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

Respiratory-induced organ motion compensation for MRgHIFU

Summary: High Intensity Focused Ultrasound is an emerging non-invasive technology for the precise thermal ablation of pathological tissue deep within the body. The fitful, respiratoryinduced motion of abdominal organs, such as of the liver, renders targeting challenging. The work in hand describes methods for imaging, modelling and managing respiratoryinduced organ motion. The main objective is to enable 3D motion prediction of liver tumours for the treatment with Magnetic Resonance guided High Intensity Focused Ultrasound (MRgHIFU). To model and predict respiratory motion, the liver motion is initially observed in 3D space. Fast acquired 2D magnetic resonance images are retrospectively reconstructed to time-resolved volumes, thus called 4DMRI (3D + time). From these volumes, dense deformation fields describing the motion from time-step to time-step are extracted using an intensity-based non-rigid registration algorithm. 4DMRI sequences of 20 subjects, providing long-term recordings of the variability in liver motion under free breathing, serve as the basis for this study. Based on the obtained motion data, three main types of models were investigated and evaluated in clinically relevant scenarios. In particular, subject-specific motion models, inter-subject population-based motion models and the combination of both are compared in comprehensive studies. The analysis of the prediction experiments showed that statistical models based on Principal Component Analysis are well suited to describe the motion of a single subject as well as of a population of different and unobserved subjects. In order to enable target prediction, the respiratory state of the respective organ was tracked in near-real-time and a temporal prediction of its future position is estimated. The time span provided by the prediction is used to calculate the new target position and to readjust the treatment focus. In addition, novel methods for faster acquisition of subject-specific 3D data based on a manifold learner are presented and compared to the state-of-the art 4DMRI method. The developed methods provide motion compensation techniques for the non-invasive and radiation-free treatment of pathological tissue in moving abdominal organs for MRgHIFU. ---------- Zusammenfassung: High Intensity Focused Ultrasound ist eine aufkommende, nicht-invasive Technologie für die präzise thermische Zerstörung von pathologischem Gewebe im Körper. Die unregelmässige ateminduzierte Bewegung der Unterleibsorgane, wie z.B. im Fall der Leber, macht genaues Zielen anspruchsvoll. Die vorliegende Arbeit beschreibt Verfahren zur Bildgebung, Modellierung und zur Regelung ateminduzierter Organbewegung. Das Hauptziel besteht darin, 3D Zielvorhersagen für die Behandlung von Lebertumoren mittels Magnetic Resonance guided High Intensity Focused Ultrasound (MRgHIFU) zu ermöglichen. Um die Atembewegung modellieren und vorhersagen zu können, wird die Bewegung der Leber zuerst im dreidimensionalen Raum beobachtet. Schnell aufgenommene 2DMagnetresonanz- Bilder wurden dabei rückwirkend zu Volumen mit sowohl guter zeitlicher als auch räumlicher Auflösung, daher 4DMRI (3D + Zeit) genannt, rekonstruiert. Aus diesen Volumen werden Deformationsfelder, welche die Bewegung von Zeitschritt zu Zeitschritt beschreiben, mit einem intensitätsbasierten, nicht-starren Registrierungsalgorithmus extrahiert. 4DMRI-Sequenzen von 20 Probanden, welche Langzeitaufzeichungen von der Variabilität der Leberbewegung beinhalten, dienen als Grundlage für diese Studie. Basierend auf den gewonnenen Bewegungsdaten wurden drei Arten von Modellen in klinisch relevanten Szenarien untersucht und evaluiert. Personen-spezifische Bewegungsmodelle, populationsbasierende Bewegungsmodelle und die Kombination beider wurden in umfassenden Studien verglichen. Die Analyse der Vorhersage-Experimente zeigte, dass statistische Modelle basierend auf Hauptkomponentenanalyse gut geeignet sind, um die Bewegung einer einzelnen Person sowie einer Population von unterschiedlichen und unbeobachteten Personen zu beschreiben. Die Bewegungsvorhersage basiert auf der Abschätzung der Organposition, welche fast in Echtzeit verfolgt wird. Die durch die Vorhersage bereitgestellte Zeitspanne wird verwendet, um die neue Zielposition zu berechnen und den Behandlungsfokus auszurichten. Darüber hinaus werden neue Methoden zur schnelleren Erfassung patienten-spezifischer 3D-Daten und deren Rekonstruktion vorgestellt und mit der gängigen 4DMRI-Methode verglichen. Die entwickelten Methoden beschreiben Techniken zur nichtinvasiven und strahlungsfreien Behandlung von krankhaftem Gewebe in bewegten Unterleibsorganen mittels MRgHIFU

