Backwards is the way forward: feedback in the cortical hierarchy predicts the expected future

Clark offers a powerful description of the brain as a prediction machine, which offers progress on two distinct levels. First, on an abstract conceptual level, it provides a unifying framework for perception, action, and cognition (including subdivisions such as attention, expectation, and imagination). Second, hierarchical prediction offers progress on a concrete descriptive level for testing and constraining conceptual elements and mechanisms of predictive coding models (estimation of predictions, prediction errors, and internal models)

Computerized Analysis of Magnetic Resonance Images to Study Cerebral Anatomy in Developing Neonates

The study of cerebral anatomy in developing neonates is of great importance for the understanding of brain development during the early period of life. This dissertation therefore focuses on three challenges in the modelling of cerebral anatomy in neonates during brain development. The methods that have been developed all use Magnetic Resonance Images (MRI) as source data. To facilitate study of vascular development in the neonatal period, a set of image analysis algorithms are developed to automatically extract and model cerebral vessel trees. The whole process consists of cerebral vessel tracking from automatically placed seed points, vessel tree generation, and vasculature registration and matching. These algorithms have been tested on clinical Time-of- Flight (TOF) MR angiographic datasets. To facilitate study of the neonatal cortex a complete cerebral cortex segmentation and reconstruction pipeline has been developed. Segmentation of the neonatal cortex is not effectively done by existing algorithms designed for the adult brain because the contrast between grey and white matter is reversed. This causes pixels containing tissue mixtures to be incorrectly labelled by conventional methods. The neonatal cortical segmentation method that has been developed is based on a novel expectation-maximization (EM) method with explicit correction for mislabelled partial volume voxels. Based on the resulting cortical segmentation, an implicit surface evolution technique is adopted for the reconstruction of the cortex in neonates. The performance of the method is investigated by performing a detailed landmark study. To facilitate study of cortical development, a cortical surface registration algorithm for aligning the cortical surface is developed. The method first inflates extracted cortical surfaces and then performs a non-rigid surface registration using free-form deformations (FFDs) to remove residual alignment. Validation experiments using data labelled by an expert observer demonstrate that the method can capture local changes and follow the growth of specific sulcus

Underwater image restoration: super-resolution and deblurring via sparse representation and denoising by means of marine snow removal

Underwater imaging has been widely used as a tool in many fields, however, a major issue is the quality of the resulting images/videos. Due to the light's interaction with water and its constituents, the acquired underwater images/videos often suffer from a significant amount of scatter (blur, haze) and noise. In the light of these issues, this thesis considers problems of low-resolution, blurred and noisy underwater images and proposes several approaches to improve the quality of such images/video frames. Quantitative and qualitative experiments validate the success of proposed algorithms

