Ultrasound imaging system combined with multi-modality image analysis algorithms to monitor changes in anatomical structures

This dissertation concerns the development and validation of an ultrasound imaging system and novel image analysis algorithms applicable to multiple imaging modalities. The ultrasound imaging system will include a framework for 3D volume reconstruction of freehand ultrasound: a mechanism to register the 3D volumes across time and subjects, as well as with other imaging modalities, and a playback mechanism to view image slices concurrently from different acquisitions that correspond to the same anatomical region. The novel image analysis algorithms include a noise reduction method that clusters pixels into homogenous patches using a directed graph of edges between neighboring pixels, a segmentation method that creates a hierarchical graph structure using statistical analysis and a voting system to determine the similarity between homogeneous patches given their neighborhood, and finally, a hybrid atlas-based registration method that makes use of intensity corrections induced at anatomical landmarks to regulate deformable registration. The combination of the ultrasound imaging system and the image analysis algorithms will provide the ability to monitor nerve regeneration in patients undergoing regenerative, repair or transplant strategies in a sequential, non-invasive manner, including visualization of registered real-time and pre-acquired data, thus enabling preventive and therapeutic strategies for nerve regeneration in Composite Tissue Allotransplantation (CTA). The registration algorithm is also applied to MR images of the brain to obtain reliable and efficient segmentation of the hippocampus, which is a prominent structure in the study of diseases of the elderly such as vascular dementia, Alzheimer’s, and late life depression. Experimental results on 2D and 3D images, including simulated and real images, with illustrations visualizing the intermediate outcomes and the final results are presented.

Artificial Light at Night Disrupts Pain Behavior and Cerebrovascular Structure in Mice

Artificial Light at Night Disrupts Pain Behavior and Cerebrovascular Structure in Mice Jacob R. Bumgarner Circadian rhythms are intrinsic biological processes that fluctuate in function with a period of approximately 24 hours. These rhythms are precisely synchronized to the 24- hour day of the Earth by external rhythmic signaling cues. Solar light-dark cycles are the most potent environmental signaling cue for terrestrial organisms to align internal rhythms with the external day. Proper alignment and synchrony of internal circadian rhythms with external environmental rhythms are essential for health and optimal biological function. The modern human environment on Earth is no longer conducive to properly aligned circadian rhythms. Following the industrial revolution, artificial lighting and an ever-growing 24-hour global economy have shifted humans away from natural environments suited for rhythmic behavior and physiology. Humans, and much of the natural environment, are routinely exposed to circadian rhythm disruptors. The most pervasive disruptor of circadian rhythms is artificial light at night (ALAN). A growing 80% of humans on Earth are exposed to ALAN beyond natural nighttime environmental lighting levels. ALAN exposure is associated with numerous negative consequences on behavior and physiology, including neuroinflammation, cardiovascular disease, and altered immune function. This dissertation examines two previously uninvestigated effects of ALAN exposure on physiology and behavior in mice. In Part 1, I investigated the effects of ALAN exposure on pain behavior in mice. I observed that ALAN exposure had detrimental effects on rodent pain behavior in contexts of both health and models of human disease. ALAN exposure heightened responsiveness to noxious cold stimuli and innocuous mechanical touch. Differences in these effects were noted based on sex and disease state. I conclude this section with a report on the mechanisms by which ALAN exposure altered pain behavior. In Part 2, I investigated the effects of ALAN exposure on cerebrovascular structure in mice. To conduct these investigations, I first developed VesselVio, an open-source application for the analysis and visualization of vasculature datasets. Using this application and additional analytical frameworks, I examined the effects of short-term ALAN exposure on hippocampal vasculature in mice. ALAN exposure reduced hippocampal vascular density in mice, with notable regional sex differences. I also observed that ALAN exposure altered hippocampal vascular network connectivity and structure, with persistent regional sex differences. The data in this dissertation contribute to the ever-growing field of circadian rhythm biology focused on studying circadian rhythm disruption. These data highlight the continuing need to mitigate the pervasiveness of ALAN in human and natural environments. Most importantly, the results presented in this dissertation emphasize the need to consider ALAN as a mitigating factor for the treatment of both cardiovascular disease and pain

