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

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

Navigation system based in motion tracking sensor for percutaneous renal access

Tese de Doutoramento em Engenharia BiomédicaMinimally-invasive kidney interventions are daily performed to diagnose and treat several renal diseases. Percutaneous renal access (PRA) is an essential but challenging stage for most of these procedures, since its outcome is directly linked to the physician’s ability to precisely visualize and reach the anatomical target. Nowadays, PRA is always guided with medical imaging assistance, most frequently using X-ray based imaging (e.g. fluoroscopy). Thus, radiation on the surgical theater represents a major risk to the medical team, where its exclusion from PRA has a direct impact diminishing the dose exposure on both patients and physicians. To solve the referred problems this thesis aims to develop a new hardware/software framework to intuitively and safely guide the surgeon during PRA planning and puncturing. In terms of surgical planning, a set of methodologies were developed to increase the certainty of reaching a specific target inside the kidney. The most relevant abdominal structures for PRA were automatically clustered into different 3D volumes. For that, primitive volumes were merged as a local optimization problem using the minimum description length principle and image statistical properties. A multi-volume Ray Cast method was then used to highlight each segmented volume. Results show that it is possible to detect all abdominal structures surrounding the kidney, with the ability to correctly estimate a virtual trajectory. Concerning the percutaneous puncturing stage, either an electromagnetic or optical solution were developed and tested in multiple in vitro, in vivo and ex vivo trials. The optical tracking solution aids in establishing the desired puncture site and choosing the best virtual puncture trajectory. However, this system required a line of sight to different optical markers placed at the needle base, limiting the accuracy when tracking inside the human body. Results show that the needle tip can deflect from its initial straight line trajectory with an error higher than 3 mm. Moreover, a complex registration procedure and initial setup is needed. On the other hand, a real-time electromagnetic tracking was developed. Hereto, a catheter was inserted trans-urethrally towards the renal target. This catheter has a position and orientation electromagnetic sensor on its tip that function as a real-time target locator. Then, a needle integrating a similar sensor is used. From the data provided by both sensors, one computes a virtual puncture trajectory, which is displayed in a 3D visualization software. In vivo tests showed a median renal and ureteral puncture times of 19 and 51 seconds, respectively (range 14 to 45 and 45 to 67 seconds). Such results represent a puncture time improvement between 75% and 85% when comparing to state of the art methods. 3D sound and vibrotactile feedback were also developed to provide additional information about the needle orientation. By using these kind of feedback, it was verified that the surgeon tends to follow a virtual puncture trajectory with a reduced amount of deviations from the ideal trajectory, being able to anticipate any movement even without looking to a monitor. Best results show that 3D sound sources were correctly identified 79.2 ± 8.1% of times with an average angulation error of 10.4º degrees. Vibration sources were accurately identified 91.1 ± 3.6% of times with an average angulation error of 8.0º degrees. Additionally to the EMT framework, three circular ultrasound transducers were built with a needle working channel. One explored different manufacture fabrication setups in terms of the piezoelectric materials, transducer construction, single vs. multi array configurations, backing and matching material design. The A-scan signals retrieved from each transducer were filtered and processed to automatically detect reflected echoes and to alert the surgeon when undesirable anatomical structures are in between the puncture path. The transducers were mapped in a water tank and tested in a study involving 45 phantoms. Results showed that the beam cross-sectional area oscillates around the ceramics radius and it was possible to automatically detect echo signals in phantoms with length higher than 80 mm. Hereupon, it is expected that the introduction of the proposed system on the PRA procedure, will allow to guide the surgeon through the optimal path towards the precise kidney target, increasing surgeon’s confidence and reducing complications (e.g. organ perforation) during PRA. Moreover, the developed framework has the potential to make the PRA free of radiation for both patient and surgeon and to broad the use of PRA to less specialized surgeons.Intervenções renais minimamente invasivas são