Closed and open source neuroimage analysis tools and libraries at UNC

pre-printThe emergence of open-source libraries and development tools in the last decade has changed the process of academic software development in many ways. In medical image processing and visualization this change is especially evident, also because open source projects are actively furthered by grant funding institutions. This manuscript presents the use of such development tools and libraries at the UNC Neuro-Image Analysis Laboratory for open source applications and tools. We have also experienced in our research that the development of open source in academics raises the issue of access to unpublished methodology. The strategy at our laboratory is to combine all in-house libraries and applications into a single repository that consists of two parts: a fully open source part that is distributed under a Berkley-style license and a private, closed source part with unpublished tools and methods. Access to the open source part is unrestricted, whereas the private parts can only be downloaded via cvs user login. This setup solved our issues regarding unpublished methodology, as migration from the private to the open source part is very simple. Overall our experience with this development environment within the academic setting is very positive

Statistical group differences in anatomical shape analysis using Hotelling T2 Metric

journal articleShape analysis has become of increasing interest to the neuroimaging community due to its potential to precisely locate morphological changes between healthy and pathological structures. This manuscript presents a comprehensive set of tools for the computation of 3D structural statistical shape analysis. It has been applied in several studies on brain morphometry, but can potentially be employed in other 3D shape problems. Its main limitations is the necessity of spherical topology. The input of the proposed shape analysis is a set of binary segmentation of a single brain structure, such as the hippocampus or caudate. These segmentations are converted into a corresponding spherical harmonic description (SPHARM), which is then sampled into a triangulated surfaces (SPHARM-PDM). After alignment, differences between groups of surfaces are computed using the Hotelling T2 two sample metric. Statistical pvalues, both raw and corrected for multiple comparisons, result in significance maps. Additional visualization of the group tests are provided via mean difference magnitude and vector maps, as well as maps of the group covariance information. The correction for multiple comparisons is performed via two separate methods that each have a distinct view of the problem. The first one aims to control the family-wise error rate (FWER) or false-positives via the extrema histogram of non-parametric permutations. The second method controls the false discovery rate and results in a less conservative estimate of the false-negatives. Prior versions of this shape analysis framework have been applied already to clinical studies on hippocampus and lateral ventricle shape in adult schizophrenics. The novelty of this submission is the use of the Hotelling T2 two-sample group difference metric for the computation of a template free statistical shape analysis. Template free group testing allowed this framework to become independent of any template choice, as well as it improved the sensitivity of our method considerably. In addition to our existing correction methodology for the multiple comparison problem using non-parametric permutation tests, we have extended the testing framework to include False Discovery Rate (FDR). FDR provides a significance correction with higher sensitivity while allowing a expected minimal amount of false-positives compared to our prior testing scheme

Diagnostic index: An open-source tool to classify TMJ OA condyles

Osteoarthritis (OA) of temporomandibular joints (TMJ) occurs in about 40% of the patients who present TMJ disorders. Despite its prevalence, OA diagnosis and treatment remain controversial since there are no clear symptoms of the disease, especially in early stages. Quantitative tools based on 3D imaging of the TMJ condyle have the potential to help characterize TMJ OA changes. The goals of the tools proposed in this study are to ultimately develop robust imaging markers for diagnosis and assessment of treatment efficacy. This work proposes to identify differences among asymptomatic controls and different clinical phenotypes of TMJ OA by means of Statistical Shape Modeling (SSM), obtained via clinical expert consensus. From three different grouping schemes (with 3, 5 and 7 groups), our best results reveal that that the majority (74.5%) of the classifications occur in agreement with the groups assigned by consensus between our clinical experts. Our findings suggest the existence of different disease-based phenotypic morphologies in TMJ OA. Our preliminary findings with statistical shape modeling based biomarkers may provide a quantitative staging of the disease. The methodology used in this study is included in an open source image analysis toolbox, to ensure reproducibility and appropriate distribution and dissemination of the solution proposed

Maximising the diagnostic value of structural MRI in the diagnosis of dementia: a comprehensive study of post-mortem proven cases