Computer-Assisted Planning and Robotics in Epilepsy Surgery

Epilepsy is a severe and devastating condition that affects ~1% of the population. Around 30% of these patients are drug-refractory. Epilepsy surgery may provide a cure in selected individuals with drug-resistant focal epilepsy if the epileptogenic zone can be identified and safely resected or ablated. Stereoelectroencephalography (SEEG) is a diagnostic procedure that is performed to aid in the delineation of the seizure onset zone when non-invasive investigations are not sufficiently informative or discordant. Utilizing a multi-modal imaging platform, a novel computer-assisted planning (CAP) algorithm was adapted, applied and clinically validated for optimizing safe SEEG trajectory planning. In an initial retrospective validation study, 13 patients with 116 electrodes were enrolled and safety parameters between automated CAP trajectories and expert manual plans were compared. The automated CAP trajectories returned statistically significant improvements in all of the compared clinical metrics including overall risk score (CAP 0.57 +/- 0.39 (mean +/- SD) and manual 1.00 +/- 0.60, p < 0.001). Assessment of the inter-rater variability revealed there was no difference in external expert surgeon ratings. Both manual and CAP electrodes were rated as feasible in 42.8% (42/98) of cases. CAP was able to provide feasible electrodes in 19.4% (19/98), whereas manual planning was able to generate a feasible electrode in 26.5% (26/98) when the alternative generation method was not feasible. Based on the encouraging results from the retrospective analysis a prospective validation study including an additional 125 electrodes in 13 patients was then undertaken to compare CAP to expert manual plans from two neurosurgeons. The manual plans were performed separately and blindly from the CAP. Computer-generated trajectories were found to carry lower risks scores (absolute difference of 0.04 mm (95% CI = -0.42-0.01), p = 0.04) and were subsequently implanted in all cases without complication. The pipeline has been fully integrated into the clinical service and has now replaced manual SEEG planning at our institution. Further efforts were then focused on the distillation of optimal entry and target points for common SEEG trajectories and applying machine learning methods to develop an active learning algorithm to adapt to individual surgeon preferences. Thirty-two patients were prospectively enrolled in the study. The first 12 patients underwent prospective CAP planning and implantation following the pipeline outlined in the previous study. These patients were used as a training set and all of the 108 electrodes after successful implantation were normalized to atlas space to generate ‘spatial priors’, using a K-Nearest Neighbour (K-NN) classifier. A subsequent test set of 20 patients (210 electrodes) were then used to prospectively validate the spatial priors. From the test set, 78% (123/157) of the implanted trajectories passed through both the entry and target spatial priors defined from the training set. To improve the generalizability of the spatial priors to other neurosurgical centres undertaking SEEG and to take into account the potential for changing institutional practices, an active learning algorithm was implemented. The K-NN classifier was shown to dynamically learn and refine the spatial priors. The progressive refinement of CAP SEEG planning outlined in this and previous studies has culminated in an algorithm that not only optimizes the surgical heuristics and risk scores related to SEEG planning but can also learn from previous experience. Overall, safe and feasible trajectory schema were returning in 30% of the time required for manual SEEG planning. Computer-assisted planning was then applied to optimize laser interstitial thermal therapy (LITT) trajectory planning, which is a minimally invasive alternative to open mesial temporal resections, focal lesion ablation and anterior 2/3 corpus callosotomy. We describe and validate the first CAP algorithm for mesial temporal LITT ablations for epilepsy treatment. Twenty-five patients that had previously undergone LITT ablations at a single institution and with a median follow up of 2 years were included. Trajectory parameters for the CAP algorithm were derived from expert consensus to maximize distance from vasculature and ablation of the amygdalohippocampal complex, minimize collateral damage to adjacent brain structures whilst avoiding transgression of the ventricles and sulci. Trajectory parameters were also optimized to reduce the drilling angle to the skull and overall catheter length. Simulated cavities attributable to the CAP trajectories were calculated using a 5-15 mm ablation diameter. In comparison to manually planned and implemented LITT trajectories,CAP resulted in a significant increase in the percentage ablation of the amygdalohippocampal complex (manual 57.82 +/- 15.05% (mean +/- S.D.) and unablated medial hippocampal head depth (manual 4.45 +/- 1.58 mm (mean +/- S.D.), CAP 1.19 +/- 1.37 (mean +/- S.D.), p = 0.0001). As LITT ablation of the mesial temporal structures is a novel procedure there are no established standards for trajectory planning. A data-driven machine learning approach was, therefore, applied to identify hitherto unknown CAP trajectory parameter combinations. All possible combinations of planning parameters were calculated culminating in 720 unique combinations per patient. Linear regression and random forest machine learning algorithms were trained on half of the data set (3800 trajectories) and tested on the remaining unseen trajectories (3800 trajectories). The linear regression and random forest methods returned good predictive accuracies with both returning Pearson correlations of ρ = 0.7 and root mean squared errors of 0.13 and 0.12 respectively. The machine learning algorithm revealed that the optimal entry points were centred over the junction of the inferior occipital, middle temporal and middle occipital gyri. The optimal target points were anterior and medial translations of the centre of the amygdala. A large multicenter external validation study of 95 patients was then undertaken comparing the manually planned and implemented trajectories, CAP trajectories targeting the centre of the amygdala, the CAP parameters derived from expert consensus and the CAP trajectories utilizing the machine learning derived parameters. Three external blinded expert surgeons