Anthropometric and genetic determinants of cardiac morphology and function

Background Cardiac structure and function result from complex interactions between genetic and environmental factors. Population-based studies have relied on 2-dimensional cardiovascular magnetic resonance as the gold-standard for phenotyping. However, this technique provides limited global metrics and is insensitive to regional or asymmetric changes in left ventricular (LV) morphology. High-resolution 3-dimensional cardiac magnetic resonance (3D-CMR) with computational quantitative phenotyping, might improve on traditional CMR by enabling the creation of detailed 3D statistical models of the variation in cardiac phenotypes for use in studies of genetic and/or environmental effects on cardiac form or function. Purpose To determine whether 3D-CMR is applicable at scale, and provides methodological and statistical advantages over conventional imaging for large-scale population studies and to apply 3D-CMR to anthropometric and genetic studies of the heart. Methods 1530 volunteers (54.8% females, 74.7% Caucasian, mean age 41.3±13.0 years) without self-reported cardiovascular disease were recruited prospectively to the Digital Heart Project. Using a cardiac atlas-based software, these images were computationally processed and quantitatively analysed. Parameters such as myocardial shape, curvature, wall thickness, relative wall thickness, end-systolic wall stress, fractional wall thickening and ventricular volumes were extracted at over 46,000 points in the model. The relationships between these parameters and systolic blood pressure (SBP), fat mass, lean mass and genetic variationswere analysed using 3D regression models adjusted for body surface area, gender, race, age and multiple testing. Targeted resequencing of titin (TTN), the largest human gene and the commonest genetic cause of dilated cardiomyopathy, was performed in 928 subjects while common variants (~700.000) were genotyped in 1346 subjects. Results Automatically segmented 3D images were more accurate than 2D images at defining cardiac surfaces, resulting in fewer subjects being required to detect a statistically significant 1 mm difference in wall thickness. 3D-CMR enabled the detection of a strong and distinct regionality of the effects of SBP, body composition and genetic variation on the heart. It shows that the precursors of the hypertensive heart phenotype can be traced to healthy normotensives and that different ratios of body composition are associated with particular gender-specific patterns of cardiac remodelling. In 17 asymptomatic subjects with genetic variations associated with dilated cardiomyopathy, early stages of ventricular impairment and wall thinning were identified, which were not apparent by 2D imaging. Conclusions 3D-CMR combined with computational modelling provides high-resolution insight into the earliest stages of heart disease. These methods show promise for population-based studies of the anthropometric, environmental and genetic determinants of LV form and function in health and disease.Open Acces