Fetal Brain Tissue Annotation and Segmentation Challenge Results

In-utero fetal MRI is emerging as an important tool in the diagnosis and analysis of the developing human brain. Automatic segmentation of the developing fetal brain is a vital step in the quantitative analysis of prenatal neurodevelopment both in the research and clinical context. However, manual segmentation of cerebral structures is time-consuming and prone to error and inter-observer variability. Therefore, we organized the Fetal Tissue Annotation (FeTA) Challenge in 2021 in order to encourage the development of automatic segmentation algorithms on an international level. The challenge utilized FeTA Dataset, an open dataset of fetal brain MRI reconstructions segmented into seven different tissues (external cerebrospinal fluid, grey matter, white matter, ventricles, cerebellum, brainstem, deep grey matter). 20 international teams participated in this challenge, submitting a total of 21 algorithms for evaluation. In this paper, we provide a detailed analysis of the results from both a technical and clinical perspective. All participants relied on deep learning methods, mainly U-Nets, with some variability present in the network architecture, optimization, and image pre- and post-processing. The majority of teams used existing medical imaging deep learning frameworks. The main differences between the submissions were the fine tuning done during training, and the specific pre- and post-processing steps performed. The challenge results showed that almost all submissions performed similarly. Four of the top five teams used ensemble learning methods. However, one team's algorithm performed significantly superior to the other submissions, and consisted of an asymmetrical U-Net network architecture. This paper provides a first of its kind benchmark for future automatic multi-tissue segmentation algorithms for the developing human brain in utero.Comment: Results from FeTA Challenge 2021, held at MICCAI; Manuscript submitte

A non-invasive human-machine interfacing framework for investigating dexterous control of hand muscles

The recent fast development of virtual reality and robotic assistive devices enables to augment the capabilities of able-body individuals as well as to overcome the motor missing functions of neurologically impaired or amputee individuals. To control these devices, movement intentions can be captured from biological structures involved in the process of motor planning and execution, such as the central nervous system (CNS), the peripheral nervous system (in particular the spinal motor neurons) and the musculoskeletal system. Thus, human-machine interfaces (HMI) enable to transfer neural information from the neuro-muscular system to machines. To prevent any risks due to surgical operations or tissue damage in implementing these HMIs, a non-invasive approach is proposed in this thesis. In the last five decades, surface electromyography (sEMG) has been extensively explored as a non-invasive source of neural information. EMG signals are constituted by the mixed electrical activity of several recruited motor units, the fundamental components of muscle contraction. High-density sEMG (HD-sEMG) with the use of blind source separation methods enabled to identify the discharge patterns of many of these active motor units. From these decomposed discharge patterns, the net common synaptic input (CSI) to the corresponding spinal motor neurons was quantified with cross-correlation in the time and frequency domain or with principal component analysis (PCA) on one or few muscles. It has been hypothesised that this CSI would result from the contribution of spinal descending commands sent by supra-spinal structures and afferences integrated by spinal interneurons. Another motor strategy implying the integration of descending commands at the spinal level is the one regarding the coordination of many muscles to control a large number of articular joints. This neurophysiological mechanism was investigated by measuring a single EMG amplitude per muscle, thus without the use of HD-sEMG and decomposition. In this case, the aim was to understand how the central nervous system (CNS) could control a large set of muscles actuating a vast set of combinations of degrees of freedom in a modular way. Thus, time-invariant patterns of muscle coordination, i.e. muscle synergies , were found in animals and humans from EMG amplitude of many muscles, modulated by time-varying commands to be combined to fulfil complex movements. In this thesis, for the first time, we present a non-invasive framework for human-machine interfaces based on both spinal motor neuron recruitment strategy and muscle synergistic control for unifying the understanding of these two motor control strategies and producing control signals correlated to biomechanical quantities. This implies recording both from many muscles and using HD-sEMG for each muscle. We investigated 14 muscles of the hand, 6 extrinsic and 8 intrinsic. The first two studies, (in Chapters 2 and 3, respectively) present the framework for CSI quantification by PCA and the extraction of the synergistic organisation of spinal motor neurons innervating the 14 investigated muscles. For the latter analysis, in Chapter 3, we proposed the existence of what we named as motor neuron synergies extracted with non-negative matrix factorisation (NMF) from the identified motor neurons. In these first two studies, we considered 7 subjects and 7 grip types involving differently all the four fingers in opposition with the thumb. In the first study, we found that the variance explained by the CSI among all motor neuron spike trains was (53.0 ± 10.9) % and its cross-correlation with force was 0.67 ± 0.10, remarkably high with respect to previous findings. In the second study, 4 motor neuron synergies were identified and associated with the actuation of one finger in opposition with the thumb, finding even higher correlation values with force (over 0.8) for each synergy associated with a finger during the actuation of the relative finger. In Chapter 4, we then extended the set of analysed movements in a vast repertoire of gestures and repeated the analysis of Chapter 3 by finding a different synergistic organisation during the execution of tens of tasks. We divided the contribution among extrinsic and intrinsic muscles and we found that intrinsic better enable single-finger spatial discrimination, while no difference was found in regression of joint angles by dividing the two groups of muscles. Finally, in Chapter 5 we proposed the techniques of the previous chapters for cases of impairment due both to amputation and stroke. We analysed one case of pre and post rehabilitation sessions of a trans-humeral amputee, the case of a post-stroke trans-radial amputee and three cases of acute stroke, i.e. less than one month from the stroke event. We present future perspectives (Chapter 6) aimed to design and implement a platform for both rehabilitation monitoring and myoelectric control. Thus, this thesis provides a bridge between two extensively studied motor control mechanisms, i.e. motor neuron recruitment and muscle synergies, and proposes this framework as suitable for rehabilitation monitoring and control of assistive devices.Open Acces