On the Real-Time Performance, Robustness and Accuracy of Medical Image Non-Rigid Registration

Three critical issues about medical image non-rigid registration are performance, robustness and accuracy. A registration method, which is capable of responding timely with an accurate alignment, robust against the variation of the image intensity and the missing data, is desirable for its clinical use. This work addresses all three of these issues. Unacceptable execution time of Non-rigid registration (NRR) often presents a major obstacle to its routine clinical use. We present a hybrid data partitioning method to parallelize a NRR method on a cooperative architecture, which enables us to get closer to the goal: accelerating using architecture rather than designing a parallel algorithm from scratch. to further accelerate the performance for the GPU part, a GPU optimization tool is provided to automatically optimize GPU execution configuration.;Missing data and variation of the intensity are two severe challenges for the robustness of the registration method. A novel point-based NRR method is presented to resolve mapping function (deformation field) with the point correspondence missing. The novelty of this method lies in incorporating a finite element biomechanical model into an Expectation and Maximization (EM) framework to resolve the correspondence and mapping function simultaneously. This method is extended to deal with the deformation induced by tumor resection, which imposes another challenge, i.e. incomplete intra-operative MRI. The registration is formulated as a three variable (Correspondence, Deformation Field, and Resection Region) functional minimization problem and resolved by a Nested Expectation and Maximization framework. The experimental results show the effectiveness of this method in correcting the deformation in the vicinity of the tumor. to deal with the variation of the intensity, two different methods are developed depending on the specific application. For the mono-modality registration on delayed enhanced cardiac MRI and cine MRI, a hybrid registration method is designed by unifying both intensity- and feature point-based metrics into one cost function. The experiment on the moving propagation of suspicious myocardial infarction shows effectiveness of this hybrid method. For the multi-modality registration on MRI and CT, a Mutual Information (MI)-based NRR is developed by modeling the underlying deformation as a Free-Form Deformation (FFD). MI is sensitive to the variation of the intensity due to equidistant bins. We overcome this disadvantage by designing a Top-to-Down K-means clustering method to naturally group similar intensities into one bin. The experiment shows this method can increase the accuracy of the MI-based registration.;In image registration, a finite element biomechanical model is usually employed to simulate the underlying movement of the soft tissue. We develop a multi-tissue mesh generation method to build a heterogeneous biomechanical model to realistically simulate the underlying movement of the brain. We focus on the following four critical mesh properties: tissue-dependent resolution, fidelity to tissue boundaries, smoothness of mesh surfaces, and element quality. Each mesh property can be controlled on a tissue level. The experiments on comparing the homogeneous model with the heterogeneous model demonstrate the effectiveness of the heterogeneous model in improving the registration accuracy

Methodology for Jointly Assessing Myocardial Infarct Extent and Regional Contraction in 3-D CMRI

Automated extraction of quantitative parameters from Cardiac Magnetic Resonance Images (CMRI) is crucial for the management of patients with myocardial infarct. This work proposes a post-processing procedure to jointly analyze Cine and Delayed-Enhanced (DE) acquisitions in order to provide an automatic quantification of myocardial contraction and enhancement parameters and a study of their relationship. For that purpose, the following processes are performed: 1) DE/Cine temporal synchronization and 3D scan alignment, 2) 3D DE/Cine rigid registration in a region about the heart, 3) segmentation of the myocardium on Cine MRI and superimposition of the epicardial and endocardial contours on the DE images, 4) quantification of the Myocardial Infarct Extent (MIE), 5) study of the regional contractile function using a new index, the Amplitude to Time Ratio (ATR). The whole procedure was applied to 10 patients with clinically proven myocardial infarction. The comparison between the MIE and the visually assessed regional function scores demonstrated that the MIE is highly related to the severity of the wall motion abnormality. In addition, it was shown that the newly developed regional myocardial contraction parameter (ATR) decreases significantly in delayed enhanced regions. This largely automated approach enables a combined study of regional MIE and left ventricular function

