Meta-Learning Initializations for Interactive Medical Image Registration

We present a meta-learning framework for interactive medical image registration. Our proposed framework comprises three components: a learning-based medical image registration algorithm, a form of user interaction that refines registration at inference, and a meta-learning protocol that learns a rapidly adaptable network initialization. This paper describes a specific algorithm that implements the registration, interaction and meta-learning protocol for our exemplar clinical application: registration of magnetic resonance (MR) imaging to interactively acquired, sparsely-sampled transrectal ultrasound (TRUS) images. Our approach obtains comparable registration error (4.26 mm) to the best-performing non-interactive learning-based 3D-to-3D method (3.97 mm) while requiring only a fraction of the data, and occurring in real-time during acquisition. Applying sparsely sampled data to non-interactive methods yields higher registration errors (6.26 mm), demonstrating the effectiveness of interactive MR-TRUS registration, which may be applied intraoperatively given the real-time nature of the adaptation process.Comment: 11 pages, 10 figures. Paper accepted to IEEE Transactions on Medical Imaging (October 26 2022

Biomechanical Modeling and Inverse Problem Based Elasticity Imaging for Prostate Cancer Diagnosis

Early detection of prostate cancer plays an important role in successful prostate cancer treatment. This requires screening the prostate periodically after the age of 50. If screening tests lead to prostate cancer suspicion, prostate needle biopsy is administered which is still considered as the clinical gold standard for prostate cancer diagnosis. Given that needle biopsy is invasive and is associated with issues including discomfort and infection, it is desirable to develop a prostate cancer diagnosis system that has high sensitivity and specificity for early detection with a potential to improve needle biopsy outcome. Given the complexity and variability of prostate cancer pathologies, many research groups have been pursuing multi-parametric imaging approach as no single modality imaging technique has proven to be adequate. While imaging additional tissue properties increases the chance of reliable prostate cancer detection and diagnosis, selecting an additional property needs to be done carefully by considering clinical acceptability and cost. Clinical acceptability entails ease with respect to both operating by the radiologist and patient comfort. In this work, effective tissue biomechanics based diagnostic techniques are proposed for prostate cancer assessment with the aim of early detection and minimizing the numbers of prostate biopsies. The techniques take advantage of the low cost, widely available and well established TRUS imaging method. The proposed techniques include novel elastography methods which were formulated based on an inverse finite element frame work. Conventional finite element analysis is known to have high computational complexity, hence computation time demanding. This renders the proposed elastography methods not suitable for real-time applications. To address this issue, an accelerated finite element method was proposed which proved to be suitable for prostate elasticity reconstruction. In this method, accurate finite element analysis of a large number of prostates undergoing TRUS probe loadings was performed. Geometry input and displacement and stress fields output obtained from the analysis were used to train a neural network mapping function to be used for elastopgraphy imaging of prostate cancer patients. The last part of the research presented in this thesis tackles an issue with the current 3D TRUS prostate needle biopsy. Current 3D TRUS prostate needle biopsy systems require registering preoperative 3D TRUS to intra-operative 2D TRUS images. Such image registration is time-consuming while its real-time implementation is yet to be developed. To bypass this registration step, concept of a robotic system was proposed which can reliably determine the preoperative TRUS probe position relative to the prostate to place at the same position relative to the prostate intra-operatively. For this purpose, a contact pressure feedback system is proposed to ensure similar prostate deformation during 3D and 2D image acquisition in order to bypass the registration step

