Label-driven weakly-supervised learning for multimodal deformable image registration

Spatially aligning medical images from different modalities remains a challenging task, especially for intraoperative applications that require fast and robust algorithms. We propose a weakly-supervised, label-driven formulation for learning 3D voxel correspondence from higher-level label correspondence, thereby bypassing classical intensity-based image similarity measures. During training, a convolutional neural network is optimised by outputting a dense displacement field (DDF) that warps a set of available anatomical labels from the moving image to match their corresponding counterparts in the fixed image. These label pairs, including solid organs, ducts, vessels, point landmarks and other ad hoc structures, are only required at training time and can be spatially aligned by minimising a cross-entropy function of the warped moving label and the fixed label. During inference, the trained network takes a new image pair to predict an optimal DDF, resulting in a fully-automatic, label-free, real-time and deformable registration. For interventional applications where large global transformation prevails, we also propose a neural network architecture to jointly optimise the global- and local displacements. Experiment results are presented based on cross-validating registrations of 111 pairs of T2-weighted magnetic resonance images and 3D transrectal ultrasound images from prostate cancer patients with a total of over 4000 anatomical labels, yielding a median target registration error of 4.2 mm on landmark centroids and a median Dice of 0.88 on prostate glands.Comment: Accepted to ISBI 201

Real-time multimodal image registration with partial intraoperative point-set data

We present Free Point Transformer (FPT) - a deep neural network architecture for non-rigid point-set registration. Consisting of two modules, a global feature extraction module and a point transformation module, FPT does not assume explicit constraints based on point vicinity, thereby overcoming a common requirement of previous learning-based point-set registration methods. FPT is designed to accept unordered and unstructured point-sets with a variable number of points and uses a "model-free" approach without heuristic constraints. Training FPT is flexible and involves minimizing an intuitive unsupervised loss function, but supervised, semi-supervised, and partially- or weakly-supervised training are also supported. This flexibility makes FPT amenable to multimodal image registration problems where the ground-truth deformations are difficult or impossible to measure. In this paper, we demonstrate the application of FPT to non-rigid registration of prostate magnetic resonance (MR) imaging and sparsely-sampled transrectal ultrasound (TRUS) images. The registration errors were 4.71 mm and 4.81 mm for complete TRUS imaging and sparsely-sampled TRUS imaging, respectively. The results indicate superior accuracy to the alternative rigid and non-rigid registration algorithms tested and substantially lower computation time. The rapid inference possible with FPT makes it particularly suitable for applications where real-time registration is beneficial

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

Deformable MRI to Transrectal Ultrasound Registration for Prostate Interventions Using Deep Learning

RÉSUMÉ: Le cancer de la prostate est l’un des principaux problèmes de santé publique dans le monde. Un diagnostic précoce du cancer de la prostate pourrait jouer un rôle vital dans le traitement des patients. Les procédures de biopsie sont utilisées à des fins de diagnostic. À cet égard, l’échographie transrectale (TRUS) est considérée comme un standard pour l’imagerie de la prostate lors d’une biopsie ou d’une curiethérapie. Cette technique d’imagerie est relativement peu coûteuse, peut scanner l’organe en temps réel et est sans radiation. Ainsi, les scans TRUS sont utilisés pour guider les cliniciens sur l’emplacement d’une tumeur à l’intérieur de la prostate. Le défi majeur réside dans le fait que les images TRUS ont une faible résolution et qualité d’image. Il est difficile de distinguer l’emplacement exact de la tumeur et l’étendue de la maladie. De plus, l’organe de la prostate subit d’importantes variations de forme au cours d’une intervention de la prostate, ce qui rend l’identification de la tumeur encore plus difficile.----------ABSTRACT: Prostate cancer is one of the major public health issues in the world. An accurate and early diagnosis of prostate cancer could play a vital role in the treatment of patients. Biopsy procedures are used for diagnosis purposes. In this regard, Transrectal Ultrasound (TRUS) is considered a standard for imaging the prostate during a biopsy or brachytherapy procedure. This imaging technique is comparatively low-cost, can scan the organ in real-time, and is radiation free. Thus, TRUS scans are used to guide the clinicians about the location of a tumor inside the prostate organ. The major challenge lies in the fact that TRUS images have low resolution and quality. This makes it difficult to distinguish the exact tumor location and the extent of the disease. In addition, the prostate organ undergoes important shape variations during a prostate intervention procedure, which makes the tumor identification even harder

Numerical Methods for Pulmonary Image Registration

Due to complexity and invisibility of human organs, diagnosticians need to analyze medical images to determine where the lesion region is, and which kind of disease is, in order to make precise diagnoses. For satisfying clinical purposes through analyzing medical images, registration plays an essential role. For instance, in Image-Guided Interventions (IGI) and computer-aided surgeries, patient anatomy is registered to preoperative images to guide surgeons complete procedures. Medical image registration is also very useful in surgical planning, monitoring disease progression and for atlas construction. Due to the significance, the theories, methods, and implementation method of image registration constitute fundamental knowledge in educational training for medical specialists. In this chapter, we focus on image registration of a specific human organ, i.e. the lung, which is prone to be lesioned. For pulmonary image registration, the improvement of the accuracy and how to obtain it in order to achieve clinical purposes represents an important problem which should seriously be addressed. In this chapter, we provide a survey which focuses on the role of image registration in educational training together with the state-of-the-art of pulmonary image registration. In the first part, we describe clinical applications of image registration introducing artificial organs in Simulation-based Education. In the second part, we summarize the common methods used in pulmonary image registration and analyze popular papers to obtain a survey of pulmonary image registration

