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

Surrogate-driven respiratory motion models for MRI-guided lung radiotherapy treatments

An MR-Linac integrates an MR scanner with a radiotherapy delivery system, providing non-ionizing real-time imaging of the internal anatomy before, during and after radiotherapy treatments. Due to spatio-temporal limitations of MR imaging, only high-resolution 2D cine-MR images can be acquired in real-time during MRI-guided radiotherapy (MRIgRT) to monitor the respiratory-induced motion of lung tumours and organs-at-risk. However, temporally-resolved 3D anatomical information is essential for accurate MR guidance of beam delivery and dose estimation of the actually delivered dose. Surrogate-driven respiratory motion models can estimate the 3D motion of the internal anatomy from surrogate signals, producing the required information. The overall aim of this thesis was to tailor a generalized respiratory motion modelling framework for lung MRIgRT. This framework can fit the model directly to unsorted 2D MR images sampling the 3D motion, and to surrogate signals extracted from the 2D cine-MR images acquired on an MR-Linac. It can model breath-to-breath variability and produce a motion compensated super-resolution reconstruction (MCSR) 3D image that can be deformed using the estimated motion. In this work novel MRI-derived surrogate signals were generated from 2D cine-MR images to model respiratory motion for lung cancer patients, by applying principal component analysis to the control point displacements obtained from the registration of the cine-MR images. An MR multi-slice interleaved acquisition potentially suitable for the MR-Linac was developed to generate MRI-derived surrogate signals and build accurate respiratory motion models with the generalized framework for lung cancer patients. The developed models and the MCSR images were thoroughly evaluated for lung cancer patients scanned on an MR-Linac. The results showed that respiratory motion models built with the generalized framework and minimal training data generally produced median errors within the MCSR voxel size of 2 mm, throughout the whole 3D thoracic field-of-view and over the expected lung MRIgRT treatment times

Investigation of time-resolved volumetric MRI to enhance MR-guided radiotherapy of moving lung tumors

In photon radiotherapy of lung cancer, respiratory-induced motion introduces systematic and statistical uncertainties in treatment planning and dose delivery. By integrating magnetic resonance imaging (MRI) in the treatment planning process in MR-guided radiotherapy (MRgRT), uncertainties in target volume definition can be reduced with respect to state-of-the-art X-ray-based approaches. Furthermore, MR-guided linear accelerators (MR-Linacs) offer dose delivery with enhanced accuracy and precision through daily treatment plan adaptation and gated beam delivery based on real-time MRI. Today, the potential of MRgRT of moving targets is, however, not fully exploited due to the lack of time-resolved four-dimensional MRI (4D-MRI) in clinical practice. Therefore, the aim of this thesis was to develop and experimentally validate new methods for motion characterization and estimation with 4D-MRI for MRgRT of lung cancer. Different concepts were investigated for all phases of the clinical workflow - treatment planning, beam delivery, and post-treatment analysis. Firstly, a novel internal target volume (ITV) definition method based on the probability-of-presence of moving tumors derived from real-time 4D-MRI was developed. The ability of the ITVs to prospectively account for changes occurring over the course of several weeks was assessed in retrospective geometric analyses of lung cancer patient data. Higher robustness of the probabilistic 4D-MRI-based ITVs against interfractional changes was observed compared to conventional target volumes defined with four-dimensional computed tomography (4D-CT). The study demonstrated that motion characterization over extended times enabled by real-time 4D-MRI can reduce systematic and statistical uncertainties associated with today’s standard workflow. Secondly, experimental validation of a published motion estimation method - the propagation method - was conducted with a porcine lung phantom under realistic patient-like conditions. Estimated 4D-MRIs with a temporal resolution of 3.65 Hz were created based on orthogonal 2D cine MRI acquired at the scanner unit of an MR-Linac. A comparison of these datasets with ground truth respiratory-correlated 4D-MRIs in geometric analyses showed that the propagation method can generate geometrically accurate estimated 4D-MRIs. These could decrease target localization errors and enable 3D motion monitoring during beam delivery at the MR-Linac in the future. Lastly, the propagation method was extended to create continuous time-resolved estimated synthetic CTs (tresCTs). The proposed method was experimentally tested with the porcine lung phantom, successively imaged at a CT scanner and an MR-Linac. A high agreement of the images and corresponding dose distributions of the tresCTs and measured ground truth 4D-CTs was found in geometric and dosimetric analyses. The tresCTs could be used for post-treatment time-resolved reconstruction of the delivered dose to guide treatment adaptations in the future. These studies represent important steps towards a clinical application of time-resolved 4D-MRI methods for enhanced MRgRT of lung tumors in the near future