Medical Image Registration Using Deep Neural Networks

Registration is a fundamental problem in medical image analysis wherein images are transformed spatially to align corresponding anatomical structures in each image. Recently, the development of learning-based methods, which exploit deep neural networks and can outperform classical iterative methods, has received considerable interest from the research community. This interest is due in part to the substantially reduced computational requirements that learning-based methods have during inference, which makes them particularly well-suited to real-time registration applications. Despite these successes, learning-based methods can perform poorly when applied to images from different modalities where intensity characteristics can vary greatly, such as in magnetic resonance and ultrasound imaging. Moreover, registration performance is often demonstrated on well-curated datasets, closely matching the distribution of the training data. This makes it difficult to determine whether demonstrated performance accurately represents the generalization and robustness required for clinical use. This thesis presents learning-based methods which address the aforementioned difficulties by utilizing intuitive point-set-based representations, user interaction and meta-learning-based training strategies. Primarily, this is demonstrated with a focus on the non-rigid registration of 3D magnetic resonance imaging to sparse 2D transrectal ultrasound images to assist in the delivery of targeted prostate biopsies. While conventional systematic prostate biopsy methods can require many samples to be taken to confidently produce a diagnosis, tumor-targeted approaches have shown improved patient, diagnostic, and disease management outcomes with fewer samples. However, the available intraoperative transrectal ultrasound imaging alone is insufficient for accurate targeted guidance. As such, this exemplar application is used to illustrate the effectiveness of sparse, interactively-acquired ultrasound imaging for real-time, interventional registration. The presented methods are found to improve registration accuracy, relative to state-of-the-art, with substantially lower computation time and require a fraction of the data at inference. As a result, these methods are particularly attractive given their potential for real-time registration in interventional applications

Biomechanical modelling of probe to tissue interaction during ultrasound scanning

Purpose: Biomechanical simulation of anatomical deformations caused by ultrasound probe pressure is of outstanding importance for several applications, from the testing of robotic acquisition systems to multi-modal image fusion and development of ultrasound training platforms. Different approaches can be exploited for modelling the probe-tissue interaction, each achieving different trade-offs among accuracy, computation time and stability. Methods: We assess the performances of different strategies based on the finite element method for modelling the interaction between the rigid probe and soft tissues. Probe\u2013tissue contact is modelled using (i) penalty forces, (ii) constraint forces, and (iii) by prescribing the displacement of the mesh surface nodes. These methods are tested in the challenging context of ultrasound scanning of the breast, an organ undergoing large nonlinear deformations during the procedure. Results: The obtained results are evaluated against those of a non-physically based method. While all methods achieve similar accuracy, performance in terms of stability and speed shows high variability, especially for those methods modelling the contacts explicitly. Overall, prescribing surface displacements is the approach with best performances, but it requires prior knowledge of the contact area and probe trajectory. Conclusions: In this work, we present different strategies for modelling probe\u2013tissue interaction, each able to achieve different compromises among accuracy, speed and stability. The choice of the preferred approach highly depends on the requirements of the specific clinical application. Since the presented methodologies can be applied to describe general tool\u2013tissue interactions, this work can be seen as a reference for researchers seeking the most appropriate strategy to model anatomical deformation induced by the interaction with medical tools

Realistic tool-tissue interaction models for surgical simulation and planning

Surgical simulators present a safe and potentially effective method for surgical training, and can also be used in pre- and intra-operative surgical planning. Realistic modeling of medical interventions involving tool-tissue interactions has been considered to be a key requirement in the development of high-fidelity simulators and planners. The soft-tissue constitutive laws, organ geometry and boundary conditions imposed by the connective tissues surrounding the organ, and the shape of the surgical tool interacting with the organ are some of the factors that govern the accuracy of medical intervention planning.\ud \ud This thesis is divided into three parts. First, we compare the accuracy of linear and nonlinear constitutive laws for tissue. An important consequence of nonlinear models is the Poynting effect, in which shearing of tissue results in normal force; this effect is not seen in a linear elastic model. The magnitude of the normal force for myocardial tissue is shown to be larger than the human contact force discrimination threshold. Further, in order to investigate and quantify the role of the Poynting effect on material discrimination, we perform a multidimensional scaling study. Second, we consider the effects of organ geometry and boundary constraints in needle path planning. Using medical images and tissue mechanical properties, we develop a model of the prostate and surrounding organs. We show that, for needle procedures such as biopsy or brachytherapy, organ geometry and boundary constraints have more impact on target motion than tissue material parameters. Finally, we investigate the effects surgical tool shape on the accuracy of medical intervention planning. We consider the specific case of robotic needle steering, in which asymmetry of a bevel-tip needle results in the needle naturally bending when it is inserted into soft tissue. We present an analytical and finite element (FE) model for the loads developed at the bevel tip during needle-tissue interaction. The analytical model explains trends observed in the experiments. We incorporated physical parameters (rupture toughness and nonlinear material elasticity) into the FE model that included both contact and cohesive zone models to simulate tissue cleavage. The model shows that the tip forces are sensitive to the rupture toughness. In order to model the mechanics of deflection of the needle, we use an energy-based formulation that incorporates tissue-specific parameters such as rupture toughness, nonlinear material elasticity, and interaction stiffness, and needle geometric and material properties. Simulation results follow similar trends (deflection and radius of curvature) to those observed in macroscopic experimental studies of a robot-driven needle interacting with gels