On motion in dynamic magnetic resonance imaging: Applications in cardiac function and abdominal diffusion

La imagen por resonancia magnética (MRI), hoy en día, representa una potente herramienta para el diagnóstico clínico debido a su flexibilidad y sensibilidad a un amplio rango de propiedades del tejido. Sus principales ventajas son su sobresaliente versatilidad y su capacidad para proporcionar alto contraste entre tejidos blandos. Gracias a esa versatilidad, la MRI se puede emplear para observar diferentes fenómenos físicos dentro del cuerpo humano combinando distintos tipos de pulsos dentro de la secuencia. Esto ha permitido crear distintas modalidades con múltiples aplicaciones tanto biológicas como clínicas. La adquisición de MR es, sin embargo, un proceso lento, lo que conlleva una solución de compromiso entre resolución y tiempo de adquisición (Lima da Cruz, 2016; Royuela-del Val, 2017). Debido a esto, la presencia de movimiento fisiológico durante la adquisición puede conllevar una grave degradación de la calidad de imagen, así como un incremento del tiempo de adquisición, aumentando así tambien la incomodidad del paciente. Esta limitación práctica representa un gran obstáculo para la viabilidad clínica de la MRI. En esta Tesis Doctoral se abordan dos problemas de interés en el campo de la MRI en los que el movimiento fisiológico tiene un papel protagonista. Éstos son, por un lado, la estimación robusta de parámetros de rotación y esfuerzo miocárdico a partir de imágenes de MR-Tagging dinámica para el diagnóstico y clasificación de cardiomiopatías y, por otro, la reconstrucción de mapas del coeficiente de difusión aparente (ADC) a alta resolución y con alta relación señal a ruido (SNR) a partir de adquisiciones de imagen ponderada en difusión (DWI) multiparamétrica en el hígado.Departamento de Teoría de la Señal y Comunicaciones e Ingeniería TelemáticaDoctorado en Tecnologías de la Información y las Telecomunicacione

Quantifying inter-fraction cardiac substructure displacement during radiotherapy via magnetic resonance imaging guidance

Emerging evidence suggests cardiac substructures are highly radiosensitive during radiation therapy for cancer treatment. However, variability in substructure position after tumor localization has not been well characterized. This study quantifies inter-fraction displacement and planning organ at risk volumes (PRVs) of substructures by leveraging the excellent soft tissue contrast of magnetic resonance imaging (MRI). Eighteen retrospectively evaluated patients underwent radiotherapy for intrathoracic tumors with a 0.35 T MRI-guided linear accelerator. Imaging was acquired at a 17–25 s breath-hold (resolution 1.5 × 1.5 × 3 mm3). Three to four daily MRIs per patient (n = 71) were rigidly registered to the planning MRI-simulation based on tumor matching. Deep learning or atlas-based segmentation propagated 13 substructures (e.g., chambers, coronary arteries, great vessels) to daily MRIs and were verified by two radiation oncologists. Daily centroid displacements from MRI-simulation were quantified and PRVs were calculated. Across substructures, inter-fraction displacements for 14% in the left–right, 18% in the anterior-posterior, and 21% of fractions in the superior-inferior were \u3e 5 mm. Due to lack of breath-hold compliance, ~4% of all structures shifted \u3e 10 mm in any axis. For the chambers, median displacements were 1.8, 1.9, and 2.2 mm in the left–right, anterior-posterior, and superior-inferior axis, respectively. Great vessels demonstrated larger displacements (\u3e 3 mm) in the superior-inferior axis (43% of shifts) and were only 25% (left–right) and 29% (anterior-posterior) elsewhere. PRVs from 3 to 5 mm were determined as anisotropic substructure-specific margins. This exploratory work derived substructure-specific safety margins to ensure highly effective cardiac sparing. Findings require validation in a larger cohort for robust margin derivation and for applications in prospective clinical trials

MR imaging of left-ventricular function : novel image acquisition and analysis techniques.