A framework for continuous target tracking during MR-guided high intensity focused ultrasound thermal ablations in the abdomen

Scatterplot showing percentage changes in stroke volume index (ΔSVI, %) and functional hemodynamic markers, Stroke Volume Variation (SVV, %) Pulse Pressure Variation (PPV, %), with the three tested tidal volumes (V T ), 6, 12 and 18 ml/kg during intra-abdominal hypertension. Solid line shows regression line between variables. (PDF 56 kb

Inter- and Intrafraction Motion Management for MR guided Proton Therapy of Pancreatic Carcinoma

Hintergrund: Patienten mit Bauchspeicheldrüsenkrebs könnten von der Protonentherapie (PT) profitieren, aufgrund ihres Potentials der Schonung von Risikoorganen. Jedoch führen die inter- und intrafraktionelle Beweglichkeit der Bauchspeicheldrüse zu hohen Unsicherheiten bei der Dosisapplikation und erfordern daher große Sicherheitssäume. Aufgrund des hohen Weichgewebskontrastes in der MRT und der Möglichkeit der Echtzeitbildgebung gewinnt die Unterstützung der Strahlentherapie durch die MRT stetig höheres Interesse. In der Translation von konventioneller Röntgen-geführter XT zur MR-geführten PT müssen Methoden zur Kontrolle der inter- und intrafraktionellen Organbeweglichkeit re-evaluiert, adaptiert oder neu entwickelt werden. Fragestellung/Hypothese: Für die interfraktionelle Bewegungskontrolle wurde die Hypothese aufgestellt, dass der neu entwickelte Flüssigmarker BioXmark®, injiziert in Pankreasgewebe, sichtbar in der MR-Bildgebung ist und verglichen zu üblich verwendeten soliden Markern die Bildartefakte reduziert. Für die intrafraktionelle Bewegungskontrolle wurde erwartet, dass ein Patienten-individuelles MR-kompatibles Korsett die atmungs-induzierte Pankreasbeweglichkeit reduziert, von Patienten mit Tumoren im Oberbauch gut vertragen wird und in die PT implementiert werden kann. Ein 4D MR-Linac Bewegungsphantom wurde für die Evaluierung der Geometrietreue und der Genauigkeit der Bewegungswiedergabe des genutzten diagnostischen 3.0 T MR Scanners verwendet. Es wurde erwartet, dass dieses Phantom für die Verwendung am diagnostischen MR Scanner implementiert werden kann und für die Qualitätssicherung von bewegungscharakterisierenden MR Pulssequenzen genutzt werden kann. Material und Methode: Die MR Eigenschaften von BioXmark® wurden in einer Phantomstudie durch MR Relaxometrie quantitativ analysiert und verglichen mit zwei Arten von soliden Marker. Des weiteren wurde die MR-Sichtbarkeit von BioXmark® das erste mal in ex vivo tumorösem Pankreasgewebe getestet für Markern dreier Größenkategorien (20/25 µL, 50/60 µL, 100 µL), injeziert mit jeweils drei verschiedenen Nadelgrößen (18 G, 22 G, 25 G). Ein 4D MR-Linac Bewegungsphantom wurde für den diagnostischen 3.0 T MR Scanner unserer Klinik kommissioniert und Programme für die automatische Evaluierung der 3D Geometrietreue und Genauigkeit der Bewegungscharakterisierung entwickelt. Drei Korsetts aus verschiedenen Materialien (PU, PE, 3DPE) wurden in Bezug auf die Verwendbarkeit in der PT untersucht. Des weiteren wurde der Effekt der Korsetts auf die Reduzierung der Pankreasbeweglichkeit bei einem gesunden Freiwilligen analysiert, mittels zeitaufgelöster 2D-cine MRT und respirationskorrelierter 4D-MRT in einem 1.5 T MR Scanner. Daraufhin wurde eine klinische Studie durchgeführt, die 13 Patienten mit Tumor im Oberbauch einschloss. Im Rahmen der Studie wurde der Effekt des verwendeten 3DPE Korsetts auf die Reduktion der Pankreasbeweglichkeit analysiert, mittels 2D-cine MRT und 4D-MRT in einem 3.0 T MR Scanner. Abschließend wurde die Patienten-Verträglichkeit bei Anwendung des Korsetts analysiert. Ergebnisse: Für BioXmark® wurde keine Korrelation zwischen der Intensität der Sichtbarkeit und Artefakte gefunden (RS = 0.0) und nur eine schwache Korrelation zwischen der Größe der