Respiratory organ motion in interventional MRI : tracking, guiding and modeling

Respiratory organ motion is one of the major challenges in interventional MRI, particularly in interventions with therapeutic ultrasound in the abdominal region. High-intensity focused ultrasound found an application in interventional MRI for noninvasive treatments of different abnormalities. In order to guide surgical and treatment interventions, organ motion imaging and modeling is commonly required before a treatment start. Accurate tracking of organ motion during various interventional MRI procedures is prerequisite for a successful outcome and safe therapy. In this thesis, an attempt has been made to develop approaches using focused ultrasound which could be used in future clinically for the treatment of abdominal organs, such as the liver and the kidney. Two distinct methods have been presented with its ex vivo and in vivo treatment results. In the first method, an MR-based pencil-beam navigator has been used to track organ motion and provide the motion information for acoustic focal point steering, while in the second approach a hybrid imaging using both ultrasound and magnetic resonance imaging was combined for advanced guiding capabilities. Organ motion modeling and four-dimensional imaging of organ motion is increasingly required before the surgical interventions. However, due to the current safety limitations and hardware restrictions, the MR acquisition of a time-resolved sequence of volumetric images is not possible with high temporal and spatial resolution. A novel multislice acquisition scheme that is based on a two-dimensional navigator, instead of a commonly used pencil-beam navigator, was devised to acquire the data slices and the corresponding navigator simultaneously using a CAIPIRINHA parallel imaging method. The acquisition duration for four-dimensional dataset sampling is reduced compared to the existing approaches, while the image contrast and quality are improved as well. Tracking respiratory organ motion is required in interventional procedures and during MR imaging of moving organs. An MR-based navigator is commonly used, however, it is usually associated with image artifacts, such as signal voids. Spectrally selective navigators can come in handy in cases where the imaging organ is surrounding with an adipose tissue, because it can provide an indirect measure of organ motion. A novel spectrally selective navigator based on a crossed-pair navigator has been developed. Experiments show the advantages of the application of this novel navigator for the volumetric imaging of the liver in vivo, where this navigator was used to gate the gradient-recalled echo sequence

4D-CT Lung Registration and its Application for Lung Radiation Therapy

Radiation therapy has been successful in treating lung cancer patients, but its efficacy is limited by the inability to account for the respiratory motion during treatment planning and radiation dose delivery. Physics-based lung deformation models facilitate the motion computation of both tumor and local lung tissue during radiation therapy. In this dissertation, a novel method is discussed to accurately register 3D lungs across the respiratory phases from 4D-CT datasets, which facilitates the estimation of the volumetric lung deformation models. This method uses multi-level and multi-resolution optical flow registration coupled with thin plate splines (TPS), to address registration issue of inconsistent intensity across respiratory phases. It achieves higher accuracy as compared to multi-resolution optical flow registration and other commonly used registration methods. Results of validation show that the lung registration is computed with 3 mm Target Registration Error (TRE) and approximately 3 mm Inverse Consistency Error (ICE). This registration method is further implemented in GPU based real time dose delivery simulation to assist radiation therapy planning

In-house Implementation and Validation of the Mid-Position CT approach for the Treatment Planning of Respiration-induced Moving Tumours in Radiotherapy for Lung and Upper abdomen cancer

