302 research outputs found

    The 5th International Conference on Biomedical Engineering and Biotechnology (ICBEB 2016)

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    Automatic \u3csup\u3e13\u3c/sup\u3eC Chemical Shift Reference Correction of Protein NMR Spectral Data Using Data Mining and Bayesian Statistical Modeling

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    Nuclear magnetic resonance (NMR) is a highly versatile analytical technique for studying molecular configuration, conformation, and dynamics, especially of biomacromolecules such as proteins. However, due to the intrinsic properties of NMR experiments, results from the NMR instruments require a refencing step before the down-the-line analysis. Poor chemical shift referencing, especially for 13C in protein Nuclear Magnetic Resonance (NMR) experiments, fundamentally limits and even prevents effective study of biomacromolecules via NMR. There is no available method that can rereference carbon chemical shifts from protein NMR without secondary experimental information such as structure or resonance assignment. To solve this problem, we constructed a Bayesian probabilistic framework that circumvents the limitations of previous reference correction methods that required protein resonance assignment and/or three-dimensional protein structure. Our algorithm named Bayesian Model Optimized Reference Correction (BaMORC) can detect and correct 13C chemical shift referencing errors before the protein resonance assignment step of analysis and without a three-dimensional structure. By combining the BaMORC methodology with a new intra-peaklist grouping algorithm, we created a combined method called Unassigned BaMORC that utilizes only unassigned experimental peak lists and the amino acid sequence. Unassigned BaMORC kept all experimental three-dimensional HN(CO)CACB-type peak lists tested within ± 0.4 ppm of the correct 13C reference value. On a much larger unassigned chemical shift test set, the base method kept 13C chemical shift referencing errors to within ± 0.45 ppm at a 90% confidence interval. With chemical shift assignments, Assigned BaMORC can detect and correct 13C chemical shift referencing errors to within ± 0.22 at a 90% confidence interval. Therefore, Unassigned BaMORC can correct 13C chemical shift referencing errors when it will have the most impact, right before protein resonance assignment and other downstream analyses are started. After assignment, chemical shift reference correction can be further refined with Assigned BaMORC. To further support a broader usage of these new methods, we also created a software package with web-based interface for the NMR community. This software will allow non-NMR experts to detect and correct 13C referencing errors at critical early data analysis steps, lowering the bar of NMR expertise required for effective protein NMR analysis

    Recalage préservant la topologie des vaisseaux: application à la cardiologie interventionnelle

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    In percutaneous coronary interventions, integrating into the live fluoroscopic image vessel calcifications and occlusion information that are revealed in the pre-operative Computed Tomography Angiography can greatly improve guidance of the clinician. Fusing pre- and intra-operative information into a single space aims at taking advantage of two complementary modalities and requires a step of registration that must provide good alignment and relevant correspondences between them. Most of the existing 3D/2D vessel registration algorithms do not take into account the particular topology of the vasculature to be matched, resulting into pairings that may be topologically inconsistent along the vasculature.A first contribution consisted in a registration framework dedicated to curve matching, denoted the Iterative Closest Curve (ICC). Its main feature is to preserve the topological consistency along curves by taking advantage of the Frechet distance that not only computes the distance between two curves but also builds ordered pairings along them. A second contribution is a pairing procedure designed for the matching of a vascular tree structure that endorses its particular topology and that can easily take advantage of the ICC-framework. Centerlines of the 3D tree are matched to curves extracted from the 2D vascular graph while preserving the connectivity at 3D bifurcations. The matching criterion used to build the pairings takes into account the geometric distance and the resemblance between curves both based on a global formulation using the Frechet distance.To evaluate our approach we run experiments on a database composed of 63 clinical cases, measuring accuracy on real conditions and robustness with respect to a simulated displacement. Quantitative results have been obtained using two complementary measures that aim at assessing the results both geometrically and topologically, and quantify the resulting alignment error as well as the pairing error. The proposed method exhibits good results both in terms of pairing and alignment and demonstrates to be low sensitive to the rotations to be compensated (up to 30 degrees).Cette thĂšse s’inscrit dans le cadre de la cardiologie interventionnelle. IntĂ©grer des informations telles que la position des calcifications ainsi que la taille et forme d’une occlusion dans les images fluoroscopiques constituerait un bĂ©nĂ©fice pour le praticien. Ces informations, invisibles dans les images rayons-X pendant la procĂ©dure, sont prĂ©sentes au sein du scanner CT prĂ©opĂ©ratoire. La fusion de cette modalitĂ© avec la fluoroscopie apporterait une aide prĂ©cieuse au guidage temps rĂ©el des outils interventionnels en bĂ©nĂ©ficiant des informations fournies par le CT. Cette fusion requiert une Ă©tape de recalage qui vise Ă  aligner au mieux les deux modalitĂ©s et fournir des correspondances pertinentes entre elles. La plupart des algorithmes de recalage 3D/2D de vaisseaux rencontrent des difficultĂ©s Ă  construire des appariements anatomiquement pertinents, essentiellement Ă  cause du manque de cohĂ©rence topologique le long du rĂ©seau vasculaire.Afin de rĂ©soudre ce problĂšme, nous proposons dans cette thĂšse un cadre gĂ©nĂ©rique pour le recalage de structures curvilinĂ©aires. L’algorithme qui en dĂ©coule prĂ©serve la structure des courbes appariĂ©es. Les artĂšres coronaires pouvant ĂȘtre reprĂ©sentĂ©es par un ensemble de courbes arrangĂ©es en arbre, nous proposons aussi une procĂ©dure d’appariement qui respecte cette structure. Le recalage d’un arbre 3D sur un graphe 2D est ainsi rĂ©alisĂ© en assurant la prĂ©servation des connectivitĂ©s aux bifurcations. Le choix de l’appariement est basĂ© sur un critĂšre prenant en compte la distance gĂ©omĂ©trique ainsi que la ressemblance entre courbes. Ce critĂšre est Ă©valuĂ© grĂące Ă  une forme modifiĂ©e de la distance de FrĂ©chet.Une base de donnĂ©es de 63 cas cliniques a Ă©tĂ© utilisĂ©e Ă  travers diffĂ©rentes expĂ©riences afin de prouver la robustesse et la prĂ©cision de notre approche. Nous avons proposĂ© deux mesures complĂ©mentaires visant Ă  quantifier la qualitĂ© de l’alignement d’une part et des appariements engendrĂ©s d’autre part. La mĂ©thode proposĂ©e se montre prĂ©cise pour les alignements de la projection du modĂšle CT et des artĂšres coronaires observĂ©es dans les images angiographiques. De plus, les appariements obtenus sont anatomiquement pertinents et lĂĄlgorithme a prouvĂ© sa robustesse face aux perturbations de la position initiale. Nous attribuons cette robustesse Ă  la qualitĂ© des appariements construits au fur et Ă  mesure des itĂ©rations