Position-based modeling of lesion displacement in Ultrasound-guided breast biopsy

International audiencePurpose Although ultrasound (US) images represent the most popular modality for guiding breast biopsy, malignant regions are often missed by sonography, thus preventing accurate lesion localization which is essential for a successful procedure. Biomechanical models can support the localization of suspicious areas identified on a pre-operative image during US scanning since they are able to account for anatomical deformations resulting from US probe pressure. We propose a deformation model which relies on position-based dynamics (PBD) approach to predict the displacement of internal targets induced by probe interaction during US acquisition. Methods The PBD implementation available in NVIDIA FleX is exploited to create an anatomical model capable of deforming online. Simulation parameters are initialized on a calibration phantom under different levels of probe-induced deformations, then they are fine-tuned by minimizing the localization error of a US-visible landmark of a realistic breast phantom. The updated model is used to estimate the displacement of other internal lesions due to probe-tissue interaction. Results The localization error obtained when applying the PBD model remains below 11 mm for all the tumors even for input displacements in the order of 30 mm. This proposed method obtains results aligned with FE models with faster computational performance, suitable for real-time applications. In addition, it outperforms rigid model used to track lesion position in US-guided breast biopsies, at least halving the localization error for all the displacement ranges considered. 2 Eleonora Tagliabue et al. Conclusions Position-based dynamics approach has proved to be successful in modeling breast tissue deformations during US acquisition. Its stability, accuracy and real-time performance make such model suitable for tracking lesions displacement during US-guided breast biopsy

3D fusion of histology to multi-parametric MRI for prostate cancer imaging evaluation and lesion-targeted treatment planning