Tese mestrado integrado, Engenharia Biomédica e Biofísica (Engenharia Clínica e Instrumentação Médica) Universidade de Lisboa, Faculdade de Ciências, 2022A Radioterapia é uma das modalidades principais para tratamentos de foro oncológico que visa destruir a ação proliferativa das células cancerígenas e reduzir o volume tumoral. A sua ação terapêutica através do uso de radiação ionizante tem, subjacente, a máxima de irradiar o tumor com uma elevada dose, ao mesmo tempo que os órgãos de risco (OARs) adjacentes, são tanto quanto possível protegidos. Quando um tumor se localiza no pulmão ou abdómen superior, como no fígado ou pâncreas, o seu movimento devido à respiração pode alcançar até 4 cm, especialmente na direção crânio-caudal, aumentando as incertezas relativas à posição do tumor. No Centro Clínico Champalimaud (CCC), o planeamento convencional dos tratamentos de radioterapia faz uso de uma tomografia computadorizada (CT) que é adquirida aquando da respiração livre do doente e que, por isso, apresenta geralmente artefactos que podem ser uma fonte de erro durante o planeamento. Nos casos em que o movimento do tumor é considerável, é ainda adquirida uma tomografia computadorizada quadrimensional (4DCT) que consiste entre 8 e 10 CTs que representam fases do ciclo respiratório. Posteriormente, a 4DCT é utilizada para delinear o volume interno do alvo (ITV) que engloba toda a extensão do movimento do tumor. Apesar da estratégia do ITV garantir uma adequada cobertura do volume-alvo, os OARs ficam expostos a doses de radiação desnecessárias e a um maior risco de toxicidade. Este efeito é ainda mais preocupante em tratamentos hipofracionados, onde doses mais elevadas são administradas num número reduzido de frações. Nos últimos anos têm sido desenvolvidas estratégias que visam tornar os tratamentos de radioterapia mais eficazes. Uma delas é a reconstrução de uma CT que representa a posição média do doente ao longo do ciclo respiratório (Mid-P CT). Esta estratégia resulta em volumes de tratamento menores do que a estratégia do ITV, possibilitando o aumento da dose e maior controlo tumoral local. O primeiro passo para a reconstrução do Mid-P CT é o registo deformável de imagens (DIR) entre uma das fases da respiração (uma CT da 4DCT), definida como a fase de referência, e as restantes fases. Deste processo resultam campos vetoriais deformáveis (DVF) que contém informação do deslocamento dos tecidos. Os DVFs são subsequentemente utilizados para transformar cada uma das fases da respiração para a posição média. O método do Mid-P foi implementado com sucesso no Instituto do Cancro Holandês (NKI) em 2008. Apesar dos bons resultados clínicos, o número de centros de radioterapia que utiliza esta técnica é muito reduzido. Tal deve-se, por um lado, à inexistência de soluções comerciais com esta funcionalidade e, por outro, ao esforço necessário alocar para implementar e validar soluções desenvolvidas internamente. O presente projeto teve como principal objetivo implementar a estratégia do Mid-P no CCC (Portugal). Para tal, foi otimizado um módulo – RunMidP – desenvolvido para o software 3D Slicer, que calcula o Mid-P CT e estima a amplitude do movimento do tumor e OARs com base nos DVFs. Considerando que a precisão do módulo e a qualidade de imagem do Mid-P CT devem atender os requisitos para o planeamento em radioterapia, foram realizados testes para validar o módulo. Sempre que possível, a sua performance foi comparada com outras aplicações desenvolvidas para a implementação da técnica do Mid-P, nomeadamente com um protótipo desenvolvido pela empresa Mirada Medical Ltd. (Reino Unido) – Mirada – e com o software desenvolvido no NKI (Holanda) – Wimp. Os testes foram divididos em três estudos diferentes, cada um com um conjunto de dados diferente. No primeiro estudo (estudo A), foram utilizadas 4DCT de 2 fantomas digitais, cuja função