Development and testing of extra-cranial tumour tracking methods for intra-fraction organ motion compensation in particle radiation therapy

Le tecniche di scansione attiva dei fasci di particelle in adroterapia consentono una miglior conformità della dose al volume bersaglio, ma risultano altamente sensibili al movimento intra-frazione della lesione legato principalmente al respiro. L'opportunità di estendere tali tecniche al trattamento di tumori extra-cranici richiede necessariamente l'applicazione di strategie adeguate per la compensazione dell'organ motion. Lo scopo di questa tesi è consistito nello sviluppare e testare un metodo di tumour tracking basato su superfici, per la localizzazione dinamica e il monitoraggio continuo di lesioni toraco-addominali durante trattamenti radioterapici. L'approccio proposto si basa su surrogati esterni di superficie ottenuti mediante dispositivi ottici non-invasivi, e su modelli adattativi del movimento respiratorio derivati da immagini di pianificazione risolte in tempo e da sistemi in-room di imaging a raggi X. Applicando algoritmi di registrazione con deformazione alle immagini di Tomografia Computerizzata 4D (4D CT), viene stimato un modello di movimento della lesione paziente-specifico, parametrizzato in funzione della linea di base, ampiezza e fase respiratoria. La linea di base è adattata a ciascuna frazione di trattamento in base alle informazioni sulla localizzazione del target derivate da immagini volumetriche di Cone Beam CT (CBCT). L'ampiezza e la fase respiratoria sono ricavate dal movimento della superficie esterna, acquisito mediante sistemi 3D di imaging di superficie. Vengono applicati algoritmi di registrazione con deformazione di superfici per derivare la corrispondenza spaziale tra superfici ottiche. Le traiettorie ottenute di tutti i punti della superficie toraco-addominale sono sintetizzate in un unico segnale respiratorio surrogato. I valori istantanei di ampiezza e fase sono estratti dal segnale surrogato confrontando il movimento della superficie durante le fasi di pianificazione e di trattamento. I parametri respiratori adattati vengono infine integrati nel modello 4D CT per stimare il movimento 3D intra-frazione della lesione. Il metodo di tumour tracking sviluppato è stato testato su un database clinico di sette pazienti con lesioni al polmone, che include informazioni sincronizzate sul movimento respiratorio della lesione e della superficie esterna durante scansioni CBCT. Per ciascun paziente sono stati analizzati circa 30 secondi di acquisizione sincronizzata di proiezioni CBCT e superfici ottiche, acquisite con il sistema VisionRT. Le traiettorie delle lesioni stimate dallo spostamento della superficie, in combinazione con il modello di movimento 4D CT, sono state confrontate con le traiettorie reali del target, identificato su immagini CBCT attraverso una tecnica sviluppata di esaltazione del contrasto di tumori su proiezioni a raggi X. Le differenze assolute risultanti tra il movimento reale e stimato del target sono comprese tra 0.7 e 2.4 mm, con valori mediani di 1.5 mm sia lungo le dimensioni orizzontali e verticali dell'immagine. Gli sfasamenti misurati non superano il 7% della lunghezza del ciclo respiratorio. Il metodo di tumour tracking proposto si è dimostrato efficace nello stimare il movimento del target a partire dallo spostamento della superficie esterna, anche in presenza di irregolarità respiratorie. Ci si aspetta che le innovazioni metodologiche introdotte, relative all'utilizzo di modelli di movimento adattativi paziente-specifici e alla ridondanza di dati di superficie ottenuti da scansioni ottiche, migliorino l'accuratezza e la robustezza delle tecniche di targeting per la compensazione dell'organ motion intra-frazione, consentendo potenzialmente di estendere i metodi di scansione attiva in adroterapia al trattamento di tumori extra-cranici.Active scanning techniques in particle radiation therapy provide an improved dose conformity to the target volume, but feature a high sensitivity to intra-fraction organ motion mainly due to breathing. The opportunity to extend these advantageous techniques to the treatment of extra-cranial moving tumours necessarily requires the application of adequate strategies for organ motion compensation. The aim of this thesis was to develop and evaluate a surface-based tumour tracking method, for the dynamic localization and continuous monitoring of thoraco-abdominal lesions during radiotherapy treatments. The proposed approach is based on external surface surrogates estimated from non-invasive optical devices, and on adaptive breathing motion models derived from time-resolved planning and in-room X-ray imaging systems. A patient-specific motion model, parameterized as a function of the respiratory tumour baseline, amplitude and phase, is estimated from 4D Computed Tomography (CT) planning images by applying deformable registration algorithms. The tumour baseline is adapted at each treatment fraction according to the daily information on target localization derived from volumetric Cone Beam CT (CBCT) images. The breathing amplitude and phase parameters are retrieved from the external surface motion, acquired by means of 3D surface imaging systems. Deformable mesh registration algorithms are applied to derive the spatial correspondence between markerless optical surfaces. The obtained trajectories of all thoraco-abdominal surface points are summarized into a single respiratory surrogate signal. The instantaneous values of the breathing amplitude and phase are extracted from the surrogate signal by comparing surface motion during treatment planning and delivery phases. The adapted breathing parameters are finally integrated in the 4D CT motion model in order to estimate the intra-fraction 3D target motion. The developed tumour tracking method was tested on a clinical database of seven lung cancer patients, including the synchronized information on the external surface and internal tumour breathing motion during CBCT scans. About 30 seconds of synchronized acquisition of CBCT projections and optical surfaces, captured with the VisionRT system, were analyzed for each patient. The lung tumour trajectories estimated from surface displacement combined with the a priori 4D CT motion model were compared to the real target trajectories, identified on CBCT images through a novel developed technique of tumour-contrast enhancement in X-ray projections. The resulting absolute differences between real and estimated target motion ranged between 0.7 and 2.4 mm, with median values of 1.5 mm both along the horizontal and vertical image dimensions. The measured phase shifts did not exceed 7% of the breathing cycle length. The proposed tumour tracking method proved to be effective in estimating target motion from the external surface displacement even in presence of breathing irregularities. The innovative methodological aspects, related to the use of patient-specific adaptive motion models and to the redundancy of markerless surface data from optical scans, are put forward to improve the accuracy and robustness of targeting techniques for intra-fraction organ motion compensation, potentially allowing the extension of active scanning particle therapy methods to the treatment of extra-cranial moving tumours.DIPARTIMENTO DI ELETTRONICA, INFORMAZIONE E BIOINGEGNERIA25PEDOTTI, ANTONIOSIGNORINI, MARIA GABRIELL