realizadas diariamente para o tratamento e diagnóstico de várias doenças renais. O acesso renal percutâneo (ARP) é uma etapa essencial e desafiante na maior parte destes procedimentos. O seu resultado encontra-se diretamente relacionado com a capacidade do cirurgião visualizar e atingir com precisão o alvo anatómico. Hoje em dia, o ARP é sempre guiado com recurso a sistemas imagiológicos, na maior parte das vezes baseados em raios-X (p.e. a fluoroscopia). A radiação destes sistemas nas salas cirúrgicas representa um grande risco para a equipa médica, aonde a sua remoção levará a um impacto direto na diminuição da dose exposta aos pacientes e cirurgiões. De modo a resolver os problemas existentes, esta tese tem como objetivo o desenvolvimento de uma framework de hardware/software que permita, de forma intuitiva e segura, guiar o cirurgião durante o planeamento e punção do ARP. Em termos de planeamento, foi desenvolvido um conjunto de metodologias de modo a aumentar a eficácia com que o alvo anatómico é alcançado. As estruturas abdominais mais relevantes para o procedimento de ARP, foram automaticamente agrupadas em volumes 3D, através de um problema de optimização global com base no princípio de “minimum description length” e propriedades estatísticas da imagem. Por fim, um procedimento de Ray Cast, com múltiplas funções de transferência, foi utilizado para enfatizar as estruturas segmentadas. Os resultados mostram que é possível detetar todas as estruturas abdominais envolventes ao rim, com a capacidade para estimar corretamente uma trajetória virtual. No que diz respeito à fase de punção percutânea, foram testadas duas soluções de deteção de movimento (ótica e eletromagnética) em múltiplos ensaios in vitro, in vivo e ex vivo. A solução baseada em sensores óticos ajudou no cálculo do melhor ponto de punção e na definição da melhor trajetória a seguir. Contudo, este sistema necessita de uma linha de visão com diferentes marcadores óticos acoplados à base da agulha, limitando a precisão com que a agulha é detetada no interior do corpo humano. Os resultados indicam que a agulha pode sofrer deflexões à medida que vai sendo inserida, com erros superiores a 3 mm. Por outro lado, foi desenvolvida e testada uma solução com base em sensores eletromagnéticos. Para tal, um cateter que integra um sensor de posição e orientação na sua ponta, foi colocado por via trans-uretral junto do alvo renal. De seguida, uma agulha, integrando um sensor semelhante, é utilizada para a punção percutânea. A partir da diferença espacial de ambos os sensores, é possível gerar uma trajetória de punção virtual. A mediana do tempo necessário para puncionar o rim e ureter, segundo esta trajetória, foi de 19 e 51 segundos, respetivamente (variações de 14 a 45 e 45 a 67 segundos). Estes resultados representam uma melhoria do tempo de punção entre 75% e 85%, quando comparados com o estado da arte dos métodos atuais. Além do feedback visual, som 3D e feedback vibratório foram explorados de modo a fornecer informações complementares da posição da agulha. Verificou-se que com este tipo de feedback, o cirurgião tende a seguir uma trajetória de punção com desvios mínimos, sendo igualmente capaz de antecipar qualquer movimento, mesmo sem olhar para o monitor. Fontes de som e vibração podem ser corretamente detetadas em 79,2 ± 8,1% e 91,1 ± 3,6%, com erros médios de angulação de 10.4º e 8.0 graus, respetivamente. Adicionalmente ao sistema de navegação, foram também produzidos três transdutores de ultrassom circulares com um canal de trabalho para a agulha. Para tal, foram exploradas diferentes configurações de fabricação em termos de materiais piezoelétricos, transdutores multi-array ou singulares e espessura/material de layers de suporte. Os sinais originados em cada transdutor foram filtrados e processados de modo a detetar de forma automática os ecos refletidos, e assim, alertar o cirurgião quando existem variações anatómicas ao longo do caminho de punção. Os transdutores foram mapeados num tanque de água e testados em 45 phantoms. Os resultados mostraram que o feixe de área em corte transversal oscila em torno do raio de cerâmica, e que os ecos refletidos são detetados em phantoms com comprimentos superiores a 80 mm. Desta forma, é expectável que a introdução deste novo sistema a nível do ARP permitirá conduzir o cirurgião ao longo do caminho de punção ideal, aumentado a confiança do cirurgião e reduzindo possíveis complicações (p.e. a perfuração dos órgãos). Além disso, de realçar que este sistema apresenta o potencial de tornar o ARP livre de radiação e alarga-lo a cirurgiões menos especializados.The present work was only possible thanks to the support by the Portuguese Science and Technology Foundation through the PhD grant with reference SFRH/BD/74276/2010 funded by FCT/MEC (PIDDAC) and by Fundo Europeu de Desenvolvimento Regional (FEDER), Programa COMPETE - Programa Operacional Factores de Competitividade (POFC) do QREN