respiratória e cardíaca foi modelada de forma simplificada, e de 18 doentes com tumores localizados no pulmão (N = 8), no fígado (N = 6) e no pâncreas (N = 4). Neste estudo, foram comparados dois algoritmos DIR disponíveis no software 3D Slicer, o Plastimatch e o Elastix, em termos da precisão do registo e da qualidade de imagem do Mid-P CT reconstruído. Foi ainda avaliado a capacidade dos softwares RunMidP e Mirada representarem corretamente a posição média do doente e as diferenças das amplitudes do movimento do tumor estimadas pelos dois softwares. No estudo B, foram realizados testes de verificação semelhantes aos supre mencionados, em imagens sintéticas provenientes de 16 doentes, desta vez com a vantagem de se conhecer o “verdadeiro” Mid-P CT e as “verdadeiras” amplitudes do movimento do tumor. Estes foram comparados com os resultados obtidos com os softwares RunMidP e Mirada. Ainda, as unidades de Hounsfield (HU) no Mid-P CT reconstruído por RunMidP e Mirada foram comparadas com as HU na fase de referência, de modo a verificar se os Mid P CTs produziriam diferenças dosimétricas relevantes. No último estudo (estudo C), a qualidade de imagem do Mid-P CT foi avaliada quantitativamente e qualitativamente. Durante a análise qualitativa, foi pedido a dois médicos especialistas que avaliassem a viabilidade dos Mid-P CTs, reconstruídos pelos três softwares (RunMidP, Mirada e Wimp), para o planeamento dos tratamentos. O tempo da reconstrução do Mid-P CT a partir da 4DCT foi de cerca de 1h. Ambos os algoritmos, Plastimach e Elastix, demonstraram ser adequados para DIR de imagens do pulmão e abdómen superior, com diferenças estatisticamente não significativas (p > 0.05) em termos da precisão do registo. Contudo, o Mid-P CT reconstruído com Elastix apresentou uma melhoria na qualidade de imagem, sendo assim o algoritmo DIR escolhido para ser implementado no RunMidP. Em termos de métricas aplicadas a contornos definidos manualmente, tais como a distância de Hausdorf (HD) e coeficiente de Dice (DSC), o erro do registo de imagem foi menor que 1 mm, dentro do contorno do tumor, e 2 mm no pulmão. Os Mid-P CTs reconstruídos com o RunMidP e Mirada apresentaram maiores diferenças, relativamente ao “verdadeiro” Mid-P CT, na região do diafragma e zonas de maior homogeneidade como, por exemplo, no ar presente no intestino. Contudo, para a maioria dos doentes do estudo B, o Mid-P CT reconstruído com o software Mirada apresentou maior índice de similaridade estrutural (SSIM) relativamente ao “verdadeiro” Mid-P CT. Estes resultados podem estar na origem do uso de diferentes algoritmos DIR, mas deveram-se principalmente a uma falha na aplicação das transformações deformáveis pelo módulo RunMiP que foi corrigida posteriormente. Ainda, as diferenças entre as amplitudes estimadas e previstas foram menores que 1 mm para 37 tumores (78,9%), que resultam em diferenças menores que 0.3mm quando convertidas em margens de planeamento. Para além disso, as diferenças nos valores de HU dos Mid-P CTs comparativamente à fase de referência foram, em média, de 1 HU no tumor e OARs. Foram também observadas melhorias na qualidade de imagem do Mid-P CT, nomeadamente um aumento da relação sinal-ruído (SNR) e diminuição dos artefactos. Estes resultados estão de acordo com a avaliação dos médicos que, em geral, consideraram que os Mid-P CTs reconstruídos pelos três softwares são adequados para o planeamento dos tratamentos. No entanto, os Mid-P CTs reconstruídos com dados 4DCT provenientes do CCC apresentaram classificações inferiores aos reconstruídos com dados 4DCT do NKI. Em suma, as modificações do algoritmo DIR Plastimach para Elastix e a correção do método para aplicar as transformações deformáveis, permitiram uma melhoria na qualidade de imagem do Mid P CT e melhor performance do algoritmo, respetivamente. O módulo RunMidP, neste projeto otimizado e validado, apresenta