were then selected to undertake feasibility ratings and preference rankings of the trajectories. CAP generated trajectories result in a significant improvement in many of the planning metrics, notably the risk score (manual 1.3 +/- 0.1 (mean +/- S.D.), CAP 1.1 +/- 0.2 (mean +/- S.D.), p<0.000) and overall ablation of the amygdala (manual 45.3 +/- 22.2 % (mean +/- S.D.), CAP 64.2 +/- 20 % (mean +/- S.D.), p<0.000). Blinded external feasibility ratings revealed that manual trajectories were less preferable than CAP planned trajectories with an estimated probability of being ranked 4th (lowest) of 0.62. Traditional open corpus callosotomy requires a midline craniotomy, interhemispheric dissection and disconnection of the rostrum, genu and body of the corpus callosum. In cases where drop attacks persist a completion corpus callosotomy to disrupt the remaining fibres in the splenium is then performed. The emergence of LITT technology has raised the possibility of being able to undertake this procedure in a minimally invasive fashion and without the need for a craniotomy using two or three individual trajectories. Early case series have shown LITT anterior two-thirds corpus callosotomy to be safe and efficacious. Whole-brain probabilistic tractography connectomes were generated utilizing 3-Tesla multi-shell imaging data and constrained spherical deconvolution (CSD). Two independent blinded expert neurosurgeons with experience of performing the procedure using LITT then planned the trajectories in each patient following their current clinical practice. Automated trajectories returned a significant reduction in the risk score (manual 1.3 +/- 0.1 (mean +/- S.D.), CAP 1.1 +/- 0.1 (mean +/- S.D.), p<0.000). Finally, we investigate the different methods of surgical implantation for SEEG electrodes. As an initial study, a systematic review and meta-analysis of the literature to date were performed. This revealed a wide variety of implantation methods including traditional frame-based, frameless, robotic and custom-3D printed jigs were being used in clinical practice. Of concern, all comparative reports from institutions that had changed from one implantation method to another, such as following the introduction of robotic systems, did not undertake parallel-group comparisons. This suggests that patients may have been exposed to risks associated with learning curves and potential harms related to the new device until the efficacy was known. A pragmatic randomized control trial of a novel non-CE marked robotic trajectory guidance system (iSYS1) was then devised. Before clinical implantations began a series of pre-clinical investigations utilizing 3D printed phantom heads from previously implanted patients was performed to provide pilot data and also assess the surgical learning curve. The surgeons had comparatively little clinical experience with the new robotic device which replicates the introduction of such novel technologies to clinical practice. The study confirmed that the learning curve with the iSYS1 devices was minimal and the accuracies and workflow were similar to the conventional manual method. The randomized control trial represents the first of its kind for stereotactic neurosurgical procedures. Thirty-two patients were enrolled with 16 patients randomized to the iSYS1 intervention arm and 16 patients to the manual implantation arm. The intervention allocation was concealed from the patients. The surgical and research team could be not blinded. Trial management, independent data monitoring and trial steering committees were convened at four points doing the trial (after every 8 patients implanted). Based on the high level of accuracy required for both methods, the main distinguishing factor would be the time to achieve the alignment to the prespecified trajectory. The primary outcome for comparison, therefore, was the time for individual SEEG electrode implantation. Secondary outcomes included the implantation accuracy derived from the post-operative CT scan, infection, intracranial haemorrhage and neurological deficit rates. Overall, 32 patients (328 electrodes) completed the trial (16 in each intervention arm) and the baseline demographics were broadly similar between the two groups. The time for individual electrode implantation was significantly less with the iSYS1 device (median of 3.36 (95% CI 5.72 to 7.07) than for the PAD group (median of 9.06 minutes (95% CI 8.16 to 10.06), p=0.0001). Target point accuracy was significantly greater with the PAD (median of 1.58 mm (95% CI 1.38 to 1.82) compared to the iSYS1 (median of 1.16 mm (95% CI 1.01 to 1.33), p=0.004). The difference between the target point accuracies are not clinically significant for SEEG but may have implications for procedures such as deep brain stimulation that require higher placement accuracy. All of the electrodes achieved their respective intended anatomical targets. In 12 of 16 patients following robotic implantations, and 10 of 16 following manual PAD implantations a seizure onset zone was identified and resection recommended. The aforementioned systematic review and meta-analysis were updated to include additional studies published during the trial duration. In this context, the iSYS1 device entry and target point accuracies were similar to those reported in other published studies of robotic devices including the ROSA, Neuromate and iSYS1. The PAD accuracies, however, outperformed the previously published results for other frameless stereotaxy methods. In conclusion, the presented studies report the integration and validation of a complex clinical decision support software into the clinical neurosurgical workflow for SEEG planning. The stereotactic planning platform was further refined by integrating machine learning techniques and also extended towards optimisation of LITT trajectories for ablation of mesial temporal structures and corpus callosotomy. The platform was then used to seamlessly integrate with a novel trajectory planning software to effectively and safely guide the implantation of the SEEG electrodes. Through a single-blinded randomised control trial, the ISYS1 device was shown to reduce the time taken for individual electrode insertion. Taken together, this work presents and validates the first fully integrated stereotactic trajectory planning platform that can be used for both SEEG and LITT trajectory planning followed by surgical implantation through the use of a novel trajectory guidance system