Sichtbarkeit und Artefakte (RS = 0.4). Im Gegensatz dazu wurde für die soliden Marker eine lineare Abhängigkeit der Größe der Sichtbarkeit und Artefakte (RS = 0.99) und eine nicht-lineare Abhängigkeit zwischen der Intensität der Sichtbarkeit und Artefakte gefunden (RS = 0.964). Nach Injektion in drei ex vivo Pankreas-Resektionspräparate war BioXmark® als Hypointensität in sowohl T1- als auch T2- gewichteten MR Bildgebung sichtbar. Marker aller drei getesteten Größenkategorien waren in klinisch verwendeten MR Sequenzen detektierbar. Jedoch führte eine diffuse Gelierung oder Injektion zu nah am Geweberand zur Minderung der Detektierbarkeit. Dies hatte zur Folge hatte, dass 4 von in Summe 17 Markern in der MR-Bildgebung nicht erkennbar waren. Das MR-Linac Bewegungsphantom wurde erfolgreich am diagnostischen 3.0 T MR Scanner kommissioniert. Eine Fixierungs- und Positionierungshilfe wurde entwickelt und konstruiert, die eine sichere und reproduzierbare Positionierung des Aktuators und des Phantoms (< 0.4mm) ermöglichte. Ein Programm zur automatischen Verzerrungsanalyse wurde entwickelt, basierend auf einer Referenz-CT Aufnahme. Die Auswertung einer klinisch verwendeten 3D GRE Sequenz offenbarte eine maximale Verzerrung von 1.3mm in einem elliptischen Zylindervolumen von 15×23×6 cm³. Das Referenz-CT offenbarte zusätzlich einen Abweichung der eingestellten Targetbeweglichkeit in AP/LR Richtung. Kontrastreiche und geometrisch korrekte 2D-cine MR Bilder des sich bewegenden Phantom-Targets konnten aufgenommen werden. Ein Programm für ein automatisiertes Target-Tracking wurde entwickelt, welches eine hohe Genauigkeit der bewegungscharakterisierenden Sequenzen bestätigte (< 0.2mm in 2D-cine MRT, < 0.3mm in 4D-MRT). Eine vergleichbare Reduzierung der respirationsbedingten Pankreas-Bewegung von 46%–56% (7.7mm – 9.4 mm) wurde für die drei getesteten Korsetts gefunden. Die Materialanalyse führte jedoch zum Ausschluss des PU Korsetts für die Verwendung in der PT, aufgrund der gravierenden Heterogenität des Korsettmaterials. Das 3DPE Korsett wurde als für die PT implementierbar bewertet, wobei eine direkte Integration in der PT Planung mit der klinisch verwendeten Hounsfield-SPR Übersetzungstabelle möglich war. Das 3DPE Korsett wurde für 13 Patienten mit Tumor im Oberbauch in den PT Arbeitsablauf integriert, in welchem das Korsett von den Patienten gut toleriert wurde. Die MR-basierte Analyse der respirationsbedingten Pankreasbewegung in 9 Patienten mit und ohne Korsett ergab eine Reduzierung der Beweglichkeit um 37% (~3.3 mm). Schlussfolgerungen: BioXmark® und das entwickelte 3DPE Korsett wurden als verwendbar für die MR geführte PT bewertet. BioXmark® war in der MR-Bildgebung als Hypointensität sichtbar, unabhängig von der verwendeten MR Pulssequenz, solange die Markergröße die Voxelauflösung überschritt. Die MR-Sichtbarkeit von BioXmark® sollte jedoch in vivo getestet werden, da sich dort die Gelierung unterscheiden könnte und dementsprechend die Sichtbarkeit beeinflussen könnte. Das MR-Linac Bewegungsphantom kann in Zukunft für QA von bewegungscharakterisierenden Pulssequenzen des diagnostischen MR Scanners verwendet werden. Dies ist empfohlen, wann immer neue Pulssequenzen implementiert werden. Das entwickelte Korsett reduziert die respirationsbedingte Pankreas-Beweglichkeit in Patienten mit Tumor im Oberbauch um ~37% und kann in Zukunft für die MR geführte PT verwendet werden. Die Studie offenbarte jedoch auch, dass eine erhebliche Anzahl an Patienten nicht von der Verwendung eines Korsetts profitiert, aufgrund ihrer initial geringen Beweglichkeit bei freier Atmung (< 6 mm). Schlussfolgernd ist eine vorherige Einschätzung der Beweglichkeit jedes individuellen Patienten bei freier Atmung zu empfehlen, bevor eine Entscheidung über die Implementierung des Korsetts in der PT getroffen wird