Intraoperative Navigation Systems for Image-Guided Surgery

Recent technological advancements in medical imaging equipment have resulted in a dramatic improvement of image accuracy, now capable of providing useful information previously not available to clinicians. In the surgical context, intraoperative imaging provides a crucial value for the success of the operation. Many nontrivial scientific and technical problems need to be addressed in order to efficiently exploit the different information sources nowadays available in advanced operating rooms. In particular, it is necessary to provide: (i) accurate tracking of surgical instruments, (ii) real-time matching of images from different modalities, and (iii) reliable guidance toward the surgical target. Satisfying all of these requisites is needed to realize effective intraoperative navigation systems for image-guided surgery. Various solutions have been proposed and successfully tested in the field of image navigation systems in the last ten years; nevertheless several problems still arise in most of the applications regarding precision, usability and capabilities of the existing systems. Identifying and solving these issues represents an urgent scientific challenge. This thesis investigates the current state of the art in the field of intraoperative navigation systems, focusing in particular on the challenges related to efficient and effective usage of ultrasound imaging during surgery. The main contribution of this thesis to the state of the art are related to: Techniques for automatic motion compensation and therapy monitoring applied to a novel ultrasound-guided surgical robotic platform in the context of abdominal tumor thermoablation. Novel image-fusion based navigation systems for ultrasound-guided neurosurgery in the context of brain tumor resection, highlighting their applicability as off-line surgical training instruments. The proposed systems, which were designed and developed in the framework of two international research projects, have been tested in real or simulated surgical scenarios, showing promising results toward their application in clinical practice

A focused ultrasound treatment system for moving targets (part I):generic system design and in-silico first-stage evaluation

Background Focused ultrasound (FUS) is entering clinical routine as a treatment option. Currently, no clinically available FUS treatment system features automated respiratory motion compensation. The required quality standards make developing such a system challenging. Methods A novel FUS treatment system with motion compensation is described, developed with the goal of clinical use. The system comprises a clinically available MR device and FUS transducer system. The controller is very generic and could use any suitable MR or FUS device. MR image sequences (echo planar imaging) are acquired for both motion observation and thermometry. Based on anatomical feature tracking, motion predictions are estimated to compensate for processing delays. FUS control parameters are computed repeatedly and sent to the hardware to steer the focus to the (estimated) target position. All involved calculations produce individually known errors, yet their impact on therapy outcome is unclear. This is solved by defining an intuitive quality measure that compares the achieved temperature to the static scenario, resulting in an overall efficiency with respect to temperature rise. To allow for extensive testing of the system over wide ranges of parameters and algorithmic choices, we replace the actual MR and FUS devices by a virtual system. It emulates the hardware and, using numerical simulations of FUS during motion, predicts the local temperature rise in the tissue resulting from the controls it receives. Results With a clinically available monitoring image rate of 6.67 Hz and 20 FUS control updates per second, normal respiratory motion is estimated to be compensable with an estimated efficiency of 80%. This reduces to about 70% for motion scaled by 1.5. Extensive testing (6347 simulated sonications) over wide ranges of parameters shows that the main source of error is the temporal motion prediction. A history-based motion prediction method performs better than a simple linear extrapolator. Conclusions The estimated efficiency of the new treatment system is already suited for clinical applications. The simulation-based in-silico testing as a first-stage validation reduces the efforts of real-world testing. Due to the extensible modular design, the described approach might lead to faster translations from research to clinical practice