Development of motion compensated 3D T2 mapping for cardiac imaging

Tese de mestrado integrado, Engenharia Biomédica e Biofísica (Engenharia Clínica e Instrumentação Médica)Universidade de Lisboa, Faculdade de Ciências, 2015A Ressonância Magnética Cardíaca (RMC) tem vindo a crescer tendo-se tornado numa excelente técnica de avaliação de doenças cardíacas, uma vez que produz imagens do coração de alta qualidade e de forma não ionizante. O edema do miocárdio é uma patologia em que ocorre aumento da quantidade de água o que se traduz num valor de T2 mais elevado nos tecidos. Para além do edema, outras patologias que levam a um aumento do valor do T2 são por exemplo o enfarte agudo do miocárdio, miocardite, tecidos transplantados rejeitados ou a sarcoidose. Por outro lado, valores de T2 mais baixos já foram encontrados em hemorragias no interior do miocárdio e em excessos crónicos de ferro em cardiomiopatias de ferritina. Esta relação faz com que o T2 e, portanto, as imagens ponderadas em T2 sejam bastante úteis em RMC. No entanto, as imagens de RMC ponderadas em T2 normalmente apresentam limitações: são bastante sensíveis a movimentos dos órgãos, o sangue pode afetar o sinal medido nos tecidos e estas imagens estão sempre sujeitas a uma interpretação subjetiva por parte do médico. Assim sendo, recentemente foi proposta uma alternativa mais quantitativa, que foi denominada de mapeamento de T2. Normalmente, este método envolve a aquisição de três sequencias T2prep, cada uma com diferentes tempos de eco do T2prep. O sinal em cada imagem representa um diferente tempo de eco ao longo da curva de decaimento em T2 e os mapas gerados são baseados nas três imagens com diferentes ponderações em T2. Os mapeamentos de T2 podem fornecer uma deteção exata e confiável do tecido edematoso, presente no miocárdio, superando as limitações inerentes à análise de imagens ponderadas em T2. Contudo, as técnicas mais comuns de mapeamento de T2 ainda apresentam algumas limitações como a baixa resolução espacial e a incapacidade de corrigir corretamente o movimento, levando a que a maioria dos mapeamentos de T2 seja feita a duas-dimensões (2D) { ou seja apenas um corte { e em apneia. No entanto, apneias incompletas podem-se traduzir num mau co-registo das diferentes imagens, originando mapas incorretos. Na prática, longas aquisições e varias apneias são um entrave a mapeamentos de T2 de todo o coração { e não apenas só ao ventrículo esquerdo. Por exemplo, em situações onde o edema do miocárdio possa servir como um marcador de isquémia aguda (associada a dor torácica), certos pacientes têm dificuldade em tolerar múltiplas apneias e em permanecer longos tempos de aquisição dentro do magneto. Além disso, a maioria dos mapeamentos de T2 presentes na literatura foram testados e planeados para equipamentos de 1.5T. Paralelamente, têm sido utilizadas algumas técnicas para limitar o efeito do movimento respiratório durante as aquisições das imagens { denominadas de navegadores. O navegador diafragmático a uma-dimensão (d1D NAV) { também denominado por pencil beam { é a abordagem mais simples e baseia-se numa relação linear entre o diafragma e o movimento respiratório. No entanto, para além do planeamento que é necessário antes da aquisição das imagens { de modo a colocar o navegador perto do diafragma { é também difícil de prever o tempo extra que esta abordagem vai implicar, uma vez que esta técnica é pouco eficiente para ciclos respiratórios e cardíacos irregulares. Estas limitações levaram a que um tipo de navegador diferente fosse criado, ao qual se chamou auto-navegação. Com esta abordagem o movimento respiratório é calculado diretamente a partir dos dados, removendo a necessidade de um modelo de movimento do diafragma. No entanto, esta técnica pode incluir na estimativa do movimento dos pulmões alguns tecidos estáticos (como por exemplo a parede torácica), o que pode levar a uma incorreta estimativa do movimento. Muito recentemente, uma nova técnica foi proposta { e foi utilizada neste trabalho incorporada na sequência utilizada para obter os mapeamentos de T2 { chamada de navegação baseada em imagem (iNAV). Com o iNAV, antes da aquisição principal, são obtidas imagens do coração de baixa resolução. Estas imagens de baixa resolução são utilizadas para automaticamente e em tempo real, calcular o movimento do coração. Este calculo do movimento do coração, é feito através de um algoritmo { adaptado de uma versão previamente existente { que utiliza a informação das imagens de baixa resolução e separa os tecidos em movimento dos tecidos estáticos levando a uma estimativa precisa do movimento respiratório. O trabalho aqui apresentado consistiu no desenvolvimento, teste e validação de uma nova abordagem para o mapeamento de T2 que permite a aquisição de um volume a três-dimensões (3D) cobrindo assim todo o coração. A esta abordagem, foi englobado o iNAV, que reduz drasticamente o tempo de aquisição, permitindo que o sujeito possa respirar livremente durante a realização do