRIS, which calculates the motion of each spin independently, allowing for deformable motion. RESULTS: The performance of the framework was demonstrated through simulating the acquisition of a two-dimensional (2D) cine and demonstrating expected motion ghosts from T2 weighted spin echo acquisitions with different respiratory patterns. All simulations were consistent with behavior previously described in literature. Simulations with deformable motion were not more time consuming than with rigid motion. CONCLUSIONS: We present a deformable four-dimensional (4D) digital phantom framework for MR sequence development. The framework incorporates anatomical structure, realistic breathing patterns, deformable motion, and Bloch simulation to achieve accurate simulation of MRI. This method is particularly relevant for testing novel imaging sequences for the purpose of MR-guided radiotherapy in lungs and abdomen.

The impact of unscheduled gaps and iso-centre sequencing on the biologically effective dose in Gamma Knife radiosurgery.

PURPOSE: Establish the impact of iso-centre sequencing and unscheduled gaps in Gamma Knife® (GK) radiosurgery on the biologically effective dose (BED). METHODS: A BED model was used to study BED values on the prescription iso-surface of patients treated with GK Perfexion™ (Vestibular Schwannoma). The effect of a 15 min gap, simulated at varying points in the treatment delivery, and adjustments to the sequencing of iso-centre delivery, based on average dose-rate, was quantified in terms of the impact on BED. RESULTS: Depending on the position of the gap and the average dose-rate profiles, the mean BED values were decreased by 0.1% to 9.9% of the value in the original plan. A heuristic approach to iso-centre sequencing showed variations in BED of up to 14.2%, relative to the mean BED of the original sequence. CONCLUSION: The treatment variables, like the iso-centre sequence and unscheduled gaps, should be considered during GK radiosurgery treatments.

Clinical practice vs. state-of-the-art research and future visions: Report on the 4D treatment planning workshop for particle therapy - Edition 2018 and 2019.

The 4D Treatment Planning Workshop for Particle Therapy, a workshop dedicated to the treatment of moving targets with scanned particle beams, started in 2009 and since then has been organized annually. The mission of the workshop is to create an informal ground for clinical medical physicists, medical physics researchers and medical doctors interested in the development of the 4D technology, protocols and their translation into clinical practice. The 10th and 11th editions of the workshop took place in Sapporo, Japan in 2018 and Krakow, Poland in 2019, respectively. This review report from the Sapporo and Krakow workshops is structured in two parts, according to the workshop programs. The first part comprises clinicians and physicists review of the status of 4D clinical implementations. Corresponding talks were given by speakers from five centers around the world: Maastro Clinic (The Netherlands), University Medical Center Groningen (The Netherlands), MD Anderson Cancer Center (United States), University of Pennsylvania (United States) and The Proton Beam Therapy Center of Hokkaido University Hospital (Japan). The second part is dedicated to novelties in 4D research, i.e. motion modelling, artificial intelligence and new technologies which are currently being investigated in the radiotherapy field.

Consistent and invertible deformation vector fields for a breathing anthropomorphic phantom: a post-processing framework for the XCAT phantom.

Breathing motion is challenging for radiotherapy planning and delivery. This requires advanced four-dimensional (4D) imaging and motion mitigation strategies and associated validation tools with known deformations. Numerical phantoms such as the XCAT provide reproducible and realistic data for simulation-based validation. However, the XCAT generates partially inconsistent and non-invertible deformations where tumours remain rigid and structures can move through each other. We address these limitations by post-processing the XCAT deformation vector fields (DVF) to generate a breathing phantom with realistic motion and quantifiable deformation. An open-source post-processing framework was developed that corrects and inverts the XCAT-DVFs while preserving sliding motion between organs. Those post-processed DVFs are used to warp the first XCAT-generated image to consecutive time points providing a 4D phantom with a tumour that moves consistently with the anatomy, the ability to scale lung density as well as consistent and invertible DVFs. For a regularly breathing case, the inverse consistency of the DVFs was verified and the tumour motion was compared to the original XCAT. The generated phantom and DVFs were used to validate a motion-including dose reconstruction (MIDR) method using isocenter shifts to emulate rigid motion. Differences between the reconstructed doses with and without lung density scaling were evaluated. The post-processing framework produced DVFs with a maximum [Formula: see text]-percentile inverse-consistency error of 0.02 mm. The generated phantom preserved the dominant sliding motion between the chest wall and inner organs. The tumour of the original XCAT phantom preserved its trajectory while deforming consistently with the underlying tissue. The MIDR was compared to the ground truth dose reconstruction illustrating its limitations. MIDR with and without lung density scaling resulted in small dose differences up to 1 Gy (prescription 54 Gy). The proposed open-source post-processing framework overcomes important limitations of the original XCAT phantom and makes it applicable to a wider range of validation applications within radiotherapy.

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.

Evaluation of MRI-derived surrogate signals to model respiratory motion.