Multi-parametric magnetic resonance imaging (mpMRI) of localized prostate cancer has the potential to support detection, staging and localization of tumors, as well as selection, delivery and monitoring of treatments. Delineating prostate cancer tumors on imaging could potentially further support the clinical workflow by enabling precise monitoring of tumor burden in active-surveillance patients, optimized targeting of image-guided biopsies, and targeted delivery of treatments to decrease morbidity and improve outcomes. Evaluating the performance of mpMRI for prostate cancer imaging and delineation ideally includes comparison to an accurately registered reference standard, such as prostatectomy histology, for the locations of tumor boundaries on mpMRI. There are key gaps in knowledge regarding how to accurately register histological reference standards to imaging, and consequently further gaps in knowledge regarding the suitability of mpMRI for tasks, such as tumor delineation, that require such reference standards for evaluation. To obtain an understanding of the magnitude of the mpMRI-histology registration problem, we quantified the position, orientation and deformation of whole-mount histology sections relative to the formalin-fixed tissue slices from which they were cut. We found that (1) modeling isotropic scaling accounted for the majority of the deformation with a further small but statistically significant improvement from modeling affine transformation, and (2) due to the depth (mean±standard deviation (SD) 1.1±0.4 mm) and orientation (mean±SD 1.5±0.9°) of the sectioning, the assumption that histology sections are cut from the front faces of tissue slices, common in previous approaches, introduced a mean error of 0.7 mm. To determine the potential consequences of seemingly small registration errors such as described above, we investigated the impact of registration accuracy on the statistical power of imaging validation studies using a co-registered spatial reference standard (e.g. histology images) by deriving novel statistical power formulae that incorporate registration error. We illustrated, through a case study modeled on a prostate cancer imaging trial at our centre, that submillimeter differences in registration error can have a substantial impact on the required sample sizes (and therefore also the study cost) for studies aiming to detect mpMRI signal differences due to 0.5 – 2.0 cm3 prostate tumors. With the aim of achieving highly accurate mpMRI-histology registrations without disrupting the clinical pathology workflow, we developed a three-stage method for accurately registering 2D whole-mount histology images to pre-prostatectomy mpMRI that allowed flexible placement of cuts during slicing for pathology and avoided the assumption that histology sections are cut from the front faces of tissue slices. The method comprised a 3D reconstruction of histology images, followed by 3D–3D ex vivo–in vivo and in vivo–in vivo image transformations. The 3D reconstruction method minimized fiducial registration error between cross-sections of non-disruptive histology- and ex-vivo-MRI-visible strand-shaped fiducials to reconstruct histology images into the coordinate system of an ex vivo MR image. We quantified the mean±standard deviation target registration error of the reconstruction to be 0.7±0.4 mm, based on the post-reconstruction misalignment of intrinsic landmark pairs. We also compared our fiducial-based reconstruction to an alternative reconstruction based on mutual-information-based registration, an established method for multi-modality registration. We found that the mean target registration error for the fiducial-based method (0.7 mm) was lower than that for the mutual-information-based method (1.2 mm), and that the mutual-information-based method was less robust to initialization error due to multiple sources of error, including the optimizer and the mutual information similarity metric. The second stage of the histology–mpMRI registration used interactively defined 3D–3D deformable thin-plate-spline transformations to align ex vivo to in vivo MR images to compensate for deformation due to endorectal MR coil positioning, surgical resection and formalin fixation. The third stage used interactively defined 3D–3D rigid or thin-plate-spline transformations to co-register in vivo mpMRI images to compensate for patient motion and image distortion. The combined mean registration error of the histology–mpMRI registration was quantified to be 2 mm using manually identified intrinsic landmark pairs. Our data set, comprising mpMRI, target volumes contoured by four observers and co-registered contoured and graded histology images, was used to quantify the positive predictive values and variability of observer scoring of lesions following the Prostate Imaging Reporting and Data System (PI-RADS) guidelines, the variability of target volume contouring, and appropriate expansion margins from target volumes to achieve coverage of histologically defined cancer. The analysis of lesion scoring showed that a PI-RADS overall cancer likelihood of 5, denoting “highly likely cancer”, had a positive predictive value of 85% for Gleason 7 cancer (and 93% for lesions with volumes \u3e0.5 cm3 measured on mpMRI) and that PI-RADS scores were positively correlated with histological grade (ρ=0.6). However, the analysis also showed interobserver differences in PI-RADS score of 0.6 to 1.2 (on a 5-point scale) and an agreement kappa value of only 0.30. The analysis of target volume contouring showed that target volume contours with suitable margins can achieve near-complete histological coverage for detected lesions, despite the presence of high interobserver spatial variability in target volumes. Prostate cancer imaging and delineation have the potential to support multiple stages in the management of localized prostate cancer. Targeted biopsy procedures with optimized targeting based on tumor delineation may help distinguish patients who need treatment from those who need active surveillance. Ongoing monitoring of tumor burden based on delineation in patients undergoing active surveillance may help identify those who need to progress to therapy early while the cancer is still curable. Preferentially targeting therapies at delineated target volumes may lower the morbidity associated with aggressive cancer treatment and improve outcomes in low-intermediate-risk patients. Measurements of the accuracy and variability of lesion scoring and target volume contouring on mpMRI will clarify its value in supporting these roles