exame. Sendo a sua é ciência de 100% é possível prever o tempo esperado para o exame. Apesar de outros navegadores (como por exemplo o pencil beam e a auto-navegação) já terem sido utilizados para melhorar o mapeamento de T2, não existem estudos que tenham recorrido ao iNAV. É de realçar ainda o facto de se usar um impulso de saturação, fazendo com que esta abordagem seja insensível a variações na frequência cardíaca e permitindo que sejam adquiridas imagens em todos os batimentos cardíacos, não sendo necessário esperar muito tempo para recuperar a magnetização T1. Outra das vantagens da sequência apresentada é o facto de as imagens se encontrarem espacialmente alinhadas usando volumes intercalados com diferentes ponderações em T2. As aquisições a 3D melhoram quer a compensação do movimento através dos vários planos quer a razão sinal-ruído (RSR) em comparação com técnicas anteriores. A precisão desta técnica foi medida usando fantomas de gel com diferentes valores de T1 e T2 e foi demonstrada em aquisições a 3D para mapeamento de T2 do coração em humanos saudáveis (isto é, sem nenhuma patologia cardíaca) num equipamento de 3T. Para se proceder à validação desta abordagem foram comparados os resultados dos mapeamentos de T2 utilizando a correção do movimento feita pelo iNAV e através do pencil beam. Finalmente, foi feita a análise estatística para comparar os resultados obtidos. Os mapeamentos de T2 a 3D revelaram resultados consistentes com os métodos mais tradicionais no caso dos voluntários analisados. O valor de T2 obtido para o miocárdio foi de 45.7 ± 5.7 ms utilizando a técnica desenvolvida neste trabalho (tempo de aquisição = 4.56 ± 1.7 min), 47.1 ± 8.9 ms utilizando a correção feita pelo pencil beam (tempo de scan = 14.2 ± 3 min) e 46.1 ± 6.3 ms numa aquisição a 2D e em apneia. Após a análise estatística, conclui-se que os valores de T2 não apresentam diferenças significativas entre métodos (p < 0.05). A técnica desenvolvida neste trabalho permite obter mapeamentos de T2 a 3D do coração de forma precisa e em menos de 5 minutos. Além disso, esta abordagem permite que o paciente respire livremente aquando da aquisição das imagens e apresenta resultados similares aos que se obtém com a abordagem a duas dimensões. Apesar de não ter sido possível testar a técnica proposta em pacientes, acredita-se que é possível utiliza-la sem qualquer restrição. Trabalhos futuros podem incluir o teste deste método na caracterização de diferentes patologias cardíacas, bem como na tentativa de combinar a técnica aqui proposta com métodos de aquisição paralela, que permitam reduzir ainda mais o tempo de scan. É possível concluir que os objetivos foram atingidos e os resultados bastante promissores nesta abordagem inovadora, uma vez que não há registos de mapeamentos de T2 juntamente com o iNAV.Purpose: T2 mapping can detect variations in the water content of the myocardium. As it consists of a quantitative approach, this technique overcame some of the limitations present in the commonly used T2-weighted MRI. In fact, this type of methodology is becoming increasingly important for tissue characterization in patients with myocardial pathologies (e.g. myocardial edema). As a large set of images may be needed to calculate each parameter, scans have been typically limited to 2D images acquired during breath-holding (BH). The aim of this project was to extend the commonly used breath hold approaches enabling free breathing while attaining high resolution whole heart images by developing and test a free-breathing, whole heart T2 mapping technique at 3.0T. Methods: To generate T2 maps, multiple images are acquired with varying degrees of T2 weighting using magnetization preparation. In this work, imagebased navigation (iNAV) was combined with a dynamic T2 prepared sequence with a varying T2prep echo time to investigate the feasibility of iNAV for T2 mapping with 100% scan efficiency. ECG-triggering, interleaved acquisitions and a saturation pulse { to reset the magnetization on every heartbeat { were used in the module. A monoexponential function is adjusted to the images intensities and with the fitting the T2 maps are generated. The work consisted in adapting the MRI pulse sequence for T2 mapping by introducing iNAV for respiratory motion correction and evaluation of the new 3D T2mapping scan in phantoms as well as healthy subjects. Results: In healthy volunteers the T2 values did not display significant differences (p < 0.05) when the results obtained with the proposed approach (45.7 ± 5.7 ms), were compared to those obtained with previous methods - the 3D T2prep corrected with the pencil beam navigator (47.1 ± 8.9 ms) and the breath-held 2D T2prep (46.1 ± 6.3 ms). Conclusion: The proposed free-breathing whole heart 3D T2 mapping approach is feasible and can be performed within less than 5 min with similar accuracy to that of the 2D-BH T2 mapping approach. Also, it may be applicable in myocardial assessment instead of current clinical black blood sequences

