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

Enhancing Registration for Image-Guided Neurosurgery

Pharmacologically refractive temporal lobe epilepsy and malignant glioma brain tumours are examples of pathologies that are clinically managed through neurosurgical intervention. The aims of neurosurgery are, where possible, to perform a resection of the surgical target while minimising morbidity to critical structures in the vicinity of the resected brain area. Image-guidance technology aims to assist this task by displaying a model of brain anatomy to the surgical team, which may include an overlay of surgical planning information derived from preoperative scanning such as the segmented resection target and nearby critical brain structures. Accurate neuronavigation is hindered by brain shift, the complex and non-rigid deformation of the brain that arises during surgery, which invalidates assumed rigid geometric correspondence between the neuronavigation model and the true shifted positions of relevant brain areas. Imaging using an interventional MRI (iMRI) scanner in a next-generation operating room can serve as a reference for intraoperative updates of the neuronavigation. An established clinical image processing workflow for iMRI-based guidance involves the correction of relevant imaging artefacts and the estimation of deformation due to brain shift based on non-rigid registration. The present thesis introduces two refinements aimed at enhancing the accuracy and reliability of iMRI-based guidance. A method is presented for the correction of magnetic susceptibility artefacts, which affect diffusion and functional MRI datasets, based on simulating magnetic field variation in the head from structural iMRI scans. Next, a method is presented for estimating brain shift using discrete non-rigid registration and a novel local similarity measure equipped with an edge-preserving property which is shown to improve the accuracy of the estimated deformation in the vicinity of the resected area for a number of cases of surgery performed for the management of temporal lobe epilepsy and glioma

Optic Nerve Deformation by Eye Movements

Ocular rotation can cause mechanical deformation of the optic nerve head and surrounding tissues. During extreme angles of gaze, the optic nerve can become stretched and impose strain on other ocular tissues. Over a lifetime, the ill effects of repetitive mechanical injury from large adduction can compound, resulting in progressive optic neuropathy in some glaucoma patients.We investigated the etiology of this form of glaucoma through a series of papers focusing on anatomical analysis of the human optic nerve from donated tissue and clinical studies utilizing optical coherence tomography (OCT) and confocal scanning laser ophthalmoscopy (cSLO). The optic nerve is surrounded and protected by a bi-layered dural sheath that bears the bulk of exerted mechanical force. Elastin fibers embedded within the sheath and peripapillary tissues around the nerve head form a three-dimensional meshwork that reinforces the tissue against mechanical strain. While the tissue at the globe optic nerve junction is heavily fortified with organized layers of collagen and elastin fibers, irregularities in the elastin fiber arrangement resulting in large dense elastin deposits were observed to correlate with older age. These elastin deposits could be a pathologic byproduct of optic nerve injury from mechanical strain, or serve as a protective mechanism to further reinforce the ocular tissues.In OCT studies, adduction of angles beyond 26� caused marked deformation of the peripapillary tissues around the optic nerve head, and choroidal volume change. cSLO imaging showed similar deformations of the retina surface during large angle adduction. Ocular tissue of younger subjects appears more compliant, while those of glaucoma patients were stiffer and thus experienced less deformation.We explored possible therapies for optic nerve traction during eye movement. Using collagen crosslinking to fortify ocular tissue, we observed that exposure to riboflavin and UV light can stiffen scleral tissue. In addition, we investigated whether prostaglandin agonists could be used to reduce ocular fat and found that topical administration of these agonists had insignificant effects on the retrobulbar fat

Dosimetry of Photon and Proton MRI Guided Radiotherapy Beams using Silicon Array Dosimeters

The integration of online magnetic resonance imaging (MRI) with photon and pro-ton radiotherapy has potential to overcome the soft tissue contrast limitations of the current standard of care kV-image guided radiotherapy in some challenging treat-ment sites. By directly visualising soft tissue targets and organs at risk, removing the dependence on surrogates for image guidance, it is expected there will be a decrease in the geometric uncertainties related to daily patient setup. This new approach to image guided radiotherapy presents unique challenges due to the permanent mag-netic field of the integrated MRI unit. The trajectory of charged particles including dose depositing secondary electrons are perturbed by the magnetic field, adding to the challenge of calculating the patient dosimetry and validating the calculation with measurement as is standard practice in radiotherapy. The magnetic field may also effect the operation and response of radiation detectors and a method of accurately characterising the influence of the magnetic field on detector response and operation is required. This thesis reports progress made towards real time high spatial resolution dosime-try of photon and proton MRI guided radiotherapy beams using novel monolithic silicon detectors designed at the Centre for Medical Radiation Physics (CMRP). One challenge in experimentally characterising the magnetic field effects on a radiation detectors operation is how to perform dosimetry measurements with and without a magnetic field of varying strength and orientation from a single radiation source as this is not feasible on existing MRI linacs with a permanent magnetic field of fixed strength. A bespoke semi-portable magnet device was developed to meet this need. The device employs an adjustable iron yoke and focusing cones to vary the magnetic field of the central volume, a 0.3 T field can be achieved for volume to 10 x 10 x 10 cm3 and up to a 1.2 T for a volume of at least 3 x 3 x 3 cm3. The device is de-signed to be used with a clinical linear accelerator in both inline and perpendicular magnetic field orientations to meet the challenge of detector characterisation. The performance of the magnetic field generated by the device was within ±2 % of finite element modelling predictions of all configurations tested