um forte potencial para a reconstrução e implementação da estratégia do Mid-P na clínica, com performance comparável a outras aplicações existentes (Mirada e Wimp). Atenção especial deve ser dada aos dados 4DCT de input que parecem afetar a qualidade de imagem final do Mid-P CT. No futuro, valerá a pena otimizar os parâmetros de aquisição e reconstrução da 4DCT de modo a melhorar a qualidade de imagem e, ainda, o módulo RunMidP pode potencialmente ser otimizado no que respeita ao tempo de reconstrução do Mid-P CT e à precisão do DIR.Radiotherapy for tumours in the thorax and upper abdomen is challenging since they move notably with breathing. To cover the whole extent of tumour motion, relatively large margins are added to treatment volumes, posing a higher risk of toxicity for surrounding organs-at-risk (OARs). The Mid Position (Mid-P) method accounts for breathing motion by using deformable image registration (DIR) to transform all phases of a 4DCT scan to a time-weighted average 3DCT scan (Mid-P CT). The Mid-P strategy results in smaller treatment volumes, potentially boosting the delivery of hypofractionated treatments. To bring the Mid-P approach to the Champalimaud Clinical Centre (CCC), an in-house Mid position software module – RunMidP – was optimized. The module reconstructs the Mid-P CT and estimates breathing motion amplitudes of tumours and relevant OARs. In addition, this project presents a set of experiments to evaluate the performance of the Mid-P method and its feasibility for clinical implementation. The experiments were conducted throughout three different studies using 4DCT data from 18 phantoms and 23 patients. In Study A, the accuracy and image quality of two DIR algorithms (Plastimatch and Elastix) were assessed using quantitative metrics applied on either warped images or manually delineated contours. The reproduction of the patient’s mean position by the Mid-P CT and the estimation of motion amplitudes were compared to a soon-to-be Mid-P commercial software developed by Mirada Medical Ltd. In Study B,similar experiments were performed, this time using a more rigorous reference – “true” Mid-P CT scans and “true” motion estimations. In Study C, the image quality of Mid P CT scans was assessed quantitatively and qualitatively. Both Plastimatch and Elastix registration showed comparable registration accuracy, although Elastix showed superior image quality of reconstructed Mid-P CTs. Based on contour metrics, the registration error was less than 2 mm. In-house Mid-P CTs showed a slightly lower match to ground truth Mid-P CTs than the ones reconstructed by the Mirada prototype due to differences in DIR methods and small shifts to the original image geometry. Higher image differences were found in the diaphragm lung interface, where the patient's anatomy moves faster due to breathing, and in homogeneous regions such as the air regions in the bowel. On the other hand, differences (estimated-predicted) in motion amplitudes smaller than 1 mm were observed in 37 moving tumours (78.7%), showing a good performance of the Mid-P algorithm. Regarding the image quality, improvements in the signal-to-noise ratio and removal of image artefacts in Mid-P CTs are great advantages for using them as the planning CT. Clinicians also gave a good assessment of the suitability of Mid-P CT scans for treatment planning. No significant differences were found in the performance of the RunMidP compared to other Mid-Position packages, although worse scores were given to the CCC dataset than the dataset from another hospital. The in-house Mid-position algorithm shows promising results regarding the use of the software module in radiotherapy for lung and upper abdomen cancer. Further exploration must be given to improve the registration accuracy, image quality of the input data, and speed up the reconstruction of the Mid-P CT scan