MR imaging of left-ventricular function : novel image acquisition and analysis techniques.

Many cardiac diseases, such as myocardial ischemia, secondary to coronary artery disease, may be identified and localized through the analysis of cardiac deformations. Early efforts for quantifying ventricular wall motion used surgical implantation and tracking of radiopaque markers with X-ray imaging in canine hearts [1]. Such techniques are invasive and affect the regional motion pattern of the ventricular wall during the marker tracking process and, clearly are not feasible clinically. Noninvasive imaging techniques are vital and have been widely applied to the clinic. MRI is a noninvasive imaging technique with the capability to monitor and assess the progression of cardiovascular diseases (CVD) so that effective procedures for the care and treatment of patients can be developed by physicians and researchers. It is capable of providing 3D analysis of global and regional cardiac function with great accuracy and reproducibility. In the past few years, numerous efforts have been devoted to cardiac motion recovery and deformation analysis from MR imaging sequences. In order to assess cardiac function, there are two categories of indices that are used: global and regional indices. Global indices include ejection fraction, cavity volume, and myocardial mass [2]. They are important indices for cardiac disease diagnosis. However, these global indices are not specific for regional analysis. A quantitative assessment of regional parameters may prove beneficial for the diagnosis of disease and evaluation of severity and the quantification of treatment [3]. Local measures, such as wall deformation and strain in all regions of the heart, can provide objective regional quantification of ventricular wall function and relate to the location and extent of ischemic injury. This dissertation is concerned with the development of novel MR imaging techniques and image postprocessing algorithms to analyze left ventricular deformations. A novel pulse sequence, termed Orthogonal CSPAMM (OCSPAMM), has been proposed which results in the same acquisition time as SPAMM for 2D deformation estimation while keeping the main advantages of CSPAMM [4,5]: i.e., maintaining tag contrast through-out the ECG cycle. Different from CSPAMM, in OCSPAMM the second tagging pulse orientation is rotated 90 degrees relative to the first one so that motion information can be obtained simultaneously in two directions. This reduces the acquisition time by a factor of two as compared to the traditional CSPAMM, in which two separate imaging sequences are applied per acquisition. With the application of OCSPAMM, the effect of tag fading encountered in SPAMM tagging due to Tl relaxation is mitigated and tag deformations can be visualized for the entire cardiac cycle, including diastolic phases. A multilevel B-spline fitting method (MBS) has been proposed which incorporates phase-based displacement information for accurate calculation of 2D motion and strain from tagged MRI [6, 7]. The proposed method combines the advantages of continuity and smoothness of MBS, and makes use of phase information derived from tagged MR images. Compared to previous 2D B-spline-based deformation analysis methods, MBS has the following advantages: 1) It can simultaneously achieve a smooth deformation while accurately approximating the given data set; 2) Computationally, it is very fast; and 3) It can produce more accurate deformation results. Since the tag intersections (intersections between two tag lines) can be extracted accurately and are more or less distributed evenly over the myocardium, MBS has proven effective for 2D cardiac motion tracking. To derive phase-based displacements, 2D HARP and SinMod analysis techniques [8,9] were employed. By producing virtual tags from HARP /SinMod and calculating intersections of virtual tag lines, more data points are obtained. In the reference frame, virtual tag lines are the isoparametric curves of an undeformed 2D B-spline model. In subsequent frames, the locations of intersections of virtual tag lines over the myocardium are updated with phase-based displacement. The advantage of the technique is that in acquiring denser myocardial displacements, it uses both real and virtual tag line intersections. It is fast and more accurate than 2D HARP and SinMod tracking. A novel 3D sine wave modeling (3D SinMod) approach for automatic analysis of 3D cardiac deformations has been proposed [10]. An accelerated 3D complementary spatial modulation of magnetization (CSPAMM) tagging technique [11] was used to acquire complete 3D+t tagged MR data sets of the whole heart (3 dynamic CSPAMM tagged MRI volume with tags in different orientations), in-vivo, in 54 heart beats and within 3 breath-holds. In 3D SinMod, the intensity distribution around each pixel is modeled as a cosine wave front. The principle behind 3D SinMod tracking is that both phase and frequency for each voxel are determined directly from the frequency analysis and the displacement is calculated from the quotient of phase difference and local frequency. The deformation fields clearly demonstrate longitudinal shortening during systole. The contraction of the LV base towards the apex as well as the torsional motion between basal and apical slices is clearly observable from the displacements. 3D SinMod can automatically process the image data to derive measures of motion, deformations, and strains between consecutive pair of tagged volumes in 17 seconds. Therefore, comprehensive 4D imaging and postprocessing for determination of ventricular function is now possible in under 10 minutes. For validation of 3D SinMod, 7 3D+t CSPAMM data sets of healthy subjects have been processed. Comparison of mid-wall contour deformations and circumferential shortening results by 3D SinMod showed good agreement with those by 3D HARP. Tag lines tracked by the proposed technique were also compared with manually delineated ones. The average errors calculated for the systolic phase of the cardiac cycles were in the sub-pixel range