Many cardiac diseases, such as myocardial ischemia, secondary to coronary artery disease, may be identified and localized through the analysis of cardiac deformations. Early efforts for quantifying ventricular wall motion used surgical implantation and tracking of radiopaque markers with X-ray imaging in canine hearts [1]. Such techniques are invasive and affect the regional motion pattern of the ventricular wall during the marker tracking process and, clearly are not feasible clinically. Noninvasive imaging techniques are vital and have been widely applied to the clinic. MRI is a noninvasive imaging technique with the capability to monitor and assess the progression of cardiovascular diseases (CVD) so that effective procedures for the care and treatment of patients can be developed by physicians and researchers. It is capable of providing 3D analysis of global and regional cardiac function with great accuracy and reproducibility. In the past few years, numerous efforts have been devoted to cardiac motion recovery and deformation analysis from MR imaging sequences. In order to assess cardiac function, there are two categories of indices that are used: global and regional indices. Global indices include ejection fraction, cavity volume, and myocardial mass [2]. They are important indices for cardiac disease diagnosis. However, these global indices are not specific for regional analysis. A quantitative assessment of regional parameters may prove beneficial for the diagnosis of disease and evaluation of severity and the quantification of treatment [3]. Local measures, such as wall deformation and strain in all regions of the heart, can provide objective regional quantification of ventricular wall function and relate to the location and extent of ischemic injury. This dissertation is concerned with the development of novel MR imaging techniques and image postprocessing algorithms to analyze left ventricular deformations. A novel pulse sequence, termed Orthogonal CSPAMM (OCSPAMM), has been proposed which results in the same acquisition time as SPAMM for 2D deformation estimation while keeping the main advantages of CSPAMM [4,5]: i.e., maintaining tag contrast through-out the ECG cycle. Different from CSPAMM, in OCSPAMM the second tagging pulse orientation is rotated 90 degrees relative to the first one so that motion information can be obtained simultaneously in two directions. This reduces the acquisition time by a factor of two as compared to the traditional CSPAMM, in which two separate imaging sequences are applied per acquisition. With the application of OCSPAMM, the effect of tag fading encountered in SPAMM tagging due to Tl relaxation is mitigated and tag deformations can be visualized for the entire cardiac cycle, including diastolic phases. A multilevel B-spline fitting method (MBS) has been proposed which incorporates phase-based displacement information for accurate calculation of 2D motion and strain from tagged MRI [6, 7]. The proposed method combines the advantages of continuity and smoothness of MBS, and makes use of phase information derived from tagged MR images. Compared to previous 2D B-spline-based deformation analysis methods, MBS has the following advantages: 1) It can simultaneously achieve a smooth deformation while accurately approximating the given data set; 2) Computationally, it is very fast; and 3) It can produce more accurate deformation results. Since the tag intersections (intersections between two tag lines) can be extracted accurately and are more or less distributed evenly over the myocardium, MBS has proven effective for 2D cardiac motion tracking. To derive phase-based displacements, 2D HARP and SinMod analysis techniques [8,9] were employed. By producing virtual tags from HARP /SinMod and calculating intersections of virtual tag lines, more data points are obtained. In the reference frame, virtual tag lines are the isoparametric curves of an undeformed 2D B-spline model. In subsequent frames, the locations of intersections of virtual tag lines over the myocardium are updated with phase-based displacement. The advantage of the technique is that in acquiring denser myocardial displacements, it uses both real and virtual tag line intersections. It is fast and more accurate than 2D HARP and SinMod tracking. A novel 3D sine wave modeling (3D SinMod) approach for automatic analysis of 3D cardiac deformations has been proposed [10]. An accelerated 3D complementary spatial modulation of magnetization (CSPAMM) tagging technique [11] was used to acquire complete 3D+t tagged MR data sets of the whole heart (3 dynamic CSPAMM tagged MRI volume with tags in different orientations), in-vivo, in 54 heart beats and within 3 breath-holds. In 3D SinMod, the intensity distribution around each pixel is modeled as a cosine wave front. The principle behind 3D SinMod tracking is that both phase and frequency for each voxel are determined directly from the frequency analysis and the displacement is calculated from the quotient of phase difference and local frequency. The deformation fields clearly demonstrate longitudinal shortening during systole. The contraction of the LV base towards the apex as well as the torsional motion between basal and apical slices is clearly observable from the displacements. 3D SinMod can automatically process the image data to derive measures of motion, deformations, and strains between consecutive pair of tagged volumes in 17 seconds. Therefore, comprehensive 4D imaging and postprocessing for determination of ventricular function is now possible in under 10 minutes. For validation of 3D SinMod, 7 3D+t CSPAMM data sets of healthy subjects have been processed. Comparison of mid-wall contour deformations and circumferential shortening results by 3D SinMod showed good agreement with those by 3D HARP. Tag lines tracked by the proposed technique were also compared with manually delineated ones. The average errors calculated for the systolic phase of the cardiac cycles were in the sub-pixel range