This thesis investigates the use of atrophy patterns from structural brain imaging to distinguish different dementia pathologies, including Alzheimer's disease, dementia with Lewy bodies and frontotemporal dementia pathologies. Using gold standard histopathology to stratify groups, analysis is based on 3D-T1-weighted imaging acquired during life in patients who attended clinic in one of three European centres. As well as comparison of disease groups with healthy controls, more clinically relevant comparisons between disease groups are performed to identify features that may be useful for differential diagnosis. The image analysis techniques used in this thesis range from simple visual assessment to more advanced machine learning. Visual rating scales were found to be reliable, quick to perform, and when used in combination, could achieve diagnostic accuracy equal to unstructured visual assessment by dementia experts. Voxel based morphometry, used to provide a comprehensive estimate of global patterns of atrophy in pathologically distinct dementias, confirmed findings in the literature based on clinical data, and identified novel regions of interest for further study. A fully automated diagnostic approach using multi-atlas segmentation propagation and support vector classifiers, revealed brain volume differences between pathologically distinct groups, yet with several technical limitations to address. Since histopathological diagnosis is rare in such a large, pathologically diverse cohort, this thesis also considers opportunities to develop the dataset into a shared resource for the dementia research community. To this end, a web application was developed to allow the data to be shared between collaborating centres, with plans to adapt this into a teaching resource. In summary, this thesis uses a variety of analysis techniques to identify imaging features that may be useful for the differential diagnosis of dementia pathologies. Various opportunities are explored to maximise the value that can be derived from this unique and valuable dataset

Summaries of plenary, symposia, and oral sessions at the XXII World Congress of Psychiatric Genetics, Copenhagen, Denmark, 12-16 October 2014

The XXII World Congress of Psychiatric Genetics, sponsored by the International Society of Psychiatric Genetics, took place in Copenhagen, Denmark, on 12-16 October 2014. A total of 883 participants gathered to discuss the latest findings in the field. The following report was written by student and postdoctoral attendees. Each was assigned one or more sessions as a rapporteur. This manuscript represents topics covered in most, but not all of the oral presentations during the conference, and contains some of the major notable new findings reported

Monitoring and predicting actions and their consequences in the human brain.

There is substantial evidence that our ability to monitor our actions is based on the use of an internal forward model that uses an efference copy of the motor command to predict the sensory consequences of an action. This prediction is used to attenuate the sensory consequences of our actions. There is accumulating evidence that our ability to understand and predict the actions of others and their consequences is based on the same systems that are involved in monitoring our own actions. This thesis describes a series of experiments investigating the neural mechanisms underlying our ability to monitor our actions and predict their sensory consequences, and our ability to understand and predict the actions of others. I describe two fMRI experiments investigating the neural mechanism underlying sensorimotor attenuation during eye-blinks. I find that the neural response to visual stimulation is actively suppressed during eye-blinks. Another two studies provide evidence that our ability to monitor the actions of others and their consequences is based on the same neural mechanisms that are involved in monitoring our own actions and predicting their sensory consequences. They also suggest that the mirror system acts in a predictive manner, anticipating the actions of others, rather than merely responding to sensory input. I also examine the possibility that, in addition to using our motor systems to understand the actions of others, we understand the sensations experienced by others by representing these sensations in our own sensory cortices. I find evidence of a touch mirror system, which responds to both the observation and experience of touch. Finally, I describe two electroencephalography experiments that shed light on the development of our ability to understand other people's actions, providing evidence for the early development and involvement of the mirror system in action observation and in predicting the sensory consequences of actions

Integrated navigation and visualisation for skull base surgery

Skull base surgery involves the management of tumours located on the underside of the brain and the base of the skull. Skull base tumours are intricately associated with several critical neurovascular structures making surgery challenging and high risk. Vestibular schwannoma (VS) is a benign nerve sheath tumour arising from one of the vestibular nerves and is the commonest pathology encountered in skull base surgery. The goal of modern VS surgery is maximal tumour removal whilst preserving neurological function and maintaining quality of life but despite advanced neurosurgical techniques, facial nerve paralysis remains a potentially devastating complication of this surgery. This thesis describes the development and integration of various advanced navigation and visualisation techniques to increase the precision and accuracy of skull base surgery. A novel Diffusion Magnetic Resonance Imaging (dMRI) acquisition and processing protocol for imaging the facial nerve in patients with VS was developed to improve delineation of facial nerve preoperatively. An automated Artificial Intelligence (AI)-based framework was developed to segment VS from MRI scans. A user-friendly navigation system capable of integrating dMRI and tractography of the facial nerve, 3D tumour segmentation and intraoperative 3D ultrasound was developed and validated using an anatomically-realistic acoustic phantom model of a head including the skull, brain and VS. The optical properties of five types of human brain tumour (meningioma, pituitary adenoma, schwannoma, low- and high-grade glioma) and nine different types of healthy brain tissue were examined across a wavelength spectrum of 400 nm to 800 nm in order to inform the development of an Intraoperative Hypserpectral Imaging (iHSI) system. Finally, functional and technical requirements of an iHSI were established and a prototype system was developed and tested in a first-in-patient study