Magnetic resonance imaging of lung cancer in the presence of respiratory motion: Dynamic keyhole and audio visual biofeedback

Breath-to-breath variations in breathing can cause image artefacts. Day-to-day variations can cause a disagreement of position and volume between planning and treatment throughout radiotherapy procedures, requiring a larger treatment margin and longer treatment time. An advanced radiotherapy system requires: (1) a fast imaging technique for the compensation of breathing variations and/or (2) a respiratory motion management technique for the control of breathing variations. A novel MRI reconstruction method called “Dynamic keyhole” was proposed as a fast imaging technique. This thesis investigated (1) the concept of this method in terms of the improvement in temporal resolution with healthy volunteer MRI datasets and (2) the applicability of real-time lung tumour localization in terms of the accuracy of tumour motion and shape with lung cancer patient MRI datasets. The dynamic keyhole method achieved an increase in imaging frequency by up to a factor of five when compared with full k-space methods whilst achieving sub-millimetre tumour motion accuracy and preserving tumour shape within 98%. AV biofeedback respiratory guidance was used for healthy volunteers and lung cancer patients. This thesis investigated the impact of AV biofeedback on (1) intra- and inter-fraction lung tumour motion using cine-MRI, (2) inter-fraction lung tumour position and intra-fraction tumour volume using breath-hold MRI and (3) the improvement in image quality and the reduction in scan time using respiratory-gated MRI. AV biofeedback respiratory guidance improved intra- and inter-fraction tumour motion and position reproducibility, and intra-fraction tumour volume consistency. In addition, it was found to improve image quality and reduce scan time. The performance of the dynamic keyhole method and AV biofeedback respiratory guidance shown in this thesis illustrates potential advantages of real-time tumour imaging and tumour motion management in the course of lung cancer radiotherapy