Correction of motion-induced susceptibility artifacts and B0 drift during proton resonance frequency shift-based MR thermometry in the pelvis with background field removal methods

Purpose: The linear change of the water proton resonance frequency shift (PRFS) with temperature is used to monitor temperature change based on the temporal dif-ference of image phase. Here, the effect of motion-induced susceptibility artifacts on the phase difference was studied in the context of mild radio frequency hyperthermia in the pelvis.Methods: First, the respiratory-induced field variations were disentangled from di-gestive gas motionin the pelvis. The projection onto dipole fields (PDF) as well as the Laplacian boundary value (LBV) algorithm were applied on the phase difference data to eliminate motion-induced susceptibility artifacts. Both background field re-moval (BFR) algorithms were studied using simulations of susceptibility artifacts, a phantom heating experiment, and volunteer and patient heating data.Results: Respiratory-induced field variations were negligible in the presence of the filled water bolus. Even though LBV and PDF showed comparable results for most data, LBV seemed more robust in our data sets. Some data sets suggested that PDF tends to overestimate the background field, thus removing phase attributed to tem-perature. The BFR methods even corrected for susceptibility variations induced by a subvoxel displacement of the phantom. The method yielded successful artifact cor-rection in 2 out of 4 patient treatment data sets during the entire treat

Generation of treatment plans for Magnetic Resonance guided High Intensity Focused Ultrasound (MRgHIFU) in the liver

In this thesis, the self-scanning method is proposed to handle organ motion. It takes advantage of the perpetual respiratory motion to passively scan the tumor. In other words, we are placing the static focal point of the HIFU into the tumor. The motion caused by breathing shifts the tumor through this focal point. We anticipate at which time point tumor tissue is located under the focal spot and modulate the HIFU intensity based on this information. Once the tumor has been ablated along the self-scanned trajectory, the focal spot is relocated to a different but static position within the body. With this method, we combine the advantages of the gating and the tracking method: a HIFU device with a fixed focus can be used and a high duty cycle is achieved. Moreover, since with the self-scanning approach no lateral steering of the focal spot is required, fewer secondary lobes are generated and position-dependent decay of the focal spot intensity during lateral steering is avoided. However, this comes at the cost of an increased complexity at the planning stage

Doctor of Philosophy

dissertationIt is estimated that in 2016, more than 848,000 new cases of cancer will be diagnosed in men with more than a quarter being prostate cancer and more than 26,000 deaths attributed to this disease. Prostate cancer poses a limited risk when detected at an early stage and treatment of stages II-III has a 5-year survival rate of almost 100%. However, these early-stage cancers can eventually progress and develop into stage IV, dramatically dropping the 5-year survival rate to 28%. Thus, development of a new therapy is needed to fully eliminate these tumors. Combination of heat and chemotherapy improves therapeutic efficacy while allowing for reduced dosing of drugs and limiting side effects. Localized hyperthermia has been used to enhance the delivery of polymer therapeutics to prostate tumors through increased blood flow, vascular permeability, and incorporation of heat shock targeting. This strategy has been shown to increase the delivery and retention of polymer-drug conjugates leading to enhanced efficacy. Although much work has been done using this strategy, the effects of different thermal dosing on polymer accumulation are unknown. The first aim of this research is to examine how altering heating parameters influences polymer tumor accumulation. The hypothesis for this aim is that there is an optimal thermal treatment that leads to the maximal amount of polymer accumulation in the tumors. Additionally, the previously used heating method of plasmonic photothermal therapy (PPTT) can result in long-term accumulation of gold nanoparticles in healthy organs, potentially limiting clinical applicability. The second aim of this proposal will be focused on investigating the alternative method of high intensity focused ultrasound (HIFU) for selective heating of tumors and enhancing macromolecular delivery. HIFU has shown the capability for precise, noninvasive heating of specific regions within the prostate through magnetic resonance imaging (MRI) guidance. The hypothesis to be tested in this aim is that mild hyperthermia produced with HIFU will have the same effect as that produced by PPTT in improving the delivery of macromolecular systems to solid tumors. Finally, in the third aim, the enhanced delivery of targeted polymer therapeutics to prostate tumors in mice models will be investigated using mild hyperthermia produced with HIFU. In the long term, it is anticipated that HIFU can be used in conjunction with delivery of polymer-drug conjugates for enhanced efficacy and reduced toxicity of chemotherapy to produce a clinically relevant treatment of advanced prostate cancer