Reproducibility of Hyperpolarized Xenon-129 Magnetic Resonance Imaging

Spirometry and plethysmography provide gold standard measurements of obstructive lung disease, although these are global measurements of lung function made at the mouth, of a highly regionally heterogeneous disease. Hyperpolarized 129Xe magnetic resonance imaging (MRI) is a non-invasive, non-radiation-based imaging tool for visualizing regional lung structure and function. However, the reproducibility of 129Xe MRI measurements has not yet been studied or determined. Hence, in this thesis, we evaluated the reproducibility of 129Xe MRI using quantitative measurements such as ventilation defect percent (VDP). We showed that 129Xe VDP had high intra-observer and inter-observer reproducibility for repeated scans acquired on the same-day and after 1-week and its reproducibility was comparable to that of 3He VDP. 129Xe VDP showed strong and significant correlations with pulmonary function tests. These results suggested that 129Xe VDP is reproducible over short periods of time and can be a reliable measurement to study pulmonary function in imaging studies

Improved 3D MR Image Acquisition and Processing in Congenital Heart Disease

Congenital heart disease (CHD) is the most common type of birth defect, affecting about 1% of the population. MRI is an essential tool in the assessment of CHD, including diagnosis, intervention planning and follow-up. Three-dimensional MRI can provide particularly rich visualization and information. However, it is often complicated by long scan times, cardiorespiratory motion, injection of contrast agents, and complex and time-consuming postprocessing. This thesis comprises four pieces of work that attempt to respond to some of these challenges. The first piece of work aims to enable fast acquisition of 3D time-resolved cardiac imaging during free breathing. Rapid imaging was achieved using an efficient spiral sequence and a sparse parallel imaging reconstruction. The feasibility of this approach was demonstrated on a population of 10 patients with CHD, and areas of improvement were identified. The second piece of work is an integrated software tool designed to simplify and accelerate the development of machine learning (ML) applications in MRI research. It also exploits the strengths of recently developed ML libraries for efficient MR image reconstruction and processing. The third piece of work aims to reduce contrast dose in contrast-enhanced MR angiography (MRA). This would reduce risks and costs associated with contrast agents. A deep learning-based contrast enhancement technique was developed and shown to improve image quality in real low-dose MRA in a population of 40 children and adults with CHD. The fourth and final piece of work aims to simplify the creation of computational models for hemodynamic assessment of the great arteries. A deep learning technique for 3D segmentation of the aorta and the pulmonary arteries was developed and shown to enable accurate calculation of clinically relevant biomarkers in a population of 10 patients with CHD