Autoadaptive motion modelling for MR-based respiratory motion estimation

© 2016 The Authors.Respiratory motion poses significant challenges in image-guided interventions. In emerging treatments such as MR-guided HIFU or MR-guided radiotherapy, it may cause significant misalignments between interventional road maps obtained pre-procedure and the anatomy during the treatment, and may affect intra-procedural imaging such as MR-thermometry. Patient specific respiratory motion models provide a solution to this problem. They establish a correspondence between the patient motion and simpler surrogate data which can be acquired easily during the treatment. Patient motion can then be estimated during the treatment by acquiring only the simpler surrogate data.In the majority of classical motion modelling approaches once the correspondence between the surrogate data and the patient motion is established it cannot be changed unless the model is recalibrated. However, breathing patterns are known to significantly change in the time frame of MR-guided interventions. Thus, the classical motion modelling approach may yield inaccurate motion estimations when the relation between the motion and the surrogate data changes over the duration of the treatment and frequent recalibration may not be feasible.We propose a novel methodology for motion modelling which has the ability to automatically adapt to new breathing patterns. This is achieved by choosing the surrogate data in such a way that it can be used to estimate the current motion in 3D as well as to update the motion model. In particular, in this work, we use 2D MR slices from different slice positions to build as well as to apply the motion model. We implemented such an autoadaptive motion model by extending our previous work on manifold alignment.We demonstrate a proof-of-principle of the proposed technique on cardiac gated data of the thorax and evaluate its adaptive behaviour on realistic synthetic data containing two breathing types generated from 6 volunteers, and real data from 4 volunteers. On synthetic data the autoadaptive motion model yielded 21.45% more accurate motion estimations compared to a non-adaptive motion model 10 min after a change in breathing pattern. On real data we demonstrated the methods ability to maintain motion estimation accuracy despite a drift in the respiratory baseline. Due to the cardiac gating of the imaging data, the method is currently limited to one update per heart beat and the calibration requires approximately 12 min of scanning. Furthermore, the method has a prediction latency of 800 ms. These limitations may be overcome in future work by altering the acquisition protocol

Advanced H-1 Lung Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) is one of the widely used medical imaging modality, since it can provide both structural and functional assessment in a single imaging session. However, two major challenges should be considered by using MRI for lung imaging. The first challenge is the intrinsic low SNR of H-1 lung MRI due to the low proton density as well as the fast decay of the lung parenchyma signal. And the second challenge is subject motion. To achieve high resolution structural image, MRI requires a long scan time, usually a few minutes or even longer, which make MRI sensitive to subject motion. To address the first challenge, ultra-short echo time (UTE) MRI sequence is used to capture the lung parenchyma signal before decay. As for subject motion, two major strategies are widely used. One strategy is fast breath-holding scan, the subjects are asked to hold their breaths for a short duration, and the fast 3D MR sequence would be used to acquire data within that duration. This dissertation proposes a new acquisition scheme based on the standard UTE sequence, which largely increases the encoding efficiency and improves the breath-holding scan images. The other is free breathing scan with motion correction. The subjects are allowed to breathe during the MR acquisition. After the acquisition, the motion corrupted data would go through the motion correction step to reconstruct the motion free images. In this dissertation, two novel motion corrected reconstruction strategies are proposed to incorporate the motion modeling and compensation into the reconstruction to get high SNR motion corrected 3D and 4D images. When translating the developed techniques to the clinical studies, specifically for pediatric and neonatal studies, more practical problems need to be considered, such as smaller but finer anatomy to image, the different respiratory patterns of the young subjects etc. This dissertation proposes a 5-minute free breathing UTE MRI strategy to achieve a 3D high resolution motion free lung image for pediatric and neonatal studies

Efficient deformable motion correction for 3-D abdominal MRI using manifold regression

We present a novel framework for efficient retrospective respiratory motion correction of 3-D abdominal MRI using manifold regression. K-space data are continuously acquired under free breathing using the stack-of-stars radial gold-en-angle trajectory. The stack-of-profiles (SoP) from all temporal positions are embedded into a common manifold, in which SoPs that were acquired at similar respiratory states are close together. Next, the SoPs in the manifold are clustered into groups using the k-means algorithm. One 3-D volume is reconstructed at the central SoP position of each cluster (a.k.a. key-volumes). Motion fields are estimated using deformable image registration between each of these key-volumes and a reference end-exhale volume. Subsequently, the motion field at any other SoP position in the manifold is derived using manifold regression. The regressed motion fields for each of the SoPs are used to deter-mine a final motion-corrected MRI volume. The method was evaluated on realistic synthetic datasets which were generated from real MRI data and also tested on an in vivo dataset. The framework enables more accurate motion correction compared to the conventional binning-based approach, with high computational efficiency