Finite Element Modeling Driven by Health Care and Aerospace Applications

This thesis concerns the development, analysis, and computer implementation of mesh generation algorithms encountered in finite element modeling in health care and aerospace. The finite element method can reduce a continuous system to a discrete idealization that can be solved in the same manner as a discrete system, provided the continuum is discretized into a finite number of simple geometric shapes (e.g., triangles in two dimensions or tetrahedrons in three dimensions). In health care, namely anatomic modeling, a discretization of the biological object is essential to compute tissue deformation for physics-based simulations. This thesis proposes an efficient procedure to convert 3-dimensional imaging data into adaptive lattice-based discretizations of well-shaped tetrahedra or mixed elements (i.e., tetrahedra, pentahedra and hexahedra). This method operates directly on segmented images, thus skipping a surface reconstruction that is required by traditional Computer-Aided Design (CAD)-based meshing techniques and is convoluted, especially in complex anatomic geometries. Our approach utilizes proper mesh gradation and tissue-specific multi-resolution, without sacrificing the fidelity and while maintaining a smooth surface to reflect a certain degree of visual reality. Image-to-mesh conversion can facilitate accurate computational modeling for biomechanical registration of Magnetic Resonance Imaging (MRI) in image-guided neurosurgery. Neuronavigation with deformable registration of preoperative MRI to intraoperative MRI allows the surgeon to view the location of surgical tools relative to the preoperative anatomical (MRI) or functional data (DT-MRI, fMRI), thereby avoiding damage to eloquent areas during tumor resection. This thesis presents a deformable registration framework that utilizes multi-tissue mesh adaptation to map preoperative MRI to intraoperative MRI of patients who have undergone a brain tumor resection. Our enhancements with mesh adaptation improve the accuracy of the registration by more than 5 times compared to rigid and traditional physics-based non-rigid registration, and by more than 4 times compared to publicly available B-Spline interpolation methods. The adaptive framework is parallelized for shared memory multiprocessor architectures. Performance analysis shows that this method could be applied, on average, in less than two minutes, achieving desirable speed for use in a clinical setting. The last part of this thesis focuses on finite element modeling of CAD data. This is an integral part of the design and optimization of components and assemblies in industry. We propose a new parallel mesh generator for efficient tetrahedralization of piecewise linear complex domains in aerospace. CAD-based meshing algorithms typically improve the shape of the elements in a post-processing step due to high complexity and cost of the operations involved. On the contrary, our method optimizes the shape of the elements throughout the generation process to obtain a maximum quality and utilizes high performance computing to reduce the overheads and improve end-user productivity. The proposed mesh generation technique is a combination of Advancing Front type point placement, direct point insertion, and parallel multi-threaded connectivity optimization schemes. The mesh optimization is based on a speculative (optimistic) approach that has been proven to perform well on hardware-shared memory. The experimental evaluation indicates that the high quality and performance attributes of this method see substantial improvement over existing state-of-the-art unstructured grid technology currently incorporated in several commercial systems. The proposed mesh generator will be part of an Extreme-Scale Anisotropic Mesh Generation Environment to meet industries expectations and NASA\u27s CFD visio

Innovative techniques to devise 3D-printed anatomical brain phantoms for morpho-functional medical imaging