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

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    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

    Computer-Assisted Planning and Robotics in Epilepsy Surgery

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    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

    Inferring Geodesic Cerebrovascular Graphs: Image Processing, Topological Alignment and Biomarkers Extraction

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    A vectorial representation of the vascular network that embodies quantitative features - location, direction, scale, and bifurcations - has many potential neuro-vascular applications. Patient-specific models support computer-assisted surgical procedures in neurovascular interventions, while analyses on multiple subjects are essential for group-level studies on which clinical prediction and therapeutic inference ultimately depend. This first motivated the development of a variety of methods to segment the cerebrovascular system. Nonetheless, a number of limitations, ranging from data-driven inhomogeneities, the anatomical intra- and inter-subject variability, the lack of exhaustive ground-truth, the need for operator-dependent processing pipelines, and the highly non-linear vascular domain, still make the automatic inference of the cerebrovascular topology an open problem. In this thesis, brain vessels’ topology is inferred by focusing on their connectedness. With a novel framework, the brain vasculature is recovered from 3D angiographies by solving a connectivity-optimised anisotropic level-set over a voxel-wise tensor field representing the orientation of the underlying vasculature. Assuming vessels joining by minimal paths, a connectivity paradigm is formulated to automatically determine the vascular topology as an over-connected geodesic graph. Ultimately, deep-brain vascular structures are extracted with geodesic minimum spanning trees. The inferred topologies are then aligned with similar ones for labelling and propagating information over a non-linear vectorial domain, where the branching pattern of a set of vessels transcends a subject-specific quantized grid. Using a multi-source embedding of a vascular graph, the pairwise registration of topologies is performed with the state-of-the-art graph matching techniques employed in computer vision. Functional biomarkers are determined over the neurovascular graphs with two complementary approaches. Efficient approximations of blood flow and pressure drop account for autoregulation and compensation mechanisms in the whole network in presence of perturbations, using lumped-parameters analog-equivalents from clinical angiographies. Also, a localised NURBS-based parametrisation of bifurcations is introduced to model fluid-solid interactions by means of hemodynamic simulations using an isogeometric analysis framework, where both geometry and solution profile at the interface share the same homogeneous domain. Experimental results on synthetic and clinical angiographies validated the proposed formulations. Perspectives and future works are discussed for the group-wise alignment of cerebrovascular topologies over a population, towards defining cerebrovascular atlases, and for further topological optimisation strategies and risk prediction models for therapeutic inference. Most of the algorithms presented in this work are available as part of the open-source package VTrails