Registration of magnetic resonance and ultrasound images for guiding prostate cancer interventions

Prostate cancer is a major international health problem with a large and rising incidence in many parts of the world. Transrectal ultrasound (TRUS) imaging is used routinely to guide surgical procedures, such as needle biopsy and a number of minimally-invasive therapies, but its limited ability to visualise prostate cancer is widely recognised. Magnetic resonance (MR) imaging techniques, on the other hand, have recently been developed that can provide clinically useful diagnostic information. Registration (or alignment) of MR and TRUS images during TRUS-guided surgical interventions potentially provides a cost-effective approach to augment TRUS images with clinically useful, MR-derived information (for example, tumour location, shape and size). This thesis describes a deformable image registration framework that enables automatic and/or semi-automatic alignment of MR and 3D TRUS images of the prostate gland. The method combines two technical developments in the field: First, a method for constructing patient-specific statistical shape models of prostate motion/deformation, based on learning from finite element simulations of gland motion using geometric data from a preoperative MR image, is proposed. Second, a novel “model-to-image” registration framework is developed to register this statistical shape model automatically to an intraoperative TRUS image. This registration approach is implemented using a novel model-to-image vector alignment (MIVA) algorithm, which maximises the likelihood of a particular instance of a statistical shape model given a voxel-intensity-based feature vector that represents an estimate of the surface normal vectors at the boundary of the organ in question. Using real patient data, the MR-TRUS registration accuracy of the new algorithm is validated using intra-prostatic anatomical landmarks. A rigorous and extensive validation analysis is also provided for assessing the image registration experiments. The final target registration error after performing 100 MR–TRUS registrations for each patient have a median of 2.40 mm, meaning that over 93% registrations may successfully hit the target representing a clinically significant lesion. The implemented registration algorithms took less than 30 seconds and 2 minutes for manually defined point- and normal vector features, respectively. The thesis concludes with a summary of potential applications and future research directions

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

Analysis of contrast-enhanced medical images.

Early detection of human organ diseases is of great importance for the accurate diagnosis and institution of appropriate therapies. This can potentially prevent progression to end-stage disease by detecting precursors that evaluate organ functionality. In addition, it also assists the clinicians for therapy evaluation, tracking diseases progression, and surgery operations. Advances in functional and contrast-enhanced (CE) medical images enabled accurate noninvasive evaluation of organ functionality due to their ability to provide superior anatomical and functional information about the tissue-of-interest. The main objective of this dissertation is to develop a computer-aided diagnostic (CAD) system for analyzing complex data from CE magnetic resonance imaging (MRI). The developed CAD system has been tested in three case studies: (i) early detection of acute renal transplant rejection, (ii) evaluation of myocardial perfusion in patients with ischemic heart disease after heart attack; and (iii), early detection of prostate cancer. However, developing a noninvasive CAD system for the analysis of CE medical images is subject to multiple challenges, including, but are not limited to, image noise and inhomogeneity, nonlinear signal intensity changes of the images over the time course of data acquisition, appearances and shape changes (deformations) of the organ-of-interest during data acquisition, determination of the best features (indexes) that describe the perfusion of a contrast agent (CA) into the tissue. To address these challenges, this dissertation focuses on building new mathematical models and learning techniques that facilitate accurate analysis of CAs perfusion in living organs and include: (i) accurate mathematical models for the segmentation of the object-of-interest, which integrate object shape and appearance features in terms of pixel/voxel-wise image intensities and their spatial interactions; (ii) motion correction techniques that combine both global and local models, which exploit geometric features, rather than image intensities to avoid problems associated with nonlinear intensity variations of the CE images; (iii) fusion of multiple features using the genetic algorithm. The proposed techniques have been integrated into CAD systems that have been tested in, but not limited to, three clinical studies. First, a noninvasive CAD system is proposed for the early and accurate diagnosis of acute renal transplant rejection using dynamic contrast-enhanced MRI (DCE-MRI). Acute rejection–the immunological response of the human immune system to a foreign kidney–is the most sever cause of renal dysfunction among other diagnostic possibilities, including acute tubular necrosis and immune drug toxicity. In the U.S., approximately 17,736 renal transplants are performed annually, and given the limited number of donors, transplanted kidney salvage is an important medical concern. Thus far, biopsy remains the gold standard for the assessment of renal transplant dysfunction, but only as the last resort because of its invasive nature, high cost, and potential morbidity rates. The diagnostic results of the proposed CAD system, based on the analysis of 50 independent in-vivo cases were 96% with a 95% confidence interval. These results clearly demonstrate the promise of the proposed image-based diagnostic CAD system as a supplement to the current technologies, such as nuclear imaging and ultrasonography, to determine the type of kidney dysfunction. Second, a comprehensive CAD system is developed for the characterization of myocardial perfusion and clinical status in heart failure and novel myoregeneration therapy using cardiac first-pass MRI (FP-MRI). Heart failure is considered the most important cause of morbidity and mortality in cardiovascular disease, which affects approximately 6 million U.S. patients annually. Ischemic heart disease is considered the most common underlying cause of heart failure. Therefore, the detection of the heart failure in its earliest forms is essential to prevent its relentless progression to premature death. While current medical studies focus on detecting pathological tissue and assessing contractile function of the diseased heart, this dissertation address the key issue of the effects of the myoregeneration therapy on the associated blood nutrient supply. Quantitative and qualitative assessment in a cohort of 24 perfusion data sets demonstrated the ability of the proposed framework to reveal regional perfusion improvements with therapy, and transmural perfusion differences across the myocardial wall; thus, it can aid in follow-up on treatment for patients undergoing the myoregeneration therapy. Finally, an image-based CAD system for early detection of prostate cancer using DCE-MRI is introduced. Prostate cancer is the most frequently diagnosed malignancy among men and remains the second leading cause of cancer-related death in the USA with more than 238,000 new cases and a mortality rate of about 30,000 in 2013. Therefore, early diagnosis of prostate cancer can improve the effectiveness of treatment and increase the patient’s chance of survival. Currently, needle biopsy is the gold standard for the diagnosis of prostate cancer. However, it is an invasive procedure with high costs and potential morbidity rates. Additionally, it has a higher possibility of producing false positive diagnosis due to relatively small needle biopsy samples. Application of the proposed CAD yield promising results in a cohort of 30 patients that would, in the near future, represent a supplement of the current technologies to determine prostate cancer type. The developed techniques have been compared to the state-of-the-art methods and demonstrated higher accuracy as shown in this dissertation. The proposed models (higher-order spatial interaction models, shape models, motion correction models, and perfusion analysis models) can be used in many of today’s CAD applications for early detection of a variety of diseases and medical conditions, and are expected to notably amplify the accuracy of CAD decisions based on the automated analysis of CE images