Automatic Approach for Lung Segmentation with Juxta-Pleural Nodules from Thoracic CT Based on Contour Tracing and Correction

This paper presents a fully automatic framework for lung segmentation, in which juxta-pleural nodule problem is brought into strong focus. The proposed scheme consists of three phases: skin boundary detection, rough segmentation of lung contour, and pulmonary parenchyma refinement. Firstly, chest skin boundary is extracted through image aligning, morphology operation, and connective region analysis. Secondly, diagonal-based border tracing is implemented for lung contour segmentation, with maximum cost path algorithm used for separating the left and right lungs. Finally, by arc-based border smoothing and concave-based border correction, the refined pulmonary parenchyma is obtained. The proposed scheme is evaluated on 45 volumes of chest scans, with volume difference (VD) 11.15±69.63 cm3, volume overlap error (VOE) 3.5057±1.3719%, average surface distance (ASD) 0.7917±0.2741 mm, root mean square distance (RMSD) 1.6957±0.6568 mm, maximum symmetric absolute surface distance (MSD) 21.3430±8.1743 mm, and average time-cost 2 seconds per image. The preliminary results on accuracy and complexity prove that our scheme is a promising tool for lung segmentation with juxta-pleural nodules

Geometric Modeling of Thoracic Aortic Surface Morphology - Implications for Pathophysiology and Clinical Interventions

Vascular disease risk factors such as hypertension, hyperlipidemia and old age are all\ua0results of modern-day lifestyle, and these diseases are getting more and more common. One\ua0treatment option for vascular diseases such as aneurysms and dissections is endovascular\ua0aortic repair introduced in the early 1990s. This treatment uses tubular fabric covered\ua0metallic structures (endografts) that are implanted using a minimally invasive approach\ua0and placed to serve as an articial vessel in a damaged portion of the vasculature. To ensure\ua0that the interventions are successful, the endograft must be placed in the correct location,\ua0and designed to sustain the hostile biological, chemical, and mechanical conditions in the\ua0body for many years. This is an interaction that goes both ways, and keeping in mind\ua0that the endograft is a foreign object placed in the sensitive vascular system, it is also\ua0important that it does not disrupt the native conditions more than necessary.This thesis presents a segmentation and quantication methodology to accurately\ua0describe the complex morphology and motion of diseased blood vessels in vivo through a\ua0natural and intuitive description of their luminal surfaces. After methodology validation,\ua0a series of important clinical applications are performed, all based on non-invasive imaging.\ua0Firstly, it is shown that explicit surface curvature quantication is necessary when\ua0compared to relying solely on centerline curvature and estimation methods. Secondly, it is\ua0shown that endograft malapposition severity can be predicted from preoperative geometric\ua0analysis of thoracic aortic surfaces. Thirdly, a multiaxial dynamics analysis of cardiac\ua0induced thoracic aortic surface motion shows how thoracic endovascular aortic repair\ua0affects the deformations of the dierent portions of the thoracic aorta. Fourthly, the helical\ua0propagation pattern of type B aortic dissection is determined, and two distinct modes of\ua0chirality are revealed, i.e., achiral and right-handed chiral groups. Finally, the effects of\ua0thoracic endovascular aortic repair on helical and cross-sectional morphology of type B\ua0dissections are investigated revealing how acuity and chirality affects the alteration due to\ua0intraluminal lining with endografts. Thus, the work presented in this thesis contributes\ua0by adding knowledge about pathology and pathophysiology through better geometric\ua0description of surface conditions of diseased thoracic aortas. This gives clinicians insights\ua0to use in their treatment planning and provides more nuanced boundary conditions for\ua0endograft manufacturers. Comprehensive knowledge about diseases, better treatment\ua0planning, and better devices are all crucial in order to improve the outcomes of performed\ua0interventions and ultimately the quality of life for the treated patients