SMART IMAGE-GUIDED NEEDLE INSERTION FOR TISSUE BIOPSY

M.S

NON-RIGID BODY MECHANICAL PROPERTY RECOVERY FROM IMAGES AND VIDEOS

Material property has great importance in surgical simulation and virtual reality. The mechanical properties of the human soft tissue are critical to characterize the tissue deformation of each patient. Studies have shown that the tissue stiffness described by the tissue properties may indicate abnormal pathological process. The (recovered) elasticity parameters can assist surgeons to perform better pre-op surgical planning and enable medical robots to carry out personalized surgical procedures. Traditional elasticity parameters estimation methods rely largely on known external forces measured by special devices and strain field estimated by landmarks on the deformable bodies. Or they are limited to mechanical property estimation for quasi-static deformation. For virtual reality applications such as virtual try-on, garment material capturing is of equal significance as the geometry reconstruction. In this thesis, I present novel approaches for automatically estimating the material properties of soft bodies from images or from a video capturing the motion of the deformable body. I use a coupled simulation-optimization-identification framework to deform one soft body at its original, non-deformed state to match the deformed geometry of the same object in its deformed state. The optimal set of material parameters is thereby determined by minimizing the error metric function. This method can simultaneously recover the elasticity parameters of multiple regions of soft bodies using Finite Element Method-based simulation (of either linear or nonlinear materials undergoing large deformation) and particle-swarm optimization methods. I demonstrate the effectiveness of this approach on real-time interaction with virtual organs in patient-specific surgical simulation, using parameters acquired from low-resolution medical images. With the recovered elasticity parameters and the age of the prostate cancer patients as features, I build a cancer grading and staging classifier. The classifier achieves up to 91% for predicting cancer T-Stage and 88% for predicting Gleason score. To recover the mechanical properties of soft bodies from a video, I propose a method which couples statistical graphical model with FEM simulation. Using this method, I can recover the material properties of a soft ball from a high-speed camera video that captures the motion of the ball. Furthermore, I extend the material recovery framework to fabric material identification. I propose a novel method for garment material extraction from a single-view image and a learning based cloth material recovery method from a video recording the motion of the cloth. Most recent garment capturing techniques rely on acquiring multiple views of clothing, which may not always be readily available, especially in the case of pre-existing photographs from the web. As an alternative, I propose a method that can compute a 3D model of a human body and its outfit from a single photograph with little human interaction. My proposed learning-based cloth material type recovery method exploits simulated data-set and deep neural network. I demonstrate the effectiveness of my algorithms by re-purposing the reconstructed garments for virtual try-on, garment transfer, and cloth animation on digital characters. With the recovered mechanical properties, one can construct a virtual world with soft objects exhibiting real-world behaviors.Doctor of Philosoph

Patient-specific simulation environment for surgical planning and preoperative rehearsal

Surgical simulation is common practice in the fields of surgical education and training. Numerous surgical simulators are available from commercial and academic organisations for the generic modelling of surgical tasks. However, a simulation platform is still yet to be found that fulfils the key requirements expected for patient-specific surgical simulation of soft tissue, with an effective translation into clinical practice. Patient-specific modelling is possible, but to date has been time-consuming, and consequently costly, because data preparation can be technically demanding. This motivated the research developed herein, which addresses the main challenges of biomechanical modelling for patient-specific surgical simulation. A novel implementation of soft tissue deformation and estimation of the patient-specific intraoperative environment is achieved using a position-based dynamics approach. This modelling approach overcomes the limitations derived from traditional physically-based approaches, by providing a simulation for patient-specific models with visual and physical accuracy, stability and real-time interaction. As a geometrically- based method, a calibration of the simulation parameters is performed and the simulation framework is successfully validated through experimental studies. The capabilities of the simulation platform are demonstrated by the integration of different surgical planning applications that are found relevant in the context of kidney cancer surgery. The simulation of pneumoperitoneum facilitates trocar placement planning and intraoperative surgical navigation. The implementation of deformable ultrasound simulation can assist surgeons in improving their scanning technique and definition of an optimal procedural strategy. Furthermore, the simulation framework has the potential to support the development and assessment of hypotheses that cannot be tested in vivo. Specifically, the evaluation of feedback modalities, as a response to user-model interaction, demonstrates improved performance and justifies the need to integrate a feedback framework in the robot-assisted surgical setting.Open Acces