Synthesis of Realistic Simultaneous Positron Emission Tomography and Magnetic Resonance Imaging Data

The investigation of the performance of different positron emission tomography (PET) reconstruction and motion compensation methods requires accurate and realistic representation of the anatomy and motion trajectories as observed in real subjects during acquisitions. The generation of well-controlled clinical datasets is difficult due to the many different clinical protocols, scanner specifications, patient sizes, and physiological variations. Alternatively, computational phantoms can be used to generate large data sets for different disease states, providing a ground truth. Several studies use registration of dynamic images to derive voxel deformations to create moving computational phantoms. These phantoms together with simulation software generate raw data. This paper proposes a method for the synthesis of dynamic PET data using a fast analytic method. This is achieved by incorporating realistic models of respiratory motion into a numerical phantom to generate datasets with continuous and variable motion with magnetic resonance imaging (MRI)-derived motion modeling and high resolution MRI images. In this paper, data sets for two different clinical traces are presented, ¹⁸F-FDG and ⁶⁸Ga-PSMA. This approach incorporates realistic models of respiratory motion to generate temporally and spatially correlated MRI and PET data sets, as those expected to be obtained from simultaneous PET-MRI acquisitions

Breathing adapted radiotherapy: a 4D gating software for lung cancer

<p>Abstract</p> <p>Purpose</p> <p>Physiological respiratory motion of tumors growing in the lung can be corrected with respiratory gating when treated with radiotherapy (RT). The optimal respiratory phase for beam-on may be assessed with a respiratory phase optimizer (RPO), a 4D image processing software developed with this purpose.</p> <p>Methods and Materials</p> <p>Fourteen patients with lung cancer were included in the study. Every patient underwent a 4D-CT providing ten datasets of ten phases of the respiratory cycle (0-100% of the cycle). We defined two morphological parameters for comparison of 4D-CT images in different respiratory phases: tumor-volume to lung-volume ratio and tumor-to-spinal cord distance. The RPO automatized the calculations (200 per patient) of these parameters for each phase of the respiratory cycle allowing to determine the optimal interval for RT.</p> <p>Results</p> <p>Lower lobe lung tumors not attached to the diaphragm presented with the largest motion with breathing. Maximum inspiration was considered the optimal phase for treatment in 4 patients (28.6%). In 7 patients (50%), however, the RPO showed a most favorable volumetric and spatial configuration in phases other than maximum inspiration. In 2 cases (14.4%) the RPO showed no benefit from gating. This tool was not conclusive in only one case.</p> <p>Conclusions</p> <p>The RPO software presented in this study can help to determine the optimal respiratory phase for gated RT based on a few simple morphological parameters. Easy to apply in daily routine, it may be a useful tool for selecting patients who might benefit from breathing adapted RT.</p

Optimizing Respiratory Gated Intensity Modulated Radiation Therapy Planning and Delivery of Early-Stage Non-Small Cell Lung Cancer

Stereotactic ablative body radiotherapy (SABR) is the standard of care for inoperable early-stage non-small cell lung cancer (NSCLC) patients. However, thoracic tumours are susceptible to respiratory motion and, if unaccounted for, can potentially lead to dosimetric uncertainties. Respiratory gating is one method that limits treatment delivery to portions of the respiratory cycle, but when combined with intensity-modulated radiotherapy (IMRT), requires rigorous verification. The goal of this thesis is to optimize respiratory gated IMRT treatment planning and develop image-guided strategies to verify the dose delivery for future early-stage NSCLC patients. Retrospective treatment plans were generated for various IMRT delivery techniques, including fixed-beam, volumetric modulated arc therapy (VMAT), and helical tomotherapy. VMAT was determined the best technique for optimizing dose conformity and efficiency. A second treatment planning study that considered patients exhibiting significant tumour motion was conducted. Respiratory ungated and gated VMAT plans were compared. Significant decreases in V20Gy and V50%, predictors for radiation pneumonitis and irreversible fibrosis, respectively, were observed. The predominant uncertainty of respiratory gating lies in the ability of an external surrogate marker to accurately predict internal target motion. Intrafraction triggered kV imaging was validated in a programmable motion phantom study as a method to determine how correlated the internal and external motion are during ungated and gated VMAT deliveries and to identify potential phase shifts between the motions. KV projections acquired during gated VMAT delivery were used to reconstruct gated cone-beam CT (CBCT), providing 3D tumour position verification. Image quality and target detectability, in the presence of MV scatter from the treatment beam to the kV detector, was evaluated with various imaging parameters and under real-patient breathing motion conditions. No significant difference in image quality was observed for the CBCT acquisitions with or without the presence of MV scatter. This thesis explores the benefits of combining respiratory gating with IMRT/VMAT for the treatment of early stage NSCLC with SABR, and evaluates advanced on-board imaging capabilities to develop dose delivery verification protocols. The results of this thesis will provide the tools necessary to confidently implement a respiratory gated radiotherapy program aimed at improving the therapeutic ratio for early-stage NSCLC