Study on the Method of Constructing a Statistical Shape Model and Its Application to the Segmentation of Internal Organs in Medical Images

In image processing, segmentation is one of the critical tasks for diagnostic analysis and image interpretation. In the following thesis, we describe the investigation of three problems related to the segmentation algorithms for medical images: Active shape model algorithm, 3-dimensional (3-D) statistical shape model building and organic segmentation experiments. For the development of Active shape models, the constraints of statistical model reduced this algorithm to be difficult for various biological shapes. To overcome the coupling of parameters in the original algorithm, in this thesis, the genetic algorithm is introduced to relax the shape limitation. How to construct a robust and effective 3-D point model is still a key step in statistical shape models. Generally the shape information is obtained from manually segmented voxel data. In this thesis, a two-step procedure for generating these models was designed. After transformed the voxel data to triangular polygonal data, in the first step, attitudes of these interesting objects are aligned according their surface features. We propose to reflect the surface orientations by means of their Gauss maps. As well the Gauss maps are mapped to a complex plane using stereographic projection approach. The experiment was run to align a set of left lung models. The second step is identifying the positions of landmarks on polygonal surfaces. This is solved by surface parameterization method. We proposed two simplex methods to correspond the landmarks. A semi-automatic method attempts to “copy” the phasic positions of pre-placed landmarks to all the surfaces, which have been mapped to the same parameterization domain. Another automatic corresponding method attempts to place the landmarks equidistantly. Finally, the goodness experiments were performed to measure the difference to manually corresponded results. And we also compared the affection to correspondence when using different surface mapping methods. The third part of this thesis is applying the segmentation algorithms to solve clinical problems. We did not stick to the model-based methods but choose the suitable one or their complex according to the objects. In the experiment of lung regions segmentation which includes pulmonary nodules, we propose a complementary region growing method to deal with the unpredictable variation of image densities of lesion regions. In the experiments of liver regions, instead of using region growing method in 3-D style, we turn into a slice-by-slice style in order to reduce the overflows. The image intensity of cardiac regions is distinguishable from lung regions in CT image. But as to the adjacent zone of heart and liver boundary are generally blurry. We utilized a shape model guided method to refine the segmentation results.3-D segmentation techniques have been applied widely not only in medical imaging fields, but also in machine vision, computer graphic. At the last part of this thesis, we resume some interesting topics such as 3-D visualization for medical interpretation, human face recognition and object grasping robot etc.九州工業大学博士学位論文 学位記番号:工博甲第353号　学位授与年月日:平成25年9月27日Chapter 1: Introduction|Chapter 2: Framework of Medical Image Segmentation|Chapter 3: 2-D Organic Regions Using Active Shape Model and Genetic Algorithm|Chapter 4: Alignment of 3-D Models|Chapter 5: Corespondence of 3-D Models|Chapter 6:Experiments of Organic Segmentation|Chapter 7: Visualization Technology and Its Applications|Chapter 8: Conclusions and Future Works九州工業大学平成25年

Improving Dose-Response Correlations for Locally Advanced NSCLC Patients Treated with IMRT or PSPT