Sensorimotor experience in virtual environments

The goal of rehabilitation is to reduce impairment and provide functional improvements resulting in quality participation in activities of life, Plasticity and motor learning principles provide inspiration for therapeutic interventions including movement repetition in a virtual reality environment, The objective of this research work was to investigate functional specific measurements (kinematic, behavioral) and neural correlates of motor experience of hand gesture activities in virtual environments stimulating sensory experience (VE) using a hand agent model. The fMRI compatible Virtual Environment Sign Language Instruction (VESLI) System was designed and developed to provide a number of rehabilitation and measurement features, to identify optimal learning conditions for individuals and to track changes in performance over time. Therapies and measurements incorporated into VESLI target and track specific impairments underlying dysfunction. The goal of improved measurement is to develop targeted interventions embedded in higher level tasks and to accurately track specific gains to understand the responses to treatment, and the impact the response may have upon higher level function such as participation in life. To further clarify the biological model of motor experiences and to understand the added value and role of virtual sensory stimulation and feedback which includes seeing one\u27s own hand movement, functional brain mapping was conducted with simultaneous kinematic analysis in healthy controls and in stroke subjects. It is believed that through the understanding of these neural activations, rehabilitation strategies advantaging the principles of plasticity and motor learning will become possible. The present research assessed successful practice conditions promoting gesture learning behavior in the individual. For the first time, functional imaging experiments mapped neural correlates of human interactions with complex virtual reality hands avatars moving synchronously with the subject\u27s own hands, Findings indicate that healthy control subjects learned intransitive gestures in virtual environments using the first and third person avatars, picture and text definitions, and while viewing visual feedback of their own hands, virtual hands avatars, and in the control condition, hidden hands. Moreover, exercise in a virtual environment with a first person avatar of hands recruited insular cortex activation over time, which might indicate that this activation has been associated with a sense of agency. Sensory augmentation in virtual environments modulated activations of important brain regions associated with action observation and action execution. Quality of the visual feedback was modulated and brain areas were identified where the amount of brain activation was positively or negatively correlated with the visual feedback, When subjects moved the right hand and saw unexpected response, the left virtual avatar hand moved, neural activation increased in the motor cortex ipsilateral to the moving hand This visual modulation might provide a helpful rehabilitation therapy for people with paralysis of the limb through visual augmentation of skills. A model was developed to study the effects of sensorimotor experience in virtual environments, and findings of the effect of sensorimotor experience in virtual environments upon brain activity and related behavioral measures. The research model represents a significant contribution to neuroscience research, and translational engineering practice, A model of neural activations correlated with kinematics and behavior can profoundly influence the delivery of rehabilitative services in the coming years by giving clinicians a framework for engaging patients in a sensorimotor environment that can optimally facilitate neural reorganization

Proceedings of the Third International Workshop on Mathematical Foundations of Computational Anatomy - Geometrical and Statistical Methods for Modelling Biological Shape Variability

International audienceComputational anatomy is an emerging discipline at the interface of geometry, statistics and image analysis which aims at modeling and analyzing the biological shape of tissues and organs. The goal is to estimate representative organ anatomies across diseases, populations, species or ages, to model the organ development across time (growth or aging), to establish their variability, and to correlate this variability information with other functional, genetic or structural information. The Mathematical Foundations of Computational Anatomy (MFCA) workshop aims at fostering the interactions between the mathematical community around shapes and the MICCAI community in view of computational anatomy applications. It targets more particularly researchers investigating the combination of statistical and geometrical aspects in the modeling of the variability of biological shapes. The workshop is a forum for the exchange of the theoretical ideas and aims at being a source of inspiration for new methodological developments in computational anatomy. A special emphasis is put on theoretical developments, applications and results being welcomed as illustrations. Following the successful rst edition of this workshop in 20061 and second edition in New-York in 20082, the third edition was held in Toronto on September 22 20113. Contributions were solicited in Riemannian and group theoretical methods, geometric measurements of the anatomy, advanced statistics on deformations and shapes, metrics for computational anatomy, statistics of surfaces, modeling of growth and longitudinal shape changes. 22 submissions were reviewed by three members of the program committee. To guaranty a high level program, 11 papers only were selected for oral presentation in 4 sessions. Two of these sessions regroups classical themes of the workshop: statistics on manifolds and diff eomorphisms for surface or longitudinal registration. One session gathers papers exploring new mathematical structures beyond Riemannian geometry while the last oral session deals with the emerging theme of statistics on graphs and trees. Finally, a poster session of 5 papers addresses more application oriented works on computational anatomy