An image-based method to synchronize cone-beam CT and optical surface tracking

open5siThe integration of in-room X-ray imaging and optical surface tracking has gained increasing importance in the field of image guided radiotherapy (IGRT). An essential step for this integration consists of temporally synchronizing the acquisition of X-ray projections and surface data. We present an image-based method for the synchronization of cone-beam computed tomography (CBCT) and optical surface systems, which does not require the use of additional hardware. The method is based on optically tracking the motion of a component of the CBCT/gantry unit, which rotates during the acquisition of the CBCT scan. A calibration procedure was implemented to relate the position of the rotating component identified by the optical system with the time elapsed since the beginning of the CBCT scan, thus obtaining the temporal correspondence between the acquisition of X-ray projections and surface data. The accuracy of the proposed synchronization method was evaluated on a motorized moving phantom, performing eight simultaneous acquisitions with an Elekta Synergy CBCT machine and the AlignRT optical device. The median time difference between the sinusoidal peaks of phantom motion signals extracted from the synchronized CBCT and AlignRT systems ranged between -3.1 and 12.9 msec, with a maximum interquartile range of 14.4 msec. The method was also applied to clinical data acquired from seven lung cancer patients, demonstrating the potential of the proposed approach in estimating the individual and daily variations in respiratory parameters and motion correlation of internal and external structures. The presented synchronization method can be particularly useful for tumor tracking applications in extracranial radiation treatments, especially in the field of patient-specific breathing models, based on the correlation between internal tumor motion and external surface surrogates.Fassi, Aurora; Schaerer, Joël; Riboldi, Marco; Sarrut, David; Baroni, GuidoFassi, Aurora; Schaerer, Joël; Riboldi, Marco; Sarrut, David; Baroni, Guid

Physics-Aware POD method for cost-effective high-fidelity PGET simulations of Water-Water Energetic Reactor irradiated fuels

The Passive Gamma Emission Tomography (PGET) system serves to verify spent nuclear fuel and detect pin-level diversions for international nuclear safeguards. Real measurements in the form of sinograms are necessary to test and enhance PGET performance, but they are both costly and scarce. High-fidelity Monte Carlo simulations can generate realistic data, yet they are computationally intensive, requiring all angular views (typically 360, one per degree, or even 720, one per half degree). This paper discusses how the Physics-Aware Proper Orthogonal Decomposition (PA-POD) method recently developed by our group can reconstruct a full Water–Water Energetic Reactor (VVER) sinogram from a limited number of high-fidelity angular views, significantly reducing computational costs. This paper reports on the method’s performance, removal of the ring artifact benefits, and the procedure for constructing a comprehensive PGET library of relevant cases

Bridging imaging-based in vitro methods from biomedical research to regulatory toxicology

Imaging technologies are being increasingly used in biomedical research and experimental toxicology to gather morphological and functional information from cellular models. There is a concrete opportunity of incorporating imaging-based in vitro methods in international guidelines to respond to regulatory requirements with human relevant data. To translate these methods from R&amp;D to international regulatory acceptance, the community needs to implement test methods under quality management systems, assess inter-laboratory transferability, and demonstrate data reliability and robustness. This article summarises current challenges associated with image acquisition, image analysis, including artificial intelligence, and data management of imaging-based methods, with examples from the developmental neurotoxicity in vitro battery and phenotypic profiling assays. The article includes considerations on specific needs and potential solutions to design and implement future validation and transferability studies.</p