The standard of care for locally advanced non-small cell lung cancer (NSCLC) is concurrent chemo-radiotherapy. Despite recent advancements in radiation delivery methods, the median survival time of NSCLC patients remains below 28 months. Higher tumor dose has been found to increase survival but also a higher rate of radiation pneumonitis (RP) that affects breathing capability. In fear of such toxicity, less-aggressive treatment plans are often clinically preferred, leading to metastasis and recurrence. Therefore, accurate RP prediction is crucial to ensure tumor coverage to improve treatment outcome. Current models have associated RP with increased dose but with limited accuracy as they lack spatial correlation between accurate dose representation and quantitative RP representation. These models represent lung tissue damage with radiation dose distribution planned pre-treatment, which assumes a fixed patient geometry and inevitably renders imprecise dose delivery due to intra-fractional breathing motion and inter-fractional anatomy response. Additionally, current models employ whole-lung dose metrics as the contributing factor to RP as a qualitative, binary outcome but these global dose metrics discard microscopic, voxel-(3D pixel)-level information and prevent spatial correlations with quantitative RP representation. To tackle these limitations, we developed advanced deformable image registration (DIR) techniques that registered corresponding anatomical voxels between images for tracking and accumulating dose throughout treatment. DIR also enabled voxel-level dose-response correlation when CT image density change (IDC) was used to quantify RP. We hypothesized that more accurate estimates of biologically effective dose distributions actually delivered, achieved through (a) dose accumulation using deformable registration of weekly 4DCT images acquired over the course or radiotherapy and (b) the incorporation of variable relative biological effectiveness (RBE), would lead to statistically and clinically significant improvement in the correlation of RP with biologically effective dose distributions. Our work resulted in a robust intra-4DCT and inter-4DCT DIR workflow, with the accuracy meeting AAPM TG-132 recommendations for clinical implementation of DIR. The automated DIR workflow allowed us to develop a fully automated 4DCT-based dose accumulation pipeline in RayStation (RaySearch Laboratories, Stockholm, Sweden). With a sample of 67 IMRT patients, our results showed that the accumulated dose was statistically different than the planned dose across the entire cohort with an average MLD increase of ~1 Gy and clinically different for individual patients where 16% resulted in difference in the score of the normal tissue complication probability (NTCP) using an established, clinically used model, which could qualify the patients for treatment planning re-evaluation. Lastly, we associated dose difference with accuracy difference by establishing and comparing voxel-level dose-IDC correlations and concluded that the accumulated dose better described the localized damage, thereby a closer representation of the delivered dose. Using the same dose-response correlation strategy, we plotted the dose-IDC relationships for both photon patients (N = 51) and proton patients (N = 67), we measured the variable proton RBE values to be 3.07–1.27 from 9–52 Gy proton voxels. With the measured RBE values, we fitted an established variable proton RBE model with pseudo-R2 of 0.98. Therefore, our results led to statistically and clinically significant improvement in the correlation of RP with accumulated and biologically effective dose distributions and demonstrated the potential of incorporating the effect of anatomical change and biological damage in RP prediction models

Reproducibility Study of Tumor Biomarkers Extracted from Positron Emission To-mography Images with 18F-Fluorodeoxyglucose

Introduction and aim Cancer is one of the main causes of death worldwide. Tumor diagnosis, staging, surveillance, prognosis and access to the response to therapy are critical when it comes to plan and analyze the optimal treatment strategies of cancer diseases. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) imaging has provided some reliable prognostic factors in several cancer types, by extracting quantitative measures from the images obtained in clinics. The recent addition of digital equipment to the clinical armamentarium of PET leads to some concerns regarding inter-device data variability. Consequently, the reproducibility assess-ment of the tumor features, usually used in clinics and research, extracted from images acquired in an analog and new digital PET equipment is of paramount importance for use of multi-scanner studies in longitudinal patient’s studies. The aim of this study was to evaluate the inter-equipment reliability of a set of 25 lesional features commonly used in clinics and research. Material and methods In order to access the features agreement, a dual imaging protocol was designed. Whole-body 18F-FDG PET images from 53 oncological patients were acquired, after a single 18F-FDG injection, with two devices alternatively: Philips Vereos Digital PET/CT (VE-REOS with three different reconstruction protocols- digital) and Philips GEMINI TF-16 (GEM-INI with single standard reconstruction protocol- analog). A nuclear medicine physician identi-fied 283 18F-FDG avid lesions. Then, all lesions (both equipment) were automatically segmented based on a Bayesian classifier optimized to this study. In the total, 25 features (first order statistics and geometric features) were computed and compared. The intraclass correlation coefficient (ICC) was used as measure of agreement. Results A high agreement (ICC > 0.75) was obtained for most of the lesion features pulled out from both devices imaging data, for all (GEMINI vs VEREOS) reconstructions. The lesion fea-tures most frequently used, maximum standardized uptake value, metabolic tumor volume, and total lesion glycolysis reached maximum ICC of 0.90, 0.98 and 0.97, respectively. Conclusions Under controlled acquisition and reconstruction parameters, most of the features studied can be used for research and clinical work, whenever multiple scanner (e.g. VEREOS and GEMINI) studies, mainly during longitudinal patient evaluation, are used