An MR-Linac can provide motion information of tumour and organs-at-risk before, during, and after beam delivery. However, MR imaging cannot provide real-time high-quality volumetric images which capture breath-to-breath variability of respiratory motion. Surrogate-driven motion models relate the motion of the internal anatomy to surrogate signals, thus can estimate the 3D internal motion from these signals. Internal surrogate signals based on patient anatomy can be extracted from 2D cine-MR images, which can be acquired on an MR-Linac during treatment, to build and drive motion models. In this paper we investigate different MRI-derived surrogate signals, including signals generated by applying principal component analysis to the image intensities, or control point displacements derived from deformable registration of the 2D cine-MR images. We assessed the suitability of the signals to build models that can estimate the motion of the internal anatomy, including sliding motion and breath-to-breath variability. We quantitatively evaluated the models by estimating the 2D motion in sagittal and coronal slices of 8 lung cancer patients, and comparing them to motion measurements obtained from image registration. For sagittal slices, using the first and second principal components on the control point displacements as surrogate signals resulted in the highest model accuracy, with a mean error over patients around 0.80 mm which was lower than the in-plane resolution. For coronal slices, all investigated signals except the skin signal produced mean errors over patients around 1 mm. These results demonstrate that surrogate signals derived from 2D cine-MR images, including those generated by applying principal component analysis to the image intensities or control point displacements, can accurately model the motion of the internal anatomy within a single sagittal or coronal slice. This implies the signals should also be suitable for modelling the 3D respiratory motion of the internal anatomy.

Long term radiological features of radiation-induced lung damage.

PURPOSE: To describe the radiological findings of radiation-induced lung damage (RILD) present on CT imaging of lung cancer patients 12 months after radical chemoradiation. MATERIAL AND METHODS: Baseline and 12-month CT scans of 33 patients were reviewed from a phase I/II clinical trial of isotoxic chemoradiation (IDEAL CRT). CT findings were scored in three categories derived from eleven sub-categories: (1) parenchymal change, defined as the presence of consolidation, ground-glass opacities (GGOs), traction bronchiectasis and/or reticulation; (2) lung volume reduction, identified through reduction in lung height and/or distortions in fissures, diaphragm, anterior junction line and major airways anatomy, and (3) pleural changes, either thickening and/or effusion. RESULTS: Six patients were excluded from the analysis due to anatomical changes caused by partial lung collapse and abscess. All remaining 27 patients had radiological evidence of lung damage. The three categories, parenchymal change, shrinkage and pleural change were present in 100%, 96% and 82% respectively. All patients had at least two categories of change present and 72% all three. GGOs, reticulation and traction bronchiectasis were present in 44%, 52% and 37% of patients. CONCLUSIONS: Parenchymal change, lung shrinkage and pleural change are present in a high proportion of patients and are frequently identified in RILD. GGOs, reticulation and traction bronchiectasis are common at 12 months but not diagnostic.

Novel CT-Based Objective Imaging Biomarkers of Long-Term Radiation-Induced Lung Damage.

PURPOSE: Recent improvements in lung cancer survival have spurred an interest in understanding and minimizing long-term radiation-induced lung damage (RILD). However, there are still no objective criteria to quantify RILD, leading to variable reporting across centers and trials. We propose a set of objective imaging biomarkers for quantifying common radiologic findings observed 12 months after lung cancer radiation therapy. METHODS AND MATERIALS: Baseline and 12-month computed tomography (CT) scans of 27 patients from a phase 1/2 clinical trial of isotoxic chemoradiation were included in this study. To detect and measure the severity of RILD, 12 quantitative imaging biomarkers were developed. The biomarkers describe basic CT findings, including parenchymal change, volume reduction, and pleural change. The imaging biomarkers were implemented as semiautomated image analysis pipelines and were assessed against visual assessment of the occurrence of each change. RESULTS: Most of the biomarkers were measurable in each patient. The continuous nature of the biomarkers allows objective scoring of severity for each patient. For each imaging biomarker, the cohort was split into 2 groups according to the presence or absence of the biomarker by visual assessment, testing the hypothesis that the imaging biomarkers were different in the 2 groups. All features were statistically significant except for rotation of the main bronchus and diaphragmatic curvature. Most of the biomarkers were not strongly correlated with each other, suggesting that each of the biomarkers is measuring a separate element of RILD pathology. CONCLUSIONS: We developed objective CT-based imaging biomarkers that quantify the severity of radiologic lung damage after radiation therapy. These biomarkers are representative of typical radiologic findings of RILD.

Super-resolution T2-weighted 4D MRI for image guided radiotherapy.

BACKGROUND AND PURPOSE: The superior soft-tissue contrast of 4D-T2w MRI motivates its use for delineation in radiotherapy treatment planning. We address current limitations of slice-selective implementations, including thick slices and artefacts originating from data incompleteness and variable breathing. MATERIALS AND METHODS: A method was developed to calculate midposition and 4D-T2w images of the whole thorax from continuously acquired axial and sagittal 2D-T2w MRI (1.5 × 1.5 × 5.0 mm3). The method employed image-derived respiratory surrogates, deformable image registration and super-resolution reconstruction. Volunteer imaging and a respiratory motion phantom were used for validation. The minimum number of dynamic acquisitions needed to calculate a representative midposition image was investigated by retrospectively subsampling the data (10-30 dynamic acquisitions). RESULTS: Super-resolution 4D-T2w MRI (1.0 × 1.0 × 1.0 mm3, 8 respiratory phases) did not suffer from data incompleteness and exhibited reduced stitching artefacts compared to sorted multi-slice MRI. Experiments using a respiratory motion phantom and colour-intensity projection images demonstrated a minor underestimation of the motion range. Midposition diaphragm differences in retrospectively subsampled acquisitions were <1.1 mm compared to the full dataset. 10 dynamic acquisitions were found sufficient to generate midposition MRI. CONCLUSIONS: A motion-modelling and super-resolution method was developed to calculate high quality 4D/midposition T2w MRI from orthogonal 2D-T2w MRI.