Segmentation of pelvic structures from preoperative images for surgical planning and guidance

Prostate cancer is one of the most frequently diagnosed malignancies globally and the second leading cause of cancer-related mortality in males in the developed world. In recent decades, many techniques have been proposed for prostate cancer diagnosis and treatment. With the development of imaging technologies such as CT and MRI, image-guided procedures have become increasingly important as a means to improve clinical outcomes. Analysis of the preoperative images and construction of 3D models prior to treatment would help doctors to better localize and visualize the structures of interest, plan the procedure, diagnose disease and guide the surgery or therapy. This requires efficient and robust medical image analysis and segmentation technologies to be developed. The thesis mainly focuses on the development of segmentation techniques in pelvic MRI for image-guided robotic-assisted laparoscopic radical prostatectomy and external-beam radiation therapy. A fully automated multi-atlas framework is proposed for bony pelvis segmentation in MRI, using the guidance of MRI AE-SDM. With the guidance of the AE-SDM, a multi-atlas segmentation algorithm is used to delineate the bony pelvis in a new \ac{MRI} where there is no CT available. The proposed technique outperforms state-of-the-art algorithms for MRI bony pelvis segmentation. With the SDM of pelvis and its segmented surface, an accurate 3D pelvimetry system is designed and implemented to measure a comprehensive set of pelvic geometric parameters for the examination of the relationship between these parameters and the difficulty of robotic-assisted laparoscopic radical prostatectomy. This system can be used in both manual and automated manner with a user-friendly interface. A fully automated and robust multi-atlas based segmentation has also been developed to delineate the prostate in diagnostic MR scans, which have large variation in both intensity and shape of prostate. Two image analysis techniques are proposed, including patch-based label fusion with local appearance-specific atlases and multi-atlas propagation via a manifold graph on a database of both labeled and unlabeled images when limited labeled atlases are available. The proposed techniques can achieve more robust and accurate segmentation results than other multi-atlas based methods. The seminal vesicles are also an interesting structure for therapy planning, particularly for external-beam radiation therapy. As existing methods fail for the very onerous task of segmenting the seminal vesicles, a multi-atlas learning framework via random decision forests with graph cuts refinement has further been proposed to solve this difficult problem. Motivated by the performance of this technique, I further extend the multi-atlas learning to segment the prostate fully automatically using multispectral (T1 and T2-weighted) MR images via hybrid \ac{RF} classifiers and a multi-image graph cuts technique. The proposed method compares favorably to the previously proposed multi-atlas based prostate segmentation. The work in this thesis covers different techniques for pelvic image segmentation in MRI. These techniques have been continually developed and refined, and their application to different specific problems shows ever more promising results.Open Acces