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

Brain and Head-and-Neck MRI in Immobilization Mask: A Practical Solution for MR-Only Radiotherapy

In brain/head-and-neck radiotherapy (RT), thermoplastic immobilization masks guarantee reproducible patient positioning in treatment position between MRI, CT, and irradiation. Since immobilization masks do not fit in the diagnostic MR head/head-and-neck coils, flexible surface coils are used for MRI imaging in clinical practice. These coils are placed around the head/neck, in contact with the immobilization masks. However, the positioning of these flexible coils is technician dependent, thus leading to poor image reproducibility. Additionally, flexible surface coils have an inferior signal-to-noise-ratio (SNR) compared to diagnostic coils. The aim of this work was to create a new immobilization setup which fits into the diagnostic MR coils in order to enhance MR image quality and reproducibility. For this purpose, a practical immobilization setup was constructed. The performances of the standard clinical and the proposed setups were compared with four tests: SNR, image quality, motion restriction, and reproducibility of inter-fraction subject positioning. The new immobilization setup resulted in 3.4 times higher SNR values on average than the standard setup, except directly below the flexible surface coils where similar SNR was observed. Overall, the image quality was superior for brain/head-and-neck images acquired with the proposed RT setup. Comparable motion restriction in feet-head/left-right directions (maximum motion ≈1 mm) and comparable inter-fraction repositioning accuracy (mean inter-fraction movement 1 ± 0.5 mm) were observed for the standard and the new setup

Deformable Groupwise Registration Using a Locally Low-Rank Dissimilarity Metric for Myocardial Strain Estimation from Cardiac Cine MRI Images

Objective: Cardiovascular magnetic resonance-feature tracking (CMR-FT) represents a group of methods for myocardial strain estimation from cardiac cine MRI images. Established CMR-FT methods are mainly based on optical flow or pairwise registration. However, these methods suffer from either inaccurate estimation of large motion or drift effect caused by accumulative tracking errors. In this work, we propose a deformable groupwise registration method using a locally low-rank (LLR) dissimilarity metric for CMR-FT. Methods: The proposed method (Groupwise-LLR) tracks the feature points by a groupwise registration-based two-step strategy. Unlike the globally low-rank (GLR) dissimilarity metric, the proposed LLR metric imposes low-rankness on local image patches rather than the whole image. We quantitatively compared Groupwise-LLR with the Farneback optical flow, a pairwise registration method, and a GLR-based groupwise registration method on simulated and in vivo datasets. Results: Results from the simulated dataset showed that Groupwise-LLR achieved more accurate tracking and strain estimation compared with the other methods. Results from the in vivo dataset showed that Groupwise-LLR achieved more accurate tracking and elimination of the drift effect in late-diastole. Inter-observer reproducibility of strain estimates was similar between all studied methods. Conclusion: The proposed method estimates myocardial strains more accurately due to the application of a groupwise registration-based tracking strategy and an LLR-based dissimilarity metric. Significance: The proposed CMR-FT method may facilitate more accurate estimation of myocardial strains, especially in diastole, for clinical assessments of cardiac dysfunction