Design and evaluation of an MRI-compatible linear motion stage.

PURPOSE: To develop and evaluate a tool for accurate, reproducible, and programmable motion control of imaging phantoms for use in motion sensitive magnetic resonance imaging (MRI) appli cations. METHODS: In this paper, the authors introduce a compact linear motion stage that is made of nonmagnetic material and is actuated with an ultrasonic motor. The stage can be positioned at arbitrary positions and orientations inside the scanner bore to move, push, or pull arbitrary phantoms. Using optical trackers, measuring microscopes, and navigators, the accuracy of the stage in motion control was evaluated. Also, the effect of the stage on image signal-to-noise ratio (SNR), artifacts, and B0 field homogeneity was evaluated. RESULTS: The error of the stage in reaching fixed positions was 0.025 ± 0.021 mm. In execution of dynamic motion profiles, the worst-case normalized root mean squared error was below 7% (for frequencies below 0.33 Hz). Experiments demonstrated that the stage did not introduce artifacts nor did it degrade the image SNR. The effect of the stage on the B0 field was less than 2 ppm. CONCLUSIONS: The results of the experiments indicate that the proposed system is MRI-compatible and can create reliable and reproducible motion that may be used for validation and assessment of motion related MRI applications

Doctor of Philosophy

dissertationThis dissertation presents original research that improves the ability of magnetic resonance imaging (MRI) to measure temperature in aqueous tissue using the proton resonance frequency (PRF) shift and T1 measurements in fat tissue in order to monitor focused ultrasound (FUS) treatments. The inherent errors involved in measuring the longitudinal relaxation time T1 using the variable flip angle method with a two-dimensional (2D) acquisition are presented. The edges of the slice profile can contribute a significant amount of signal for large flip angles at steady state, which causes significant errors in the T1 estimate. Only a narrow range of flip angle combinations provided accurate T1 estimates. Respiration motion causes phase artifacts, which lead to errors when measuring temperature changes using the PRF method. A respiration correction method for 3D imaging temperature of the breast is presented. Free induction decay (FID) navigators were used to measure and correct phase offsets induced by respiration. The precision of PRF temperature measurements within the breast was improved by an average factor of 2.1 with final temperature precision of approximately 1 °C. Locating the position of the ultrasound focus in MR coordinates of an ultrasound transducer with multiple degrees of freedom can be difficult. A rapid method for predicting the position using 3 tracker coils with a special MRI pulse iv sequence is presented. The Euclidean transformation of the coil's current positions to their calibration positions was used to predict the current focus position. The focus position was predicted to within approximately 2.1 mm in less than 1 s. MRI typically has tradeoffs between imaging field of view and spatial and temporal resolution. A method for acquiring a large field of view with high spatial and temporal resolution is presented. This method used a multiecho pseudo-golden angle stack of stars imaging sequence to acquire the large field of view with high spatial resolution and k-space weighted image contrast (KWIC) to increase the temporal resolution. The pseudo-golden angle allowed for removal of artifacts introduced by the KWIC reconstruction algorithm. The multiple echoes allowed for high readout bandwidth to reduce blurring due to off resonance and chemical shift as well as provide separate water/fat images, estimates of the initial signal magnitude M(0), T2 * time constant, and combination of echo phases. The combined echo phases provided significant improvement to the PRF temperature precision, and ranged from ~0.3-1.0 °C within human breast. M(0) and T2 * values can possibly be used as a measure of temperature in fat