Data-Driven Image Restoration

Every day many images are taken by digital cameras, and people are demanding visually accurate and pleasing result. Noise and blur degrade images captured by modern cameras, and high-level vision tasks (such as segmentation, recognition, and tracking) require high-quality images. Therefore, image restoration specifically, image deblurring and image denoising is a critical preprocessing step. A fundamental problem in image deblurring is to recover reliably distinct spatial frequencies that have been suppressed by the blur kernel. Existing image deblurring techniques often rely on generic image priors that only help recover part of the frequency spectrum, such as the frequencies near the high-end. To this end, we pose the following specific questions: (i) Does class-specific information offer an advantage over existing generic priors for image quality restoration? (ii) If a class-specific prior exists, how should it be encoded into a deblurring framework to recover attenuated image frequencies? Throughout this work, we devise a class-specific prior based on the band-pass filter responses and incorporate it into a deblurring strategy. Specifically, we show that the subspace of band-pass filtered images and their intensity distributions serve as useful priors for recovering image frequencies. Next, we present a novel image denoising algorithm that uses external, category specific image database. In contrast to existing noisy image restoration algorithms, our method selects clean image “support patches” similar to the noisy patch from an external database. We employ a content adaptive distribution model for each patch where we derive the parameters of the distribution from the support patches. Our objective function composed of a Gaussian fidelity term that imposes category specific information, and a low-rank term that encourages the similarity between the noisy and the support patches in a robust manner. Finally, we propose to learn a fully-convolutional network model that consists of a Chain of Identity Mapping Modules (CIMM) for image denoising. The CIMM structure possesses two distinctive features that are important for the noise removal task. Firstly, each residual unit employs identity mappings as the skip connections and receives pre-activated input to preserve the gradient magnitude propagated in both the forward and backward directions. Secondly, by utilizing dilated kernels for the convolution layers in the residual branch, each neuron in the last convolution layer of each module can observe the full receptive field of the first layer

Biostatistical modeling and analysis of combined fMRI and EEG measurements

The purpose of brain mapping is to advance the understanding of the relationship between structure and function in the human brain. Several techniques---with different advantages and disadvantages---exist for recording neural activity. Functional magnetic resonance imaging (fMRI) has a high spatial resolution, but low temporal resolution. It also suffers from a low-signal-to-noise ratio in event-related experimental designs, which are commonly used to investigate neuronal brain activity. On the other hand, the high temporal resolution of electroencephalography (EEG) recordings allows to capture provoked event-related potentials. Though, 3D maps derived by EEG source reconstruction methods have a low spatial resolution, they provide complementary information about the location of neuronal activity. There is a strong interest in combining data from both modalities to gain a deeper knowledge of brain functioning through advanced statistical modeling. In this thesis, a new Bayesian method is proposed for enhancing fMRI activation detection by the use of EEG-based spatial prior information in stimulus based experimental paradigms. This method builds upon a newly developed mere fMRI activation detection method. In general, activation detection corresponds to stimulus predictor components having an effect on the fMRI signal trajectory in a voxelwise linear model. We model and analyze stimulus influence by a spatial Bayesian variable selection scheme, and extend existing high-dimensional regression methods by incorporating prior information on binary selection indicators via a latent probit regression. For mere fMRI activation detection, the predictor consists of a spatially-varying intercept only. For EEG-enhanced schemes, an EEG effect is added, which is either chosen to be spatially-varying or constant. Spatially-varying effects are regularized by different Markov random field priors. Statistical inference in resulting high-dimensional hierarchical models becomes rather challenging from a modeling perspective as well as with regard to numerical issues. In this thesis, inference is based on a Markov Chain Monte Carlo (MCMC) approach relying on global updates of effect maps. Additionally, a faster algorithm is developed based on single-site updates to circumvent the computationally intensive, high-dimensional, sparse Cholesky decompositions. The proposed algorithms are examined in both simulation studies and real-world applications. Performance is evaluated in terms of convergency properties, the ability to produce interpretable results, and the sensitivity and specificity of corresponding activation classification rules. The main question is whether the use of EEG information can increase the power of fMRI models to detect activated voxels. In summary, the new algorithms show a substantial increase in sensitivity compared to existing fMRI activation detection methods like classical SPM. Carefully selected EEG-prior information additionally increases sensitivity in activation regions that have been distorted by a low signal-to-noise ratio