Current treatment in macrophage activation syndrome worldwide: a systematic literature review to inform the METAPHOR project

Objective: To assess current treatment in macrophage activation syndrome (MAS) worldwide and to highlight any areas of major heterogeneity of practice. Methods: A systematic literature search was performed in both EMBASE and PubMed databases. Paper screening was done by two independent teams based on agreed criteria. Data extraction was standardized following the PICO framework. A panel of experts assessed paper validity, using the Joanna Briggs Institute appraisal tools and category of evidence (CoE) according to EULAR procedure. Results: Fifty-seven papers were finally included (80% retrospective case-series), describing 1148 patients with MAS: 889 systemic juvenile idiopathic arthritis (sJIA), 137 systemic lupus erythematosus (SLE), 69 Kawasaki disease (KD) and 53 other rheumatological conditions. Fourteen and 11 studies specified data on MAS associated to SLE and KD, respectively. All papers mentioned glucocorticoids (GCs), mostly methylprednisolone and prednisolone (90%); dexamethasone was used in 7% of patients. Ciclosporin was reported in a wide range of patients according to different cohorts. Anakinra was used in 179 MAS patients, with a favourable outcome in 83% of sJIA-MAS. Etoposide was described by 11 studies, mainly as part of HLH-94/04 protocol. Emapalumab was the only medication tested in a clinical trial in 14 sJIA-MAS, with 93% of MAS remission. Ruxolitinib was the most reported Janus kinase inhibitor in MAS. Conclusion: High-dose GCs together with IL-1 and IFN gamma inhibitors have shown efficacy in MAS, especially in sJIA-associated MAS. However, the global level of evidence on MAS treatment, especially in other conditions, is still poor and requires standardized studies to be confirme

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10&nbsp;years; 78.2% included were male with a median age of 37&nbsp;years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

DEVICE FOR MONITORING POSITION AND MOVEMENTS OF AN EYE, PARTICULARLY SUITABLE FOR OCULAR RADIOTHERAPY

The present invention is about a device for non-invasive monitoring of an eye position and ocular movements of a patient, comprising: - a housing body (2) having at least one through opening (2a); - a plurality of light sources (3) housed in said housing body (2); - a plurality of sensor means (4) housed in said housing body (2); - deflector means (6) for invisible radiation (RL) supplied, in use, by said plurality of light sources (3) and reflected by said eye (O) under examination; - support means (8) that can be adjusted for said housing body (2); - at least one program data processing and control unit (9). The support means (8) can be adjusted in such a way that the through opening (2a) of the housing body (2) can be placed at the eye (O) under examination so that the invisible radiation hits the eye (O) frontally. The program data processing and control unit (9) is designed to calculate instant-by-instant the position and orientation of a suitable three-dimensional reference system integral with the eye with respect to a predetermined three-dimensional reference system

Tumour tracking method based on a 4D CT breathing motion model driven by an external surface surrogate

International audiencePurpose To develop a tumor tracking method based on a surrogate-driven motion model, which provides noninvasive dynamic localization of extracranial targets for the compensation of respiration-induced intrafraction motion in high-precision radiation therapy.Methods and Materials The proposed approach is based on a patient-specific breathing motion model, derived a priori from 4-dimensional planning computed tomography (CT) images. Model parameters (respiratory baseline, amplitude, and phase) are retrieved and updated at each treatment fraction according to in-room radiography acquisition and optical surface imaging. The baseline parameter is adapted to the interfraction variations obtained from the daily cone beam (CB) CT scan. The respiratory amplitude and phase are extracted from an external breathing surrogate, estimated from the displacement of the patient thoracoabdominal surface, acquired with a noninvasive surface imaging device. The developed method was tested on a database of 7 lung cancer patients, including the synchronized information on internal and external respiratory motion during a CBCT scan.Results About 30 seconds of simultaneous acquisition of CBCT and optical surface images were analyzed for each patient. The tumor trajectories identified in CBCT projections were used as reference and compared with the target trajectories estimated from surface displacement with the a priori motion model. The resulting absolute differences between the reference and estimated tumor motion along the 2 image dimensions ranged between 0.7 and 2.4 mm; the measured phase shifts did not exceed 7% of the breathing cycle length.Conclusions We investigated a tumor tracking method that integrates breathing motion information provided by the 4-dimensional planning CT with surface imaging at the time of treatment, representing an alternative approach to point-based external-internal correlation models. Although an in-room radiograph-based assessment of the reliability of the motion model is envisaged, the developed technique does not involve the estimation and continuous update of correlation parameters, thus requiring a less intense use of invasive imaging