    Automatic Spatiotemporal Analysis of Cardiac Image Series

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    RÉSUMÉ À ce jour, les maladies cardiovasculaires demeurent au premier rang des principales causes de dĂ©cĂšs en AmĂ©rique du Nord. Chez l’adulte et au sein de populations de plus en plus jeunes, la soi-disant Ă©pidĂ©mie d’obĂ©sitĂ© entraĂźnĂ©e par certaines habitudes de vie tels que la mauvaise alimentation, le manque d’exercice et le tabagisme est lourde de consĂ©quences pour les personnes affectĂ©es, mais aussi sur le systĂšme de santĂ©. La principale cause de morbiditĂ© et de mortalitĂ© chez ces patients est l’athĂ©rosclĂ©rose, une accumulation de plaque Ă  l’intĂ©rieur des vaisseaux sanguins Ă  hautes pressions telles que les artĂšres coronaires. Les lĂ©sions athĂ©rosclĂ©rotiques peuvent entraĂźner l’ischĂ©mie en bloquant la circulation sanguine et/ou en provoquant une thrombose. Cela mĂšne souvent Ă  de graves consĂ©quences telles qu’un infarctus. Outre les problĂšmes liĂ©s Ă  la stĂ©nose, les parois artĂ©rielles des rĂ©gions criblĂ©es de plaque augmentent la rigiditĂ© des parois vasculaires, ce qui peut aggraver la condition du patient. Dans la population pĂ©diatrique, la pathologie cardiovasculaire acquise la plus frĂ©quente est la maladie de Kawasaki. Il s’agit d’une vasculite aigĂŒe pouvant affecter l’intĂ©gritĂ© structurale des parois des artĂšres coronaires et mener Ă  la formation d’anĂ©vrismes. Dans certains cas, ceux-ci entravent l’hĂ©modynamie artĂ©rielle en engendrant une perfusion myocardique insuffisante et en activant la formation de thromboses. Le diagnostic de ces deux maladies coronariennes sont traditionnellement effectuĂ©s Ă  l’aide d’angiographies par fluoroscopie. Pendant ces examens paracliniques, plusieurs centaines de projections radiographiques sont acquises en sĂ©ries suite Ă  l’infusion artĂ©rielle d’un agent de contraste. Ces images rĂ©vĂšlent la lumiĂšre des vaisseaux sanguins et la prĂ©sence de lĂ©sions potentiellement pathologiques, s’il y a lieu. Parce que les sĂ©ries acquises contiennent de l’information trĂšs dynamique en termes de mouvement du patient volontaire et involontaire (ex. battements cardiaques, respiration et dĂ©placement d’organes), le clinicien base gĂ©nĂ©ralement son interprĂ©tation sur une seule image angiographique oĂč des mesures gĂ©omĂ©triques sont effectuĂ©es manuellement ou semi-automatiquement par un technicien en radiologie. Bien que l’angiographie par fluoroscopie soit frĂ©quemment utilisĂ© partout dans le monde et souvent considĂ©rĂ© comme l’outil de diagnostic “gold-standard” pour de nombreuses maladies vasculaires, la nature bidimensionnelle de cette modalitĂ© d’imagerie est malheureusement trĂšs limitante en termes de spĂ©cification gĂ©omĂ©trique des diffĂ©rentes rĂ©gions pathologiques. En effet, la structure tridimensionnelle des stĂ©noses et des anĂ©vrismes ne peut pas ĂȘtre pleinement apprĂ©ciĂ©e en 2D car les caractĂ©ristiques observĂ©es varient selon la configuration angulaire de l’imageur. De plus, la prĂ©sence de lĂ©sions affectant les artĂšres coronaires peut ne pas reflĂ©ter la vĂ©ritable santĂ© du myocarde, car des mĂ©canismes compensatoires naturels (ex. vaisseaux----------ABSTRACT Cardiovascular disease continues to be the leading cause of death in North America. In adult and, alarmingly, ever younger populations, the so-called obesity epidemic largely driven by lifestyle factors that include poor diet, lack of exercise and smoking, incurs enormous stresses on the healthcare system. The primary cause of serious morbidity and mortality for these patients is atherosclerosis, the build up of plaque inside high pressure vessels like the coronary arteries. These lesions can lead to ischemic disease and may progress to precarious blood flow blockage or thrombosis, often with infarction or other severe consequences. Besides the stenosis-related outcomes, the arterial walls of plaque-ridden regions manifest increased stiffness, which may exacerbate negative patient prognosis. In pediatric populations, the most prevalent acquired cardiovascular pathology is Kawasaki disease. This acute vasculitis may affect the structural integrity of coronary artery walls and progress to aneurysmal lesions. These can hinder the blood flow’s hemodynamics, leading to inadequate downstream perfusion, and may activate thrombus formation which may lead to precarious prognosis. Diagnosing these two prominent coronary artery diseases is traditionally performed using fluoroscopic angiography. Several hundred serial x-ray projections are acquired during selective arterial infusion of a radiodense contrast agent, which reveals the vessels’ luminal area and possible pathological lesions. The acquired series contain highly dynamic information on voluntary and involuntary patient movement: respiration, organ displacement and heartbeat, for example. Current clinical analysis is largely limited to a single angiographic image where geometrical measures will be performed manually or semi-automatically by a radiological technician. Although widely used around the world and generally considered the gold-standard diagnosis tool for many vascular diseases, the two-dimensional nature of this imaging modality is limiting in terms of specifying the geometry of various pathological regions. Indeed, the 3D structures of stenotic or aneurysmal lesions may not be fully appreciated in 2D because their observable features are dependent on the angular configuration of the imaging gantry. Furthermore, the presence of lesions in the coronary arteries may not reflect the true health of the myocardium, as natural compensatory mechanisms may obviate the need for further intervention. In light of this, cardiac magnetic resonance perfusion imaging is increasingly gaining attention and clinical implementation, as it offers a direct assessment of myocardial tissue viability following infarction or suspected coronary artery disease. This type of modality is plagued, however, by motion similar to that present in fluoroscopic imaging. This issue predisposes clinicians to laborious manual intervention in order to align anatomical structures in sequential perfusion frames, thus hindering automation o