Doctor of Philosophy

dissertationImage segmentation entails the partitioning of an image domain, usually two or three dimensions, so that each partition or segment has some meaning that is relevant to the application at hand. Accurate image segmentation is a crucial challenge in many disciplines, including medicine, computer vision, and geology. In some applications, heterogeneous pixel intensities; noisy, ill-defined, or diffusive boundaries; and irregular shapes with high variability can make it challenging to meet accuracy requirements. Various segmentation approaches tackle such challenges by casting the segmentation problem as an energy-minimization problem, and solving it using efficient optimization algorithms. These approaches are broadly classified as either region-based or edge (surface)-based depending on the features on which they operate. The focus of this dissertation is on the development of a surface-based energy model, the design of efficient formulations of optimization frameworks to incorporate such energy, and the solution of the energy-minimization problem using graph cuts. This dissertation utilizes a set of four papers whose motivation is the efficient extraction of the left atrium wall from the late gadolinium enhancement magnetic resonance imaging (LGE-MRI) image volume. This dissertation utilizes these energy formulations for other applications, including contact lens segmentation in the optical coherence tomography (OCT) data and the extraction of geologic features in seismic data. Chapters 2 through 5 (papers 1 through 4) explore building a surface-based image segmentation model by progressively adding components to improve its accuracy and robustness. The first paper defines a parametric search space and its discrete formulation in the form of a multilayer three-dimensional mesh model within which the segmentation takes place. It includes a generative intensity model, and we optimize using a graph formulation of the surface net problem. The second paper proposes a Bayesian framework with a Markov random field (MRF) prior that gives rise to another class of surface nets, which provides better segmentation with smooth boundaries. The third paper presents a maximum a posteriori (MAP)-based surface estimation framework that relies on a generative image model by incorporating global shape priors, in addition to the MRF, within the Bayesian formulation. Thus, the resulting surface not only depends on the learned model of shapes,but also accommodates the test data irregularities through smooth deviations from these priors. Further, the paper proposes a new shape parameter estimation scheme, in closed form, for segmentation as a part of the optimization process. Finally, the fourth paper (under review at the time of this document) presents an extensive analysis of the MAP framework and presents improved mesh generation and generative intensity models. It also performs a thorough analysis of the segmentation results that demonstrates the effectiveness of the proposed method qualitatively, quantitatively, and clinically. Chapter 6, consisting of unpublished work, demonstrates the application of an MRF-based Bayesian framework to segment coupled surfaces of contact lenses in optical coherence tomography images. This chapter also shows an application related to the extraction of geological structures in seismic volumes. Due to the large sizes of seismic volume datasets, we also present fast, approximate surface-based energy minimization strategies that achieve better speed-ups and memory consumption

Development of an Atlas-Based Segmentation of Cranial Nerves Using Shape-Aware Discrete Deformable Models for Neurosurgical Planning and Simulation

Twelve pairs of cranial nerves arise from the brain or brainstem and control our sensory functions such as vision, hearing, smell and taste as well as several motor functions to the head and neck including facial expressions and eye movement. Often, these cranial nerves are difficult to detect in MRI data, and thus represent problems in neurosurgery planning and simulation, due to their thin anatomical structure, in the face of low imaging resolution as well as image artifacts. As a result, they may be at risk in neurosurgical procedures around the skull base, which might have dire consequences such as the loss of eyesight or hearing and facial paralysis. Consequently, it is of great importance to clearly delineate cranial nerves in medical images for avoidance in the planning of neurosurgical procedures and for targeting in the treatment of cranial nerve disorders. In this research, we propose to develop a digital atlas methodology that will be used to segment the cranial nerves from patient image data. The atlas will be created from high-resolution MRI data based on a discrete deformable contour model called 1-Simplex mesh. Each of the cranial nerves will be modeled using its centerline and radius information where the centerline is estimated in a semi-automatic approach by finding a shortest path between two user-defined end points. The cranial nerve atlas is then made more robust by integrating a Statistical Shape Model so that the atlas can identify and segment nerves from images characterized by artifacts or low resolution. To the best of our knowledge, no such digital atlas methodology exists for segmenting nerves cranial nerves from MRI data. Therefore, our proposed system has important benefits to the neurosurgical community