Introduction. The Ph.D. thesis addresses the development of innovative techniques to create 3D-printed anatomical brain phantoms, which can be used for quantitative technical assessments on morpho-functional imaging devices, providing simulation accuracy not obtainable with currently available phantoms. 3D printing (3DP) technology is paving the way for advanced anatomical modelling in biomedical applications. Despite the potential already expressed by 3DP in this field, it is still little used for the realization of anthropomorphic phantoms of human organs with complex internal structures. Making an anthropomorphic phantom is very different from making a simple anatomical model and 3DP is still far from being plug-and-print. Hence, the need to develop ad-hoc techniques providing innovative solutions for the realization of anatomical phantoms with unique characteristics, and greater ease-of-use. Aim. The thesis explores the entire workflow (brain MRI images segmentation, 3D modelling and materialization) developed to prototype a new complex anthropomorphic brain phantom, which can simulate three brain compartments simultaneously: grey matter (GM), white matter (WM) and striatum (caudate nucleus and putamen, known to show a high uptake in nuclear medicine studies). The three separate chambers of the phantom will be filled with tissue-appropriate solutions characterized by different concentrations of radioisotope for PET/SPECT, para-/ferro-magnetic metals for MRI, and iodine for CT imaging. Methods. First, to design a 3D model of the brain phantom, it is necessary to segment MRI images and to extract an error-less STL (Standard Tessellation Language) description. Then, it is possible to materialize the prototype and test its functionality. - Image segmentation. Segmentation is one of the most critical steps in modelling. To this end, after demonstrating the proof-of-concept, a multi-parametric segmentation approach based on brain relaxometry was proposed. It includes a pre-processing step to estimate relaxation parameter maps (R1 = longitudinal relaxation rate, R2 = transverse relaxation rate, PD = proton density) from the signal intensities provided by MRI sequences of routine clinical protocols (3D-GrE T1-weighted, FLAIR and fast-T2-weighted sequences with ≤ 3 mm slice thickness). In the past, maps of R1, R2, and PD were obtained from Conventional Spin Echo (CSE) sequences, which are no longer suitable for clinical practice due to long acquisition times. Rehabilitating the multi-parametric segmentation based on relaxometry, the estimation of pseudo-relaxation maps allowed developing an innovative method for the simultaneous automatic segmentation of most of the brain structures (GM, WM, cerebrospinal fluid, thalamus, caudate nucleus, putamen, pallidus, nigra, red nucleus and dentate). This method allows the segmentation of higher resolution brain images for future brain phantom enhancements. - STL extraction. After segmentation, the 3D model of phantom is described in STL format, which represents the shapes through the approximation in manifold mesh (i.e., collection of triangles, which is continuous, without holes and with a positive – not zero – volume). For this purpose, we developed an automatic procedure to extract a single voxelized surface, tracing the anatomical interface between the phantom's compartments directly on the segmented images. Two tubes were designed for each compartment (one for filling and the other to facilitate the escape of air). The procedure automatically checks the continuity of the surface, ensuring that the 3D model could be exported in STL format, without errors, using a common image-to-STL conversion software. Threaded junctions were added to the phantom (for the hermetic closure) using a mesh processing software. The phantom's 3D model resulted correct and ready for 3DP. Prototyping. Finally, the most suitable 3DP technology is identified for the materialization. We investigated the material extrusion technology, named Fused Deposition Modeling (FDM), and the material jetting technology, named PolyJet. FDM resulted the best candidate for our purposes. It allowed materializing the phantom's hollow compartments in a single print, without having to print them in several parts to be reassembled later. FDM soluble internal support structures were completely removable after the materialization, unlike PolyJet supports. A critical aspect, which required a considerable effort to optimize the printing parameters, was the submillimetre thickness of the phantom walls, necessary to avoid distorting the imaging simulation. However, 3D printer manufacturers recommend maintaining a uniform wall thickness of at least 1 mm. The optimization of printing path made it possible to obtain strong, but not completely waterproof walls, approximately 0.5 mm thick. A sophisticated technique, based on the use of a polyvinyl-acetate solution, was developed to waterproof the internal and external phantom walls (necessary requirement for filling). A filling system was also designed to minimize the residual air bubbles, which could result in unwanted hypo-intensity (dark) areas in phantom-based imaging simulation. Discussions and conclusions. The phantom prototype was scanned trough CT and PET/CT to evaluate the realism of the brain simulation. None of the state-of-the-art brain phantoms allow such anatomical rendering of three brain compartments. Some represent only GM and WM, others only the striatum. Moreover, they typically have a poor anatomical yield, showing a reduced depth of the sulci and a not very faithful reproduction of the cerebral convolutions. The ability to simulate the three brain compartments simultaneously with greater accuracy, as well as the possibility of carrying out multimodality studies (PET/CT, PET/MRI), which represent the frontier of diagnostic imaging, give this device cutting-edge prospective characteristics. The effort to further customize 3DP technology for these applications is expected to increase significantly in the coming years