    Computational methods for the analysis of functional 4D-CT chest images.

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    Medical imaging is an important emerging technology that has been intensively used in the last few decades for disease diagnosis and monitoring as well as for the assessment of treatment effectiveness. Medical images provide a very large amount of valuable information that is too huge to be exploited by radiologists and physicians. Therefore, the design of computer-aided diagnostic (CAD) system, which can be used as an assistive tool for the medical community, is of a great importance. This dissertation deals with the development of a complete CAD system for lung cancer patients, which remains the leading cause of cancer-related death in the USA. In 2014, there were approximately 224,210 new cases of lung cancer and 159,260 related deaths. The process begins with the detection of lung cancer which is detected through the diagnosis of lung nodules (a manifestation of lung cancer). These nodules are approximately spherical regions of primarily high density tissue that are visible in computed tomography (CT) images of the lung. The treatment of these lung cancer nodules is complex, nearly 70% of lung cancer patients require radiation therapy as part of their treatment. Radiation-induced lung injury is a limiting toxicity that may decrease cure rates and increase morbidity and mortality treatment. By finding ways to accurately detect, at early stage, and hence prevent lung injury, it will have significant positive consequences for lung cancer patients. The ultimate goal of this dissertation is to develop a clinically usable CAD system that can improve the sensitivity and specificity of early detection of radiation-induced lung injury based on the hypotheses that radiated lung tissues may get affected and suffer decrease of their functionality as a side effect of radiation therapy treatment. These hypotheses have been validated by demonstrating that automatic segmentation of the lung regions and registration of consecutive respiratory phases to estimate their elasticity, ventilation, and texture features to provide discriminatory descriptors that can be used for early detection of radiation-induced lung injury. The proposed methodologies will lead to novel indexes for distinguishing normal/healthy and injured lung tissues in clinical decision-making. To achieve this goal, a CAD system for accurate detection of radiation-induced lung injury that requires three basic components has been developed. These components are the lung fields segmentation, lung registration, and features extraction and tissue classification. This dissertation starts with an exploration of the available medical imaging modalities to present the importance of medical imaging in today’s clinical applications. Secondly, the methodologies, challenges, and limitations of recent CAD systems for lung cancer detection are covered. This is followed by introducing an accurate segmentation methodology of the lung parenchyma with the focus of pathological lungs to extract the volume of interest (VOI) to be analyzed for potential existence of lung injuries stemmed from the radiation therapy. After the segmentation of the VOI, a lung registration framework is introduced to perform a crucial and important step that ensures the co-alignment of the intra-patient scans. This step eliminates the effects of orientation differences, motion, breathing, heart beats, and differences in scanning parameters to be able to accurately extract the functionality features for the lung fields. The developed registration framework also helps in the evaluation and gated control of the radiotherapy through the motion estimation analysis before and after the therapy dose. Finally, the radiation-induced lung injury is introduced, which combines the previous two medical image processing and analysis steps with the features estimation and classification step. This framework estimates and combines both texture and functional features. The texture features are modeled using the novel 7th-order Markov Gibbs random field (MGRF) model that has the ability to accurately models the texture of healthy and injured lung tissues through simultaneously accounting for both vertical and horizontal relative dependencies between voxel-wise signals. While the functionality features calculations are based on the calculated deformation fields, obtained from the 4D-CT lung registration, that maps lung voxels between successive CT scans in the respiratory cycle. These functionality features describe the ventilation, the air flow rate, of the lung tissues using the Jacobian of the deformation field and the tissues’ elasticity using the strain components calculated from the gradient of the deformation field. Finally, these features are combined in the classification model to detect the injured parts of the lung at an early stage and enables an earlier intervention
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