Analysis of first pass myocardial perfusion imaging with magnetic resonance

Early diagnosis and localisation of myocardial perfusion defects is an important step in the treatment of coronary artery disease. Thus far, coronary angiography is the conventional standard investigation for patients with known or suspected coronary artery disease and it provides information about the presence and location of coronary stenoses. In recent years, the development of myocardial perfusion CMR has extended the role of MR in the evaluation of ischaemic heart disease beyond the situations where there have already been gross myocardial changes such as acute infarction or scarring. The ability to non-invasively evaluate cardiac perfusion abnormalities before pathologic effects occur, or as follow-up to therapy, is important to the management of patients with coronary artery disease. Whilst limited multi-slice 2D CMR perfusion studies are gaining increased clinical usage for quantifying gross ischaemic burden, research is now directed towards complete 3D coverage of the myocardium for accurate localisation of the extent of possible defects. In 3D myocardial perfusion imaging, a complete volumetric data set has to be acquired for each cardiac cycle in order to study the first pass of the contrast bolus. This normally requires a relatively large acquisition window within each cardiac cycle to ensure a comprehensive coverage of the myocardium and reasonably high resolution of the images. With multi-slice imaging, long axis cardiac motion during this large acquisition window can cause the myocardium imaged in different cross- sections to be mis-registered, i.e., some part of the myocardium may be imaged more than twice whereas other parts may be missed out completely. This type of mis-registration is difficult to correct for by using post-processing techniques. The purpose of this thesis is to investigate techniques for tracking through plane motion during 3D myocardial perfusion imaging, and a novel technique for extracting intrinsic relationships between 3D cardiac deformation due to respiration and multiple ID real-time measurable surface intensity traces is developed. Despite the fact that these surface intensity traces can be strongly coupled with each other but poorly correlated with respiratory induced cardiac deformation, we demonstrate how they can be used to accurately predict cardiac motion through the extraction of latent variables of both the input and output of the model. The proposed method allows cross-modality reconstruction of patient specific models for dense motion field prediction, which after initial modelling can be use in real-time prospective motion tracking or correction. In CMR, new imaging sequences have significantly reduced the acquisition window whilst maintaining the desired spatial resolution. Further improvements in perfusion imaging will require the application of parallel imaging techniques or making full use of the information content of the ¿-space data. With this thesis, we have proposed RR-UNFOLD and RR-RIGR for significantly reducing the amount of data that is required to reconstruct the perfusion image series. The methods use prospective diaphragmatic navigator echoes to ensure UNFOLD and RIGR are carried out on a series of images that are spatially registered. An adaptive real-time re-binning algorithm is developed for the creation of static image sub-series related to different levels of respiratory motion. Issues concerning temporal smoothing of tracer kinetic signals and residual motion artefact are discussed, and we have provided a critical comparison of the relative merit and potential pitfalls of the two techniques. In addition to the technical and theoretical descriptions of the new methods developed, we have also provided in this thesis a detailed literature review of the current state-of-the-art in myocardial perfusion imaging and some of the key technical challenges involved. Issues concerning the basic background of myocardial ischaemia and its functional significance are discussed. Practical solutions to motion tracking during imaging, predictive motion modelling, tracer kinetic modelling, RR-UNFOLD and RR-RIGR are discussed, all with validation using patient and normal subject data to demonstrate both the strength and potential clinical value of the proposed techniques.Open acces

Myocardial fibrosis in repaired tetralogy of Fallot; Predicting ventricular arrhythmia and sudden cardiac death

We are faced with new challenges in the growing population of adult survivors with repaired tetralogy of Fallot (rTOF). The risk of premature death persists and drives eager pursuit for the accurate identification of patients at high-risk of malignant ventricular tachycardia (VT) and sudden cardiac death (SCD). It is previously known that inducible VT predicts mortality in rTOF patients. We show that the burden of right ventricular (RV) late gadolinium enhancement (LGE) defined fibrosis > 25cm3 quantified by high-sensitivity 3D LGE can predict inducible VT as a proxy endpoint for mortality. Patients with minimal RV LGE < 10cm3 were extremely unlikely to have inducible VT suggesting those with minimal RVLGE avoid an invasive study. In a prospective study of 550 rTOF patients, a high-risk subgroup of patients with a 4.4% annualised risk of death and 3.7% annualised risk of life-threatening VT/SCD were identified. RVLGE was a strong predictor of outcome. We demonstrated how RVLGE can be integrated with other independent predictors into weighted risk scores ready for clinical use. Diffuse fibrosis defined by RV T1 shows promise as a subtle biomarker of adverse remodelling. An imbalance in the expression of fibrosis biomarkers suggests that a state of high-collagen turnover exists and correlates with adverse remodelling. In conclusion, myocardial fibrosis plays a central role in predicting death and malignant VT in rTOF. This work identifies biomarkers to help risk stratify and enable more personalised and targeted care in the life-long follow up of adult rTOF patients.Open Acces

Pulmonary Image Segmentation and Registration Algorithms: Towards Regional Evaluation of Obstructive Lung Disease

Pulmonary imaging, including pulmonary magnetic resonance imaging (MRI) and computed tomography (CT), provides a way to sensitively and regionally measure spatially heterogeneous lung structural-functional abnormalities. These unique imaging biomarkers offer the potential for better understanding pulmonary disease mechanisms, monitoring disease progression and response to therapy, and developing novel treatments for improved patient care. To generate these regional lung structure-function measurements and enable broad clinical applications of quantitative pulmonary MRI and CT biomarkers, as a first step, accurate, reproducible and rapid lung segmentation and registration methods are required. In this regard, we first developed a 1H MRI lung segmentation algorithm that employs complementary hyperpolarized 3He MRI functional information for improved lung segmentation. The 1H-3He MRI joint segmentation algorithm was formulated as a coupled continuous min-cut model and solved through convex relaxation, for which a dual coupled continuous max-flow model was proposed and a max-flow-based efficient numerical solver was developed. Experimental results on a clinical dataset of 25 chronic obstructive pulmonary disease (COPD) patients ranging in disease severity demonstrated that the algorithm provided rapid lung segmentation with high accuracy, reproducibility and diminished user interaction. We then developed a general 1H MRI left-right lung segmentation approach by exploring the left-to-right lung volume proportion prior. The challenging volume proportion-constrained multi-region segmentation problem was approximated through convex relaxation and equivalently represented by a max-flow model with bounded flow conservation conditions. This gave rise to a multiplier-based high performance numerical implementation based on convex optimization theories. In 20 patients with mild- to-moderate and severe asthma, the approach demonstrated high agreement with manual segmentation, excellent reproducibility and computational efficiency. Finally, we developed a CT-3He MRI deformable registration approach that coupled the complementary CT-1H MRI registration. The joint registration problem was solved by exploring optical-flow techniques, primal-dual analyses and convex optimization theories. In a diverse group of patients with asthma and COPD, the registration approach demonstrated lower target registration error than single registration and provided fast regional lung structure-function measurements that were strongly correlated with a reference method. Collectively, these lung segmentation and registration algorithms demonstrated accuracy, reproducibility and workflow efficiency that all may be clinically-acceptable. All of this is consistent with the need for broad and large-scale clinical